Trial Outcomes & Findings for A Trial of Sertraline in Young Children With Autism Spectrum Disorder (NCT NCT02385799)

Last Updated: 2019-10-22

Results Overview

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the baseline and 6-month follow-up raw scores from the expressive language scale. This scale's raw scores range from 0 to 50. The lower the score on this scale, the weaker the ability; the higher the score, the greater the ability. The MSEL was administered at the baseline visit and at the 6-month follow-up visit.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

58 participants

Primary outcome timeframe

From baseline visit to six-month visit

Results posted on

2019-10-22

Participant Flow

Participant milestones

Participant milestones
Measure	Sertraline Liquid Placebo The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Overall Study STARTED	26	32
Overall Study Completed End-of-Treatment Visit	21	26
Overall Study COMPLETED	21	24
Overall Study NOT COMPLETED	5	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Sertraline Liquid Placebo The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Overall Study Lost to Follow-up	1	2
Overall Study Adverse Event	4	2
Overall Study Withdrawal by Subject	0	4

Baseline Characteristics

A Trial of Sertraline in Young Children With Autism Spectrum Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sertraline Liquid Placebo n=26 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=32 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication	Total n=58 Participants Total of all reporting groups
Age, Categorical <=18 years	26 Participants n=5 Participants	32 Participants n=7 Participants	58 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	3.70 years STANDARD_DEVIATION 1.10 • n=5 Participants	4.31 years STANDARD_DEVIