Trial Outcomes & Findings for Treatment of Rett Syndrome With Recombinant Human IGF-1 (NCT NCT01777542)

Last Updated: 2018-03-26

Results Overview

The RSBQ is an informant/parent-completed measure of abnormal behaviors typically observed in individuals with RTT, which is completed by a parent/caregiver/LAR. Each item, grouped into eight domains/factors: General mood, Breathing problems, Body rocking and expressionless face, Hand behaviors, Repetitive face movements, Night-time behaviors, Fear/anxiety and Walking/standing), is scored on a Likert scale of 0-2, according to how well the item describes the individual's behavior. A score of "0" indicates the described item is "not true," a score of "1" indicates the described item is "somewhat or sometimes true," and a score of "2" indicates the described item is "very true or often true." The total sum of items in each subscale is reported. For the fear/anxiety subscale, the sum total could be between 0-8. The higher the sum total score, the greater the frequency of fear/anxiety behaviors.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Results posted on

2018-03-26

Participant Flow

Assessments findings during the Screening Visit that could result in ineligibility after informed consent include: 1. Scoliosis curve \> 40º by x-ray 2. Bone age \> 11 years by x-ray 3. Cardiomegaly by echocardiogram 4. Tanner Stage II breast development by physical exam 5. Prolonged QTc by ECG

Participant milestones

Participant milestones
Measure	Placebo First, Then rhIGF-1 One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
First Intervention (20 Weeks) STARTED	15	15
First Intervention (20 Weeks) COMPLETED	15	15
First Intervention (20 Weeks) NOT COMPLETED	0	0
Washout Period (28 +/- 2 Weeks) STARTED	15	15
Washout Period (28 +/- 2 Weeks) COMPLETED	15	15
Washout Period (28 +/- 2 Weeks) NOT COMPLETED	0	0
Second Intervention (20 Weeks) STARTED	15	15
Second Intervention (20 Weeks) COMPLETED	15	14
Second Intervention (20 Weeks) NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo First, Then rhIGF-1 One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Second Intervention (20 Weeks) Adverse Event	0	1

Baseline Characteristics

Treatment of Rett Syndrome With Recombinant Human IGF-1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=30 Participants All 30 subjects enrolled and randomized in the study
Age, Categorical <=18 years	30 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Population: In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Visit 1 - First Intervention	4.00 units on a scale Interval 3.0 to 6.0	5.00 units on a scale Interval 2.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Visit 2 - First Intervention	5.00 units on a scale Interval 3.0 to 6.0	3.00 units on a scale Interval 2.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Visit 3 - First Intervention	4.00 units on a scale Interval 3.0 to 5.0	3.00 units on a scale Interval 2.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Visit 4 - First Intervention	4.00 units on a scale Interval 2.0 to 5.0	3.00 units on a scale Interval 1.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Visit 5 - First Intervention	3.00 units on a scale Interval 2.0 to 5.0	3.00 units on a scale Interval 1.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Visit 6 - Second Intervention	4.00 units on a scale Interval 2.0 to 5.0	4.00 units on a scale Interval 2.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Visit 7 - Second Intervention	4.00 units on a scale Interval 2.0 to 4.0	3.00 units on a scale Interval 2.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Visit 8 - Second Intervention	3.00 units on a scale Interval 3.0 to 5.0	4.00 units on a scale Interval 1.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Visit 9 - Second Intervention	3.00 units on a scale Interval 2.0 to 4.0	3.00 units on a scale Interval 1.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Visit 10 - Second Intervention	4.00 units on a scale Interval 2.0 to 5.0	3.00 units on a scale Interval 2.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale Follow-up	3.50 units on a scale Interval 2.0 to 5.0	3.50 units on a scale Interval 2.0 to 5.0

PRIMARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Population: In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

The ADAMS is completed by the parent/caregiver/LAR and consists of 29 items which are scored on a 4-point rating scale that combines frequency and severity ratings. The instructions ask the rater to describe the individual's behavior over the last six months on the following scale: "0" if the behavior has not occurred, "1" if the behavior occurs occasionally or is a mild problem, "2" if the behavior occurs quite often or is moderate problem, or "3" if the behavior occurs a lot or is a severe problem. The Social Avoidance subscale of the ADAMS will be used as a primary outcome measure for this trial. The range for this subscale is 0-21. The higher the subscale score, the more problematic the behavior.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Visit 1 - First Intervention	6.00 units on a scale Interval 5.0 to 8.0	4.00 units on a scale Interval 2.0 to 8.0
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Visit 2 - First Intervention	5.00 units on a scale Interval 3.0 to 7.0	5.00 units on a scale Interval 3.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Visit 3 - First Intervention	5.00 units on a scale Interval 4.0 to 7.0	4.00 units on a scale Interval 2.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Visit 4 - First Intervention	6.00 units on a scale Interval 3.0 to 7.0	4.00 units on a scale Interval 3.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Visit 5 - First Intervention	5.00 units on a scale Interval 2.0 to 6.0	3.00 units on a scale Interval 2.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Visit 6 - Second Intervention	4.00 units on a scale Interval 3.0 to 5.0	4.00 units on a scale Interval 3.0 to 6.0
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Visit 7 - Second Intervention	4.00 units on a scale Interval 2.0 to 7.0	4.00 units on a scale Interval 3.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Visit 8 - Second Intervention	4.00 units on a scale Interval 2.0 to 6.0	4.00 units on a scale Interval 3.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Visit 9 - Second Intervention	3.00 units on a scale Interval 1.0 to 7.0	3.00 units on a scale Interval 2.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Visit 10 - Second Intervention	3.50 units on a scale Interval 2.0 to 5.0	3.50 units on a scale Interval 2.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale Follow-up	4.00 units on a scale Interval 2.0 to 6.0	3.00 units on a scale Interval 2.0 to 4.0

PRIMARY outcome

Timeframe: Every 10 weeks during each of the two 20-week treatment periods

Population: One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

This scale is used to judge the severity of the subject's disease prior to entry into the study. The clinician will rate the severity of behavioral symptoms at baseline on a 7-point scale from not impaired to the most impaired. The scores that correspond to each possible grouping are as follows: 1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired. The possible range for reported scores is 1-7.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Clinical Global Impression - Severity (CGI-S) Visit 1 - First Intervention	4.00 units on a scale Interval 4.0 to 4.0	4.00 units on a scale Interval 3.0 to 4.0
Clinical Global Impression - Severity (CGI-S) Visit 3 - First Intervention	4.00 units on a scale Interval 3.0 to 4.0	4.00 units on a scale Interval 4.0 to 4.0
Clinical Global Impression - Severity (CGI-S) Visit 5 - First Intervention	4.00 units on a scale Interval 4.0 to 4.0	4.00 units on a scale Interval 4.0 to 5.0
Clinical Global Impression - Severity (CGI-S) Visit 6 - Second Intervention	4.00 units on a scale Interval 3.0 to 4.0	4.00 units on a scale Interval 4.0 to 5.0
Clinical Global Impression - Severity (CGI-S) Visit 8 - Second Intervention	4.00 units on a scale Interval 3.0 to 4.0	4.00 units on a scale Interval 4.0 to 5.0
Clinical Global Impression - Severity (CGI-S) Visit 10 - Second Intervention	4.00 units on a scale Interval 4.0 to 4.0	4.50 units on a scale Interval 4.0 to 5.0

PRIMARY outcome

Timeframe: Every 10 weeks during each of the two 20-week treatment periods

Population: Data was not collected at Visit 1 because participants had not yet been exposed to either intervention. One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

Each time the patient was seen after the study intervention was initiated, the clinician compared the patient's overall clinical condition to the CGI-S score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment. The possible range for reported scores is 1-7.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Clinical Global Impression - Improvement (CGI-I) Visit 3 - First Intervention	4.00 units on a scale Interval 4.0 to 4.0	4.00 units on a scale Interval 4.0 to 4.0
Clinical Global Impression - Improvement (CGI-I) Visit 5 - First Intervention	4.00 units on a scale Interval 4.0 to 4.0	4.00 units on a scale Interval 4.0 to 4.0
Clinical Global Impression - Improvement (CGI-I) Visit 6 - Second Intervention	4.00 units on a scale Interval 3.0 to 5.0	4.00 units on a scale Interval 4.0 to 5.0
Clinical Global Impression - Improvement (CGI-I) Visit 8 - Second Intervention	4.00 units on a scale Interval 4.0 to 4.0	4.00 units on a scale Interval 4.0 to 5.0
Clinical Global Impression - Improvement (CGI-I) Visit 10 - Second Intervention	4.00 units on a scale Interval 3.0 to 4.0	4.00 units on a scale Interval 3.0 to 5.0

PRIMARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Population: In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

The PGI-S is the parent version of the CGI-S. Parents/caregivers/LAR are asked to rate the severity of their child's symptoms at baseline on a 7-point scale from not at all impaired to the most impaired. The parents/caregivers/LAR will complete the PGI-S at each study visit. The scores that correspond to each possible grouping are as follows: 1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired. The possible range for reported scores is 1-7.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Parental Global Impression - Severity (PGI-S) Visit 1 - First Intervention	4.00 units on a scale Interval 3.0 to 4.0	6.00 units on a scale Interval 4.0 to 6.0
Parental Global Impression - Severity (PGI-S) Visit 2 - First Intervention	4.00 units on a scale Interval 3.0 to 6.0	4.00 units on a scale Interval 4.0 to 6.0
Parental Global Impression - Severity (PGI-S) Visit 3 - First Intervention	4.00 units on a scale Interval 3.0 to 4.0	4.00 units on a scale Interval 4.0 to 6.0
Parental Global Impression - Severity (PGI-S) Visit 4 - First Intervention	4.00 units on a scale Interval 4.0 to 4.0	4.00 units on a scale Interval 4.0 to 6.0
Parental Global Impression - Severity (PGI-S) Visit 5 - First Intervention	4.00 units on a scale Interval 4.0 to 6.0	4.00 units on a scale Interval 4.0 to 6.0
Parental Global Impression - Severity (PGI-S) Visit 6 - Second Intervention	4.00 units on a scale Interval 4.0 to 6.0	4.00 units on a scale Interval 4.0 to 6.0
Parental Global Impression - Severity (PGI-S) Visit 7 - Second Intervention	4.00 units on a scale Interval 3.0 to 4.0	4.00 units on a scale Interval 4.0 to 6.0
Parental Global Impression - Severity (PGI-S) Visit 8 - Second Intervention	4.00 units on a scale Interval 4.0 to 4.0	6.00 units on a scale Interval 4.0 to 6.0
Parental Global Impression - Severity (PGI-S) Visit 9 - Second Intervention	4.00 units on a scale Interval 4.0 to 4.0	6.00 units on a scale Interval 4.0 to 6.0
Parental Global Impression - Severity (PGI-S) Visit 10 - Second Intervention	4.00 units on a scale Interval 3.0 to 4.0	5.00 units on a scale Interval 4.0 to 6.0
Parental Global Impression - Severity (PGI-S) Follow-up	4.00 units on a scale Interval 3.0 to 4.0	4.00 units on a scale Interval 4.0 to 6.0

PRIMARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Population: Data was not collected at visit 1 because participants had not yet been exposed to either intervention. In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

As part of each visit after the study intervention was initiated, the parent/caregiver was asked to compare the patient's overall clinical condition to the score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment. The possible range for reported scores is 1-7.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Parental Global Impression - Improvement (PGI-I) Follow-up	3.00 units on a scale Interval 2.0 to 3.0	3.00 units on a scale Interval 3.0 to 3.0
Parental Global Impression - Improvement (PGI-I) Visit 2 - First Intervention	4.00 units on a scale Interval 3.0 to 4.0	4.00 units on a scale Interval 4.0 to 4.0
Parental Global Impression - Improvement (PGI-I) Visit 3 - First Intervention	3.00 units on a scale Interval 3.0 to 4.0	4.00 units on a scale Interval 3.0 to 4.0
Parental Global Impression - Improvement (PGI-I) Visit 4 - First Intervention	3.00 units on a scale Interval 3.0 to 4.0	4.00 units on a scale Interval 3.0 to 4.0
Parental Global Impression - Improvement (PGI-I) Visit 5 - First Intervention	3.00 units on a scale Interval 3.0 to 4.0	3.00 units on a scale Interval 3.0 to 4.0
Parental Global Impression - Improvement (PGI-I) Visit 6 - Second Intervention	4.00 units on a scale Interval 2.0 to 4.0	3.00 units on a scale Interval 3.0 to 4.0
Parental Global Impression - Improvement (PGI-I) Visit 7 - Second Intervention	3.00 units on a scale Interval 3.0 to 4.0	3.00 units on a scale Interval 3.0 to 3.0
Parental Global Impression - Improvement (PGI-I) Visit 8 - Second Intervention	3.00 units on a scale Interval 3.0 to 4.0	3.00 units on a scale Interval 3.0 to 3.0
Parental Global Impression - Improvement (PGI-I) Visit 9 - Second Intervention	3.00 units on a scale Interval 3.0 to 5.0	3.00 units on a scale Interval 3.0 to 3.0
Parental Global Impression - Improvement (PGI-I) Visit 10 - Second Intervention	3.00 units on a scale Interval 3.0 to 3.0	3.00 units on a scale Interval 3.0 to 3.0

PRIMARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Population: In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS). The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Visit 1 - First Intervention	6.50 units on a scale Interval 3.25 to 8.4	8.80 units on a scale Interval 5.05 to 9.85
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Visit 2 - First Intervention	4.70 units on a scale Interval 3.45 to 7.7	4.80 units on a scale Interval 2.3 to 8.95
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Visit 3 - First Intervention	5.65 units on a scale Interval 3.55 to 8.9	5.35 units on a scale Interval 3.8 to 9.35
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Visit 4 - First Intervention	5.05 units on a scale Interval 2.55 to 7.7	5.10 units on a scale Interval 4.8 to 9.1
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Visit 5 - First Intervention	4.80 units on a scale Interval 2.0 to 7.5	5.15 units on a scale Interval 2.9 to 9.55
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Visit 6 - Second Intervention	4.95 units on a scale Interval 3.75 to 8.5	5.20 units on a scale Interval 4.7 to 9.25
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Visit 7 - Second Intervention	4.55 units on a scale Interval 2.55 to 6.0	4.65 units on a scale Interval 3.85 to 7.25
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Visit 8 - Second Intervention	5.65 units on a scale Interval 3.7 to 7.55	5.00 units on a scale Interval 3.65 to 7.45
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Visit 9 - Second Intervention	4.15 units on a scale Interval 2.45 to 6.45	5.15 units on a scale Interval 3.63 to 8.58
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Visit 10 - Second Intervention	4.80 units on a scale Interval 2.5 to 6.9	5.05 units on a scale Interval 4.2 to 8.5
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1 Follow-up	5.60 units on a scale Interval 1.4 to 6.25	5.08 units on a scale Interval 4.13 to 8.13

PRIMARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Population: In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Visit 1 - First Intervention	7.75 units on a scale Interval 4.8 to 9.45	6.35 units on a scale Interval 5.2 to 9.85
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Visit 2 - First Intervention	4.50 units on a scale Interval 3.75 to 5.0	5.25 units on a scale Interval 4.85 to 8.4
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Visit 3 - First Intervention	5.85 units on a scale Interval 4.3 to 7.25	5.95 units on a scale Interval 4.95 to 8.9
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Visit 4 - First Intervention	5.00 units on a scale Interval 3.05 to 6.2	5.40 units on a scale Interval 4.9 to 6.45
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Visit 5 - First Intervention	5.00 units on a scale Interval 3.3 to 6.1	5.45 units on a scale Interval 1.4 to 7.8
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Visit 6 - Second Intervention	5.35 units on a scale Interval 4.95 to 7.85	7.10 units on a scale Interval 4.95 to 9.25
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Visit 7 - Second Intervention	5.50 units on a scale Interval 3.85 to 6.2	5.85 units on a scale Interval 3.4 to 6.9
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Visit 8 - Second Intervention	5.15 units on a scale Interval 3.8 to 7.2	5.00 units on a scale Interval 3.0 to 7.6
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Visit 9 - Second Intervention	3.80 units on a scale Interval 1.7 to 6.35	5.13 units on a scale Interval 3.43 to 7.05
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Visit 10 - Second Intervention	4.90 units on a scale Interval 2.6 to 6.8	4.95 units on a scale Interval 2.25 to 8.15
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2 Follow-up	5.15 units on a scale Interval 3.85 to 6.65	5.20 units on a scale Interval 3.6 to 7.95

PRIMARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Population: In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Visit 1 - First Intervention	7.85 units on a scale Interval 5.7 to 8.7	5.70 units on a scale Interval 4.5 to 9.65
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Visit 2 - First Intervention	4.70 units on a scale Interval 4.48 to 8.3	5.00 units on a scale Interval 2.55 to 5.4
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Visit 3 - First Intervention	5.65 units on a scale Interval 3.65 to 9.0	5.20 units on a scale Interval 3.5 to 9.4
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Visit 4 - First Intervention	4.15 units on a scale Interval 2.9 to 6.05	5.35 units on a scale Interval 3.5 to 8.65
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Visit 5 - First Intervention	5.00 units on a scale Interval 4.4 to 7.4	5.10 units on a scale Interval 4.0 to 8.2
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Visit 6 - Second Intervention	6.20 units on a scale Interval 4.7 to 8.35	5.35 units on a scale Interval 4.05 to 9.05
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Visit 7 - Second Intervention	4.80 units on a scale Interval 3.15 to 7.3	4.95 units on a scale Interval 2.95 to 7.05
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Visit 8 - Second Intervention	4.85 units on a scale Interval 3.8 to 8.15	5.15 units on a scale Interval 1.75 to 7.1
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Visit 9 - Second Intervention	4.60 units on a scale Interval 3.15 to 7.9	5.25 units on a scale Interval 3.35 to 7.1
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Visit 10 - Second Intervention	4.13 units on a scale Interval 1.1 to 8.45	4.55 units on a scale Interval 2.95 to 5.45
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3 Follow-up	4.55 units on a scale Interval 2.2 to 7.0	5.10 units on a scale Interval 3.2 to 8.03

PRIMARY outcome

Timeframe: At the start and end of each 20-week treatment period

Population: In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms. One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

The Kerr clinical severity scale (Kerr scale) is a quantitative measure of global disease severity. The Kerr scale is a summation of individual items related to Rett syndrome phenotypic characteristics. The items are based on the severity or degree of abnormality of each characteristic on a discrete scale (0, 1, 2) with the highest level corresponding to the most severe or most abnormal presentations. The possible range of scores is 0-48. The higher the score, the more severe the symptoms.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Kerr Clinical Severity Scale Visit 10 - Second Intervention	14.00 units on a scale Interval 13.0 to 22.0	20.00 units on a scale Interval 17.0 to 22.0
Kerr Clinical Severity Scale Visit 1 - First Intervention	16.50 units on a scale Interval 13.0 to 20.0	18.00 units on a scale Interval 12.0 to 22.0
Kerr Clinical Severity Scale Visit 5 - First Intervention	15.00 units on a scale Interval 13.0 to 21.0	18.00 units on a scale Interval 14.0 to 22.0
Kerr Clinical Severity Scale Visit 6 - Second Intervention	15.00 units on a scale Interval 12.0 to 20.0	19.00 units on a scale Interval 16.0 to 22.0

SECONDARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

The RSBQ is a parent-completed measure of abnormal behaviors typically observed in individuals with RTT. Each item, grouped into eight subscales, is scored on a Likert scale of 0-2, according to how well the item describes the individual's behavior. A score of "0" indicates the described item is "not true," a score of "1" indicates the described item is "somewhat or sometimes true," and a score of "2" indicates the described item is "very true or often true." The total sum of each subscale is reported. The higher the score, the more severe the symptoms of that subscale in the participant. The range for each subscale is as follows: General Mood: 0-16 Body rocking and expressionless face: 0-14 Hand behaviors: 0-12 Breathing Problems: 0-10 Repetitive Face Movements: 0-8 Night-time behaviors: 0-6 Walking Standing: 0-4 The fear/anxiety subscale was used as a primary outcome measure in this study and results can be found in that section.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 1- First Intervention: General Mood	7.00 units on a scale Interval 4.0 to 11.0	4.00 units on a scale Interval 3.0 to 7.0
Rett Syndrome Behavior Questionnaire (RSBQ) Follow-up: Walking/Standing	2.00 units on a scale Interval 1.0 to 3.0	2.00 units on a scale Interval 2.0 to 3.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 2- First Intervention: General Mood	5.00 units on a scale Interval 3.0 to 8.0	3.00 units on a scale Interval 1.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 3- First Intervention: General Mood	6.00 units on a scale Interval 1.0 to 8.0	2.00 units on a scale Interval 1.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 4- First Intervention: General Mood	5.00 units on a scale Interval 3.0 to 8.0	2.00 units on a scale Interval 1.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 5- First Intervention: General Mood	5.00 units on a scale Interval 1.0 to 8.0	3.00 units on a scale Interval 1.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 6- Second Intervention: General Mood	4.00 units on a scale Interval 2.0 to 8.0	4.00 units on a scale Interval 2.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 7- Second Intervention: General Mood	5.50 units on a scale Interval 2.0 to 7.0	2.00 units on a scale Interval 1.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 8- Second Intervention: General Mood	5.00 units on a scale Interval 2.0 to 8.0	2.00 units on a scale Interval 1.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 9- Second Intervention: General Mood	6.00 units on a scale Interval 3.0 to 8.0	1.00 units on a scale Interval 1.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 10- Second Intervention: General Mood	4.00 units on a scale Interval 2.0 to 8.0	2.50 units on a scale Interval 1.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) Follow-up: General Mood	5.50 units on a scale Interval 3.0 to 6.0	2.00 units on a scale Interval 1.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 1- First Intervention: Body Rocking	6.00 units on a scale Interval 5.0 to 10.0	4.00 units on a scale Interval 4.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 2- First Intervention: Body Rocking	5.00 units on a scale Interval 4.0 to 7.0	4.00 units on a scale Interval 3.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 3- First Intervention: Body Rocking	5.00 units on a scale Interval 3.0 to 8.0	3.00 units on a scale Interval 2.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 4- First Intervention: Body Rocking	6.00 units on a scale Interval 4.0 to 7.0	4.00 units on a scale Interval 2.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 5- First Intervention: Body Rocking	5.00 units on a scale Interval 3.0 to 8.0	4.00 units on a scale Interval 2.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 6- Second Intervention: Body Rocking	4.00 units on a scale Interval 3.0 to 7.0	4.00 units on a scale Interval 3.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 7- Second Intervention: Body Rocking	5.00 units on a scale Interval 3.0 to 7.0	3.00 units on a scale Interval 3.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 8- Second Intervention: Body Rocking	5.00 units on a scale Interval 3.0 to 6.0	4.00 units on a scale Interval 2.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 9- Second Intervention: Body Rocking	4.00 units on a scale Interval 3.0 to 7.0	3.00 units on a scale Interval 2.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 10- Second Intervention: Body Rocking	5.00 units on a scale Interval 3.0 to 7.0	4.00 units on a scale Interval 2.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Followup: Body Rocking	4.50 units on a scale Interval 3.0 to 7.0	4.00 units on a scale Interval 2.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 1- First Intervention: Hand Behaviors	8.00 units on a scale Interval 7.0 to 10.0	8.00 units on a scale Interval 5.0 to 10.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 2- First Intervention: Hand Behaviors	9.00 units on a scale Interval 6.0 to 9.0	8.00 units on a scale Interval 6.0 to 10.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 3- First Intervention: Hand Behaviors	8.00 units on a scale Interval 7.0 to 10.0	8.00 units on a scale Interval 5.0 to 9.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 4- First Intervention: Hand Behaviors	8.00 units on a scale Interval 6.0 to 9.0	9.00 units on a scale Interval 6.0 to 9.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 5- First Intervention: Hand Behaviors	8.00 units on a scale Interval 6.0 to 10.0	9.00 units on a scale Interval 5.0 to 10.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 6- Second Intervention: Hand Behaviors	9.00 units on a scale Interval 6.0 to 10.0	8.00 units on a scale Interval 7.0 to 10.0
Rett Syndrome Behavior Questionnaire (RSBQ) Follow-up: Night time Behaviors	0.00 units on a scale Interval 0.0 to 1.0	0.00 units on a scale Interval 0.0 to 1.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 7- Second Intervention: Hand Behaviors	8.00 units on a scale Interval 5.0 to 10.0	9.00 units on a scale Interval 6.0 to 9.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 8- Second Intervention: Hand Behaviors	8.00 units on a scale Interval 6.0 to 9.0	9.00 units on a scale Interval 6.0 to 9.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 9- Second Intervention: Hand Behaviors	8.00 units on a scale Interval 5.0 to 9.0	7.00 units on a scale Interval 6.0 to 10.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 10- Second Intervention: Hand Behaviors	7.00 units on a scale Interval 6.0 to 9.0	9.00 units on a scale Interval 6.0 to 10.0
Rett Syndrome Behavior Questionnaire (RSBQ) Follow-up: Hand Behaviors	7.50 units on a scale Interval 7.0 to 9.0	8.50 units on a scale Interval 6.0 to 10.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 1- First Intervention: Breathing Problems	6.00 units on a scale Interval 3.0 to 9.0	4.00 units on a scale Interval 3.0 to 7.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 2- First Intervention: Breathing Problems	4.00 units on a scale Interval 2.0 to 8.0	4.00 units on a scale Interval 2.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 3- First Intervention: Breathing Problems	5.00 units on a scale Interval 2.0 to 8.0	4.00 units on a scale Interval 2.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 4- First Intervention: Breathing Problems	5.00 units on a scale Interval 3.0 to 7.0	5.00 units on a scale Interval 2.0 to 7.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 5- First Intervention: Breathing Problems	5.00 units on a scale Interval 1.0 to 8.0	4.00 units on a scale Interval 2.0 to 7.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 6- Second Intervention: Breathing Problems	6.00 units on a scale Interval 2.0 to 9.0	4.00 units on a scale Interval 1.0 to 8.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 7- Second Intervention: Breathing Problems	4.50 units on a scale Interval 2.0 to 7.0	3.00 units on a scale Interval 1.0 to 7.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 8- Second Intervention: Breathing Problems	6.00 units on a scale Interval 3.0 to 7.0	3.00 units on a scale Interval 1.0 to 6.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 9- Second Intervention: Breathing Problems	5.00 units on a scale Interval 2.0 to 7.0	3.00 units on a scale Interval 0.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 10- Second Intervention: Breathing Problems	6.00 units on a scale Interval 3.0 to 7.0	4.00 units on a scale Interval 1.0 to 5.0
Rett Syndrome Behavior Questionnaire (RSBQ) Follow-up: Breathing Problems	5.00 units on a scale Interval 2.0 to 7.0	3.00 units on a scale Interval 0.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 1- First Intervention: Repetitive Face Movem	2.00 units on a scale Interval 1.0 to 5.0	2.00 units on a scale Interval 2.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 2- First Intervention: Repetitive Face Movem	2.00 units on a scale Interval 0.0 to 4.0	2.00 units on a scale Interval 2.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 3- First Intervention: Repetitive Face Movem	3.00 units on a scale Interval 1.0 to 4.0	3.00 units on a scale Interval 2.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 4- First Intervention: Repetitive Face Movem	2.00 units on a scale Interval 1.0 to 5.0	2.00 units on a scale Interval 1.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 5- First Intervention: Repetitive Face Movem	3.00 units on a scale Interval 0.0 to 5.0	2.00 units on a scale Interval 0.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 6- Second Intervention: Repetitive Face Mov	3.00 units on a scale Interval 2.0 to 5.0	3.00 units on a scale Interval 2.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 7- Second Intervention: Repetitive Face Mov	3.00 units on a scale Interval 1.0 to 5.0	2.00 units on a scale Interval 0.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 8- Second Intervention: Repetitive Face Mov	3.00 units on a scale Interval 2.0 to 4.0	2.00 units on a scale Interval 1.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 9- Second Intervention: Repetitive Face Mov	3.00 units on a scale Interval 1.0 to 5.0	2.00 units on a scale Interval 0.0 to 3.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 10- Second Intervention: Repetitive Face Mov	3.00 units on a scale Interval 1.0 to 5.0	1.50 units on a scale Interval 1.0 to 4.0
Rett Syndrome Behavior Questionnaire (RSBQ) Follow-up: Repetitive Face Movements	2.00 units on a scale Interval 1.0 to 4.0	2.00 units on a scale Interval 0.0 to 2.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 1- First Intervention: Night time Behaviors	0.00 units on a scale Interval 0.0 to 2.0	1.00 units on a scale Interval 0.0 to 2.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 2- First Intervention: Night time Behaviors	0.00 units on a scale Interval 0.0 to 3.0	1.00 units on a scale Interval 0.0 to 2.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 3- First Intervention: Night time Behaviors	0.00 units on a scale Interval 0.0 to 0.0	0.00 units on a scale Interval 0.0 to 2.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 4- First Intervention: Night time Behaviors	0.00 units on a scale Interval 0.0 to 2.0	0.00 units on a scale Interval 0.0 to 1.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 5- First Intervention: Night time Behaviors	0.00 units on a scale Interval 0.0 to 2.0	1.00 units on a scale Interval 0.0 to 2.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 6- Second Intervention: Night time Behavior	0.00 units on a scale Interval 0.0 to 2.0	1.00 units on a scale Interval 0.0 to 2.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 7- Second Intervention: Night time Behavior	0.00 units on a scale Interval 0.0 to 2.0	0.00 units on a scale Interval 0.0 to 1.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 8- Second Intervention: Night time Behavior	1.00 units on a scale Interval 0.0 to 2.0	0.00 units on a scale Interval 0.0 to 1.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 9- Second Intervention: Night time Behavior	0.00 units on a scale Interval 0.0 to 3.0	0.00 units on a scale Interval 0.0 to 1.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 10- Second Intervention: Night time Behavior	0.00 units on a scale Interval 0.0 to 1.0	0.00 units on a scale Interval 0.0 to 1.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 1- First Intervention: Walking/Standing	2.00 units on a scale Interval 2.0 to 3.0	2.00 units on a scale Interval 1.0 to 3.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 2- First Intervention: Walking/Standing	2.00 units on a scale Interval 1.0 to 3.0	2.00 units on a scale Interval 1.0 to 3.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 3- First Intervention: Walking/Standing	2.00 units on a scale Interval 2.0 to 2.0	2.00 units on a scale Interval 1.0 to 3.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 4- First Intervention: Walking/Standing	2.00 units on a scale Interval 1.0 to 3.0	2.00 units on a scale Interval 1.0 to 3.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 5- First Intervention: Walking/Standing	2.00 units on a scale Interval 1.0 to 3.0	2.00 units on a scale Interval 1.0 to 3.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 6- Second Intervention: Walking/Standing	2.00 units on a scale Interval 2.0 to 3.0	2.00 units on a scale Interval 1.0 to 2.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 7- Second Intervention: Walking/Standing	2.00 units on a scale Interval 2.0 to 3.0	2.00 units on a scale Interval 1.0 to 3.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 8- Second Intervention: Walking/Standing	2.00 units on a scale Interval 1.0 to 3.0	2.00 units on a scale Interval 1.0 to 3.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 9- Second Intervention: Walking/Standing	3.00 units on a scale Interval 1.0 to 3.0	2.00 units on a scale Interval 1.0 to 2.0
Rett Syndrome Behavior Questionnaire (RSBQ) Visit 10- Second Intervention: Walking/Standing	1.50 units on a scale Interval 1.0 to 3.0	2.00 units on a scale Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Remaining subscales of the ADAMS that are not primary outcome measures include: Manic/hyperactive, Depressed mood, General anxiety, Obsessive/compulsive behavior. The range for each subscale is as follows: Manic/Hyperactive Behavior: 0-15 Depressed Mood: 0-21 General Anxiety: 0-21 Obsessive/Compulsive Behavior: 0-9 The higher the score for each subscale, the more problematic the behavior.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Anxiety, Depression, and Mood Scale (ADAMS) Follow-up: Obsessive Compulsive Behavior Subscale	3.50 units on a scale Interval 2.0 to 4.0	3.00 units on a scale Interval 0.0 to 4.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 1- First Intervention: Manic/Hyperactive	8.00 units on a scale Interval 5.0 to 11.0	7.00 units on a scale Interval 5.0 to 9.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 2- First Intervention: Manic/Hyperactive	7.00 units on a scale Interval 3.0 to 10.0	7.00 units on a scale Interval 4.0 to 9.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 3- First Intervention: Manic/Hyperactive	7.00 units on a scale Interval 3.0 to 9.0	6.00 units on a scale Interval 4.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 4- First Intervention: Manic/Hyperactive	7.00 units on a scale Interval 5.0 to 9.0	5.00 units on a scale Interval 4.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 5- First Intervention: Manic/Hyperactive	7.00 units on a scale Interval 4.0 to 9.0	4.00 units on a scale Interval 3.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 6- Second Intervention: Manic/Hyperactive	8.00 units on a scale Interval 3.0 to 9.0	6.00 units on a scale Interval 5.0 to 8.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 7- Second Intervention: Manic/Hyperactive	6.50 units on a scale Interval 3.0 to 9.0	5.00 units on a scale Interval 3.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 8- Second Intervention: Manic/Hyperactive	6.00 units on a scale Interval 3.0 to 8.0	5.00 units on a scale Interval 3.0 to 6.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 9- Second Intervention: Manic/Hyperactive	6.00 units on a scale Interval 4.0 to 9.0	4.00 units on a scale Interval 1.0 to 6.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 10- First Intervention: Manic/Hyperactive	5.00 units on a scale Interval 2.0 to 7.0	4.50 units on a scale Interval 2.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) Follow-up: Manic/Hyperactive Subscale	5.00 units on a scale Interval 3.0 to 9.0	5.00 units on a scale Interval 3.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 1- First Intervention: Depressed Mood	2.00 units on a scale Interval 2.0 to 7.0	4.00 units on a scale Interval 3.0 to 6.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 2- First Intervention: Depressed Mood	4.00 units on a scale Interval 1.0 to 5.0	5.00 units on a scale Interval 2.0 to 6.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 3- First Intervention: Depressed Mood	3.00 units on a scale Interval 1.0 to 5.0	3.00 units on a scale Interval 2.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 4- First Intervention: Depressed Mood	2.00 units on a scale Interval 1.0 to 4.0	3.00 units on a scale Interval 1.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 5- First Intervention: Depressed Mood	2.00 units on a scale Interval 1.0 to 4.0	4.00 units on a scale Interval 0.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 6- Second Intervention: Depressed Mood	2.00 units on a scale Interval 0.0 to 5.0	4.00 units on a scale Interval 3.0 to 6.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 7- Second Intervention: Depressed Mood	3.00 units on a scale Interval 0.0 to 6.0	3.00 units on a scale Interval 2.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 8- Second Intervention: Depressed Mood	2.00 units on a scale Interval 1.0 to 5.0	3.00 units on a scale Interval 1.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 9- Second Intervention: Depressed Mood	3.00 units on a scale Interval 0.0 to 4.0	2.00 units on a scale Interval 1.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 10- Second Intervention: Depressed Mood	2.00 units on a scale Interval 1.0 to 4.0	3.00 units on a scale Interval 2.0 to 4.0
Anxiety, Depression, and Mood Scale (ADAMS) Follow-up: Depressed Mood Subscale	2.00 units on a scale Interval 0.0 to 5.0	3.50 units on a scale Interval 0.0 to 4.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 1- First Intervention: General Anxiety	8.00 units on a scale Interval 5.0 to 12.0	6.00 units on a scale Interval 5.0 to 12.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 2- First Intervention: General Anxiety	6.00 units on a scale Interval 4.0 to 12.0	7.00 units on a scale Interval 3.0 to 10.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 3- First Intervention: General Anxiety	6.00 units on a scale Interval 3.0 to 9.0	6.00 units on a scale Interval 3.0 to 9.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 4- First Intervention: General Anxiety	5.00 units on a scale Interval 2.0 to 11.0	5.00 units on a scale Interval 2.0 to 8.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 5- First Intervention: General Anxiety	5.00 units on a scale Interval 2.0 to 10.0	5.00 units on a scale Interval 3.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 6- Second Intervention: General Anxiety	6.00 units on a scale Interval 3.0 to 9.0	7.00 units on a scale Interval 3.0 to 11.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 7- Second Intervention: General Anxiety	6.00 units on a scale Interval 2.0 to 8.0	5.00 units on a scale Interval 1.0 to 7.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 8- Second Intervention: General Anxiety	6.00 units on a scale Interval 3.0 to 9.0	4.00 units on a scale Interval 2.0 to 8.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 9- Second Intervention: General Anxiety	4.00 units on a scale Interval 2.0 to 8.0	3.00 units on a scale Interval 1.0 to 6.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 10- Second Intervention: General Anxiety	4.00 units on a scale Interval 2.0 to 7.0	4.00 units on a scale Interval 2.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) Follow-up: General Anxiety Subscale	5.50 units on a scale Interval 3.0 to 9.0	4.00 units on a scale Interval 1.0 to 6.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 1- First Intervention: Obsessive Compulsive	4.00 units on a scale Interval 3.0 to 6.0	3.00 units on a scale Interval 0.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 2- First Intervention: Obsessive Compulsive	4.00 units on a scale Interval 2.0 to 4.0	4.00 units on a scale Interval 1.0 to 4.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 3- First Intervention: Obsessive Compulsive	4.00 units on a scale Interval 1.0 to 4.0	4.00 units on a scale Interval 1.0 to 4.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 4- First Intervention: Obsessive Compulsive	3.00 units on a scale Interval 3.0 to 4.0	3.00 units on a scale Interval 1.0 to 4.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 5- First Intervention: Obsessive Compulsive	3.00 units on a scale Interval 2.0 to 4.0	3.00 units on a scale Interval 0.0 to 4.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 6- Second Intervention: Obsessive Compulsive	3.00 units on a scale Interval 1.0 to 5.0	3.00 units on a scale Interval 1.0 to 5.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 7- Second Intervention: Obsessive Compulsive	3.00 units on a scale Interval 2.0 to 6.0	3.00 units on a scale Interval 0.0 to 4.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 8- Second Intervention: Obsessive Compulsive	3.00 units on a scale Interval 2.0 to 4.0	3.00 units on a scale Interval 0.0 to 4.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 9- Second Intervention: Obsessive Compulsive	3.00 units on a scale Interval 1.0 to 3.0	2.00 units on a scale Interval 0.0 to 4.0
Anxiety, Depression, and Mood Scale (ADAMS) Visit 10- First Intervention: Obsessive Compulsive	2.00 units on a scale Interval 1.0 to 4.0	2.50 units on a scale Interval 0.0 to 5.0

SECONDARY outcome

Timeframe: At the start and end of each 20-week treatment period

Population: One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point. In some cases, the number of participants analyzed is less than 15 for each group due to subject's inability or unwillingness to complete the testing.

The MSEL is a standardized developmental test for children ages 3 to 68 months consisting of five subscales: gross motor, fine motor, visual reception, expressive language, and receptive language. The raw score is reported for each subscale domain. The potential score ranges are as follows: Visual Reception: 33 items, score range=0-50, Fine Motor: 30 items, score range= 0-49, Receptive Language: 33 items, score range= 0-48, Expressive Language: 28 items, score range= 0-50. The gross motor subscale was not included in this population. A higher raw score indicates more advanced abilities in that section.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Mullen Scales of Early Learning (MSEL) Visit 6- Second Intervention: Receptive Language	31.00 units on a scale Interval 24.0 to 35.0	38.00 units on a scale Interval 33.0 to 47.0
Mullen Scales of Early Learning (MSEL) Visit 10- Second Intervention: Receptive Language	31.00 units on a scale Interval 26.0 to 38.0	36.50 units on a scale Interval 27.0 to 44.0
Mullen Scales of Early Learning (MSEL) Visit 1- First Intervention: Expressive Language	8.00 units on a scale Interval 5.0 to 9.0	9.00 units on a scale Interval 6.0 to 11.0
Mullen Scales of Early Learning (MSEL) Visit 5- First Intervention: Expressive Language	9.00 units on a scale Interval 5.0 to 11.0	8.00 units on a scale Interval 5.0 to 11.0
Mullen Scales of Early Learning (MSEL) Visit 1- First Intervention: Visual Reception	17.00 units on a scale Interval 15.0 to 25.0	26.00 units on a scale Interval 18.0 to 42.0
Mullen Scales of Early Learning (MSEL) Visit 5- First Intervention: Visual Reception	26.00 units on a scale Interval 16.0 to 33.0	39.50 units on a scale Interval 20.0 to 49.0
Mullen Scales of Early Learning (MSEL) Visit 6- Second Intervention: Visual Reception	23.00 units on a scale Interval 20.0 to 36.0	42.00 units on a scale Interval 23.0 to 48.0
Mullen Scales of Early Learning (MSEL) Visit 10: Visual Reception Raw Score	28.00 units on a scale Interval 25.0 to 41.0	44.00 units on a scale Interval 28.0 to 48.0
Mullen Scales of Early Learning (MSEL) Visit 1- First Intervention: Fine Motor	10.00 units on a scale Interval 7.0 to 14.0	7.00 units on a scale Interval 6.0 to 17.0
Mullen Scales of Early Learning (MSEL) Visit 5- First Intervention: Fine Motor	9.00 units on a scale Interval 6.0 to 13.0	7.00 units on a scale Interval 3.0 to 15.0
Mullen Scales of Early Learning (MSEL) Visit 6- Second Intervention: Fine Motor	11.00 units on a scale Interval 7.0 to 13.0	10.00 units on a scale Interval 5.0 to 17.0
Mullen Scales of Early Learning (MSEL) Visit 10- Second Intervention: Fine Motor	9.00 units on a scale Interval 6.0 to 13.0	8.50 units on a scale Interval 4.0 to 13.0
Mullen Scales of Early Learning (MSEL) Visit 1- First Intervention: Receptive Language	20.00 units on a scale Interval 17.0 to 31.0	25.50 units on a scale Interval 17.0 to 40.0
Mullen Scales of Early Learning (MSEL) Visit 5- First Intervention: Receptive Language	30.00 units on a scale Interval 19.0 to 33.0	32.00 units on a scale Interval 25.0 to 44.0
Mullen Scales of Early Learning (MSEL) Visit 6- Second Intervention: Expressive Language	6.00 units on a scale Interval 5.0 to 9.0	10.00 units on a scale Interval 5.0 to 12.0
Mullen Scales of Early Learning (MSEL) Visit 10- Second Intervention: Expressive Language	8.00 units on a scale Interval 5.0 to 10.0	8.00 units on a scale Interval 6.0 to 12.0

SECONDARY outcome

Timeframe: At the start and end of each 20-week treatment period

Population: One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

The VABS-II is a survey designed to assess personal and social functioning. Within each domain (Communication, Daily Living Skills, Socialization, and Motor Skills), items can given a score of "2" if the participant successfully performs the activity usually; a "1" if the participant successfully performs the activity sometimes, or needs reminders; a "0" if the participant never performs the activity, and a "DK" if the parent/caregiver is unsure of the participant's ability for an item. The raw scores in each sub-domain are reported and the ranges for these are as follows: \[Communication Domain\], Receptive Language=0-40, Expressive Language=0-108, Written Language=0-50; \[Daily Living Skills Domain\], Personal=0-82, Domestic=0-48, Community=0-88; \[Socialization Domain\], Interpersonal Relationships=0-76, Play and Leisure Time=0-62, Coping Skills=0-60; \[Motor Skills Domain\]: Gross Motor Skills=0-80, Fine Motor Skills=0-72. A higher score indicates more advanced abilities.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Receptive	13.00 units on a scale Interval 9.0 to 16.0	18.00 units on a scale Interval 13.0 to 20.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Receptive	15.00 units on a scale Interval 14.0 to 20.0	21.00 units on a scale Interval 17.0 to 23.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6 - Second Intervention: Receptive Language	18.00 units on a scale Interval 13.0 to 20.0	22.00 units on a scale Interval 20.0 to 24.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Receptive Language	20.00 units on a scale Interval 15.0 to 24.0	24.50 units on a scale Interval 20.0 to 29.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Expressive	16.00 units on a scale Interval 12.0 to 17.0	18.00 units on a scale Interval 13.0 to 25.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Expressive	17.00 units on a scale Interval 13.0 to 23.0	22.00 units on a scale Interval 18.0 to 29.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6 - Second Intervention: Expressive Lang.	18.00 units on a scale Interval 11.0 to 23.0	25.00 units on a scale Interval 18.0 to 31.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Expressive Lang.	20.00 units on a scale Interval 15.0 to 28.0	24.00 units on a scale Interval 23.0 to 34.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Written	0.00 units on a scale Interval 0.0 to 1.0	4.00 units on a scale Interval 0.0 to 7.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Written	0.00 units on a scale Interval 0.0 to 5.0	5.00 units on a scale Interval 0.0 to 9.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6: - Second Intervention Written Language	4.00 units on a scale Interval 1.0 to 7.0	7.00 units on a scale Interval 2.0 to 9.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Written Language	6.00 units on a scale Interval 0.0 to 8.0	7.00 units on a scale Interval 4.0 to 10.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Personal	9.00 units on a scale Interval 7.0 to 10.0	8.00 units on a scale Interval 6.0 to 10.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Personal	10.00 units on a scale Interval 8.0 to 13.0	9.00 units on a scale Interval 7.0 to 13.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6 - Second Intervention: Personal	9.00 units on a scale Interval 8.0 to 14.0	8.50 units on a scale Interval 8.0 to 16.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Personal	10.00 units on a scale Interval 7.0 to 14.0	9.50 units on a scale Interval 8.0 to 10.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Domestic	0.00 units on a scale Interval 0.0 to 0.0	0.00 units on a scale Interval 0.0 to 1.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Domestic	0.00 units on a scale Interval 0.0 to 0.0	0.00 units on a scale Interval 0.0 to 1.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6 - Second Intervention: Domestic	0.00 units on a scale Interval 0.0 to 0.0	0.00 units on a scale Interval 0.0 to 2.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Domestic	0.00 units on a scale Interval 0.0 to 1.0	0.00 units on a scale Interval 0.0 to 1.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Community	0.00 units on a scale Interval 0.0 to 1.0	3.00 units on a scale Interval 2.0 to 6.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Community	1.00 units on a scale Interval 0.0 to 2.0	3.00 units on a scale Interval 2.0 to 4.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6 - Second Intervention: Community	1.00 units on a scale Interval 0.0 to 3.0	5.00 units on a scale Interval 2.0 to 7.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Community	2.00 units on a scale Interval 0.0 to 5.0	5.00 units on a scale Interval 2.0 to 7.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Interpersonal Rel.	18.00 units on a scale Interval 15.0 to 21.0	21.00 units on a scale Interval 17.0 to 24.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Interpersonal Rel.	18.00 units on a scale Interval 15.0 to 21.0	22.00 units on a scale Interval 17.0 to 25.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6 - Second Intervention: Interpersonal Rel.	19.00 units on a scale Interval 15.0 to 21.0	21.00 units on a scale Interval 20.0 to 26.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Interpersonal Rel.	20.00 units on a scale Interval 16.0 to 23.0	22.50 units on a scale Interval 19.0 to 27.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Play and Leisure	8.00 units on a scale Interval 7.0 to 12.0	13.00 units on a scale Interval 11.0 to 17.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Play and Leisure	11.00 units on a scale Interval 9.0 to 12.0	12.00 units on a scale Interval 11.0 to 16.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6 - Second Intervention: Play and Leisure	12.00 units on a scale Interval 9.0 to 14.0	13.00 units on a scale Interval 11.0 to 16.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Play and Leisure	11.00 units on a scale Interval 9.0 to 15.0	12.50 units on a scale Interval 10.0 to 16.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Coping Skills	3.00 units on a scale Interval 2.0 to 4.0	3.00 units on a scale Interval 3.0 to 4.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Coping Skills	2.00 units on a scale Interval 2.0 to 4.0	4.00 units on a scale Interval 2.0 to 6.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6 - Second Intervention: Coping Skills	3.00 units on a scale Interval 3.0 to 4.0	6.00 units on a scale Interval 3.0 to 6.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Coping Skills	4.00 units on a scale Interval 3.0 to 5.0	4.50 units on a scale Interval 3.0 to 8.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Gross Motor	31.00 units on a scale Interval 21.0 to 37.0	10.00 units on a scale Interval 7.0 to 43.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Gross Motor	34.00 units on a scale Interval 22.0 to 42.0	10.00 units on a scale Interval 8.0 to 36.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6 - Second Intervention: Gross Motor	27.00 units on a scale Interval 12.0 to 45.0	11.50 units on a scale Interval 8.0 to 34.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Gross Motor	27.00 units on a scale Interval 14.0 to 46.0	10.50 units on a scale Interval 8.0 to 30.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 1 - First Intervention: Fine Motor	6.00 units on a scale Interval 3.0 to 8.0	2.00 units on a scale Interval 1.0 to 14.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 5 - First Intervention: Fine Motor	6.00 units on a scale Interval 4.0 to 9.0	3.00 units on a scale Interval 2.0 to 15.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 6 - Second Intervention: Fine Motor	7.00 units on a scale Interval 3.0 to 10.0	4.00 units on a scale Interval 2.0 to 16.0
Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Visit 10 - Second Intervention: Fine Motor	5.00 units on a scale Interval 2.0 to 9.0	4.00 units on a scale Interval 2.0 to 8.0

SECONDARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

The CSBS-DP was designed to measure early communication and symbolic skills in infants and young children (that is, functional communication skills of 6 month to 2 year olds). The CSBS-DP measures skills from three composites: (a) Social (emotion, eye gaze, and communication); (b) Speech (sounds and words); and (c) Symbolic (understanding and object use) and asks about developmental milestones. The data reported are the composite scores for these three categories. The possible scores for the three composite categories are as follows: Social Composite = 0-48; Speech Composite = 0-40; Symbolic Composite = 0-51. A higher score indicates more advanced abilities in that area.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Follow-up: Symbolic Composite Score	14.25 units on a scale Interval 9.0 to 16.0	18.00 units on a scale Interval 13.5 to 19.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 1 - First Intervention: Speech	4.00 units on a scale Interval 2.0 to 8.0	7.00 units on a scale Interval 2.0 to 10.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Follow-up: Social Composite Score	22.50 units on a scale Interval 18.0 to 25.0	28.00 units on a scale Interval 26.0 to 36.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 1 - First Intervention: Social	19.00 units on a scale Interval 16.0 to 25.0	22.00 units on a scale Interval 19.0 to 26.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 2: Social Composite Score	20.00 units on a scale Interval 15.0 to 23.0	24.00 units on a scale Interval 20.0 to 28.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 3: Social Composite Score	18.00 units on a scale Interval 13.0 to 25.0	24.00 units on a scale Interval 21.0 to 30.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 4: Social Composite Score	18.00 units on a scale Interval 17.0 to 25.0	24.00 units on a scale Interval 21.0 to 31.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 5: Social Composite Score	20.00 units on a scale Interval 15.0 to 29.0	23.00 units on a scale Interval 21.0 to 34.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 6 - Second Intervention: Social	18.00 units on a scale Interval 15.0 to 28.0	28.00 units on a scale Interval 22.0 to 34.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 7 - Second Intervention: Social	20.00 units on a scale Interval 16.0 to 26.0	25.00 units on a scale Interval 21.0 to 34.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 8 - Second Intervention: Social	21.00 units on a scale Interval 17.0 to 27.0	27.00 units on a scale Interval 25.0 to 36.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 9 - Second Intervention: Social	21.00 units on a scale Interval 17.0 to 29.0	29.00 units on a scale Interval 25.0 to 34.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 10 - Second Intervention: Social	22.50 units on a scale Interval 19.0 to 30.0	27.00 units on a scale Interval 23.0 to 36.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 2 - First Intervention: Speech	3.00 units on a scale Interval 1.0 to 9.0	5.00 units on a scale Interval 2.0 to 11.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 3 - First Intervention: Speech	5.00 units on a scale Interval 1.0 to 6.0	8.00 units on a scale Interval 2.0 to 11.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 4 - First Intervention: Speech	5.50 units on a scale Interval 3.0 to 8.5	5.00 units on a scale Interval 2.0 to 10.5
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 5 - First Intervention: Speech	6.50 units on a scale Interval 3.0 to 7.5	8.00 units on a scale Interval 2.0 to 11.5
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 6 - Second Intervention: Speech	4.00 units on a scale Interval 1.0 to 6.0	8.50 units on a scale Interval 2.0 to 11.5
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 7 - Second Intervention: Speech	4.00 units on a scale Interval 2.0 to 5.0	7.00 units on a scale Interval 4.0 to 12.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 8 - Second Intervention: Speech	5.00 units on a scale Interval 1.0 to 7.0	6.50 units on a scale Interval 2.0 to 9.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 9 - Second Intervention: Speech	5.00 units on a scale Interval 2.0 to 8.5	5.00 units on a scale Interval 2.0 to 10.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 10 - Second Intervention: Speech	5.00 units on a scale Interval 3.0 to 7.0	7.25 units on a scale Interval 2.5 to 11.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Follow-up: Speech Composite Score	6.00 units on a scale Interval 2.0 to 9.5	6.00 units on a scale Interval 2.0 to 10.5
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 1 - First Intervention: Symbolic	9.50 units on a scale Interval 6.5 to 12.5	14.00 units on a scale Interval 12.5 to 19.5
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 2 - First Intervention: Symbolic	10.50 units on a scale Interval 6.0 to 13.5	14.50 units on a scale Interval 11.0 to 17.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 3 - First Intervention: Symbolic	10.50 units on a scale Interval 4.0 to 13.0	15.00 units on a scale Interval 10.0 to 21.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 4 - First Intervention: Symbolic	12.00 units on a scale Interval 5.5 to 13.5	14.00 units on a scale Interval 11.5 to 22.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 5 - First Intervention: Symbolic	11.50 units on a scale Interval 7.0 to 17.5	16.50 units on a scale Interval 11.5 to 23.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 6 - Second Intervention: Symbolic	13.00 units on a scale Interval 6.5 to 15.0	18.50 units on a scale Interval 12.0 to 23.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 7 - Second Intervention: Symbolic	10.25 units on a scale Interval 6.0 to 13.0	17.00 units on a scale Interval 10.0 to 22.0
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 8 - Second Intervention: Symbolic	11.50 units on a scale Interval 6.5 to 15.5	17.00 units on a scale Interval 9.0 to 20.5
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 9 - Second Intervention: Symbolic	11.50 units on a scale Interval 9.0 to 18.5	18.00 units on a scale Interval 12.5 to 20.5
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP) Visit 10 - Second Intervention: Symbolic	13.75 units on a scale Interval 8.0 to 17.0	17.00 units on a scale Interval 11.0 to 19.0

SECONDARY outcome

Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

The ABC-C is a global behavior checklist implemented for the measurement of drug and other treatment effects in populations with intellectual disability. Behavior based on 58 items that describe various behavioral problems. Each item is rated on the parents perceived severity of the behavior. The answer options for each item are: 0 = Not a problem 1. = Problem but slight in degree 2. = Moderately serious problem 3. = Severe in degree The measure is broken down into the following subscales with individual ranges as follows: Subscale I (Irritability): 15 items, score range = 0-45 Subscale II (Lethargy): 16 items, score range = 0-48 Subscale III (Stereotypy): 7 items, score range = 0-21 Subscale IV (Hyperactivity): 16 items, score range = 0-48 Subscale V (Inappropriate Speech) was not included in the breakdown because it was not applicable (no participants in the study had verbal language).

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 6 - Second Intervention: Subscale IV	11.00 units on a scale Interval 7.0 to 22.0	7.00 units on a scale Interval 2.0 to 17.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 8 - Second Intervention: Subscale IV	7.00 units on a scale Interval 5.0 to 16.0	4.00 units on a scale Interval 0.0 to 11.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 10 - Second Intervention: Subscale IV	10.00 units on a scale Interval 4.0 to 20.0	5.00 units on a scale Interval 2.0 to 10.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Follow-up: Subscale IV (Hyperactivity)	9.00 units on a scale Interval 3.0 to 17.0	5.00 units on a scale Interval 1.0 to 9.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 1 - First Intervention: Subscale I	9.00 units on a scale Interval 6.0 to 22.0	6.00 units on a scale Interval 3.0 to 12.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 3 - First Intervention: Subscale I	9.00 units on a scale Interval 2.0 to 15.0	4.00 units on a scale Interval 0.0 to 7.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 5 - First Intervention: Subscale I	7.00 units on a scale Interval 0.0 to 16.0	2.00 units on a scale Interval 0.0 to 6.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 6 - Second Intervention: Subscale I	7.00 units on a scale Interval 3.0 to 13.0	4.00 units on a scale Interval 0.0 to 10.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 8 - Second Intervention: Subscale I	4.00 units on a scale Interval 1.0 to 17.0	3.00 units on a scale Interval 0.0 to 10.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 10 - Second Intervention: Subscale I	5.00 units on a scale Interval 2.0 to 14.0	5.00 units on a scale Interval 0.0 to 8.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Follow-up: Subscale I (Irritability)	3.00 units on a scale Interval 0.0 to 9.0	2.00 units on a scale Interval 0.0 to 7.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 1 - First Intervention: Subscale II	13.00 units on a scale Interval 5.0 to 19.0	8.00 units on a scale Interval 4.0 to 10.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 3 - First Intervention: Subscale II	11.00 units on a scale Interval 3.0 to 17.0	7.00 units on a scale Interval 3.0 to 8.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 5 - First Intervention: Subscale II	9.00 units on a scale Interval 5.0 to 12.0	6.00 units on a scale Interval 4.0 to 10.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 6 - Second Intervention: Subscale II	11.00 units on a scale Interval 5.0 to 16.0	5.00 units on a scale Interval 2.0 to 9.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 8 - Second Intervention: Subscale II	8.00 units on a scale Interval 4.0 to 11.0	5.00 units on a scale Interval 2.0 to 9.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 10 - Second Intervention: Subscale II	6.00 units on a scale Interval 4.0 to 9.0	4.00 units on a scale Interval 2.0 to 6.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Follow-up: Subscale II (Lethargy)	6.00 units on a scale Interval 2.0 to 11.0	5.00 units on a scale Interval 2.0 to 8.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 1 - First Intervention: Subscale III	13.00 units on a scale Interval 10.0 to 16.0	12.00 units on a scale Interval 9.0 to 14.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 3 - First Intervention: Subscale III	10.00 units on a scale Interval 8.0 to 15.0	10.00 units on a scale Interval 8.0 to 13.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 5 - First Intervention: Subscale III	11.00 units on a scale Interval 9.0 to 16.0	9.00 units on a scale Interval 7.0 to 12.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 6 - Second Intervention: Subscale III	11.00 units on a scale Interval 7.0 to 16.0	11.00 units on a scale Interval 9.0 to 12.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 8 - Second Intervention: Subscale III	10.00 units on a scale Interval 7.0 to 15.0	9.00 units on a scale Interval 7.0 to 11.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 10 - Second Intervention: Subscale III	8.00 units on a scale Interval 6.0 to 12.0	9.00 units on a scale Interval 7.0 to 12.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Follow-up: Subscale III (Stereotypy)	8.00 units on a scale Interval 6.0 to 11.0	9.00 units on a scale Interval 7.0 to 12.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 1 - First Intervention: Subscale IV	13.00 units on a scale Interval 8.0 to 22.0	8.00 units on a scale Interval 6.0 to 14.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 3 - First Intervention: Subscale IV	12.00 units on a scale Interval 7.0 to 15.0	8.00 units on a scale Interval 3.0 to 13.0
Aberrant Behavior Checklist - Community Edition (ABC-C) Visit 5 - First Intervention: Subscale IV	11.00 units on a scale Interval 8.0 to 26.0	6.00 units on a scale Interval 3.0 to 6.0

SECONDARY outcome

Timeframe: Every 10 weeks during each of the two 20-week treatment periods

Population: In some cases, the number of participants analyzed is less than 15 for each group due to inability to complete testing session. One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

Respiratory data was collected using non-invasive respiratory inductance plethysmography from a BioCapture® recording device. BioCapture® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It can be configured with the pediatric chest and abdominal plethysmography bands and the 3 lead ECG signals we plan to use for monitoring cardiac safety throughout the study. Each transducer is placed on the patient independently to provide a customized fit that yields the highest signal quality for each patient irrespective of body shape and proportion. The transducer signals captured by the BioCapture® are transmitted wirelessly to a laptop computer where all signals are displayed in real-time. The apnea index is given as apneas/hour. Data on apneas greater than or equal to 10 seconds are displayed below. The higher the frequency of apnea, the more severe the breathing abnormality.

Outcome measures

Outcome measures
Measure	Placebo First, Then rhIGF-1 n=15 Participants One half of subjects will be randomly assigned to receive placebo during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of a saline solution (placebo).	rhIGF-1 First, Then Placebo n=15 Participants One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) during the first arm of the study. Subjects assigned to this group will receive twice daily subcutaneous injections of IGF-1.
Quantitative Measures of Respiration: Apnea Index Visit 10 - Second Intervention: Apnea Index	8.91 Apneas/Hour Interval 4.13 to 14.34	5.56 Apneas/Hour Interval 1.57 to 13.47
Quantitative Measures of Respiration: Apnea Index Visit 1 - First Intervention: Apnea Index	7.58 Apneas/Hour Interval 1.58 to 10.33	4.05 Apneas/Hour Interval 2.07 to 7.91
Quantitative Measures of Respiration: Apnea Index Visit 3 - First Intervention: Apnea Index	4.80 Apneas/Hour Interval 0.38 to 9.2	3.48 Apneas/Hour Interval 2.0 to 4.19
Quantitative Measures of Respiration: Apnea Index Visit 5 - First Intervention: Apnea Index	6.93 Apneas/Hour Interval 3.06 to 9.07	3.07 Apneas/Hour Interval 0.4 to 5.11
Quantitative Measures of Respiration: Apnea Index Visit 6 - Second Intervention: Apnea Index	7.90 Apneas/Hour Interval 4.3 to 17.6	3.62 Apneas/Hour Interval 2.2 to 11.82
Quantitative Measures of Respiration: Apnea Index Visit 8 - Second Intervention: Apnea Index	7.28 Apneas/Hour Interval 2.8 to 12.53	5.55 Apneas/Hour Interval 1.24 to 12.81

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 16 other events

Deaths: 0 deaths

rhIGF-1

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Off Treatment

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=30 participants at risk This group includes subjects who had a reported Adverse Event (AE) while they were receiving placebo treatment.	rhIGF-1 n=30 participants at risk This group includes subjects who had a reported Adverse Event (AE) while they were receiving rhIGF-1 treatment.	Off Treatment n=30 participants at risk This group includes subjects who had a reported Adverse Event (AE) while they were not receiving any treatment. This includes the period between Screening and Baseline, the 20-week washout period between study arms, and the 12-week follow up period after study completion.
Gastrointestinal disorders Colitis	0.00% 0/15 • 80 weeks (from screening visit to 12-week follow up phone call).	6.7% 1/15 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Seizure	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Pneumonia	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).	6.7% 2/30 • Number of events 3 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).

Other adverse events

Additional Information

Dr. Mustafa Sahin, Director of Translational Neuroscience Center

Boston Children's Hospital

Phone: 617-919-6258

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=30 participants at risk This group includes subjects who had a reported Adverse Event (AE) while they were receiving placebo treatment.	rhIGF-1 n=30 participants at risk This group includes subjects who had a reported Adverse Event (AE) while they were receiving rhIGF-1 treatment.	Off Treatment n=30 participants at risk This group includes subjects who had a reported Adverse Event (AE) while they were not receiving any treatment. This includes the period between Screening and Baseline, the 20-week washout period between study arms, and the 12-week follow up period after study completion.
Cardiac disorders Abnormal ECG - Prolonged QT	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).
Surgical and medical procedures Adenoidectomy	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Endocrine disorders Advanced Bone Age	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Psychiatric disorders Anxiety	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Musculoskeletal and connective tissue disorders Fracture	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Conjunctivitis	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Lung Infection	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Ear and labyrinth disorders Otitis Media	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).	13.3% 4/30 • Number of events 4 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Pharyngitis	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Pneumonia	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Endocrine disorders Precocious Puberty	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
Respiratory, thoracic and mediastinal disorders Sleep Apnea	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
Gastrointestinal disorders Vomiting	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
Musculoskeletal and connective tissue disorders Scoliosis	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Seizures	10.0% 3/30 • Number of events 4 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Seizure and Fever	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Seizure and vomiting	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Sinusitis	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	13.3% 4/30 • Number of events 4 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
Gastrointestinal disorders Vomiting and Diarrhea	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Gastrointestinal disorders Constipation	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Respiratory, thoracic and mediastinal disorders Cough	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Gastrointestinal disorders Diarrhea	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Fever	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Elevated Alkaline Phosphatase	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Alopecia	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	6.7% 2/30 • Number of events 2 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Dysphagia	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Gastrointestinal disorders Dyspepsia	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Skin and subcutaneous tissue disorders Eczema	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Gastrointestinal disorders Gastroenteritis	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Productive Cough and Vomiting	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Car Accident	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
Nervous system disorders Extrapyramidal Disorder	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Skin and subcutaneous tissue disorders Facial Swelling	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Fall	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
Surgical and medical procedures Gastrostomy Tube Replacement	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Hand, Foot, and Mouth Disease	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Injection Site Reaction	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
General disorders Minor Head Injury	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Cardiac disorders Other Cardiac Disorder	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).
Psychiatric disorders Personality Disorder	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Skin and subcutaneous tissue disorders Rash	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Skin (Eye) Infection	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Skin and subcutaneous tissue disorders Skin Abscess	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Immune system disorders Tonsillar Hypertrophy	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Musculoskeletal and connective tissue disorders Unequal limb length	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Infections and infestations Upper Respiratory Infection	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).
Metabolism and nutrition disorders Anorexia	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	0.00% 0/30 • 80 weeks (from screening visit to 12-week follow up phone call).	3.3% 1/30 • Number of events 1 • 80 weeks (from screening visit to 12-week follow up phone call).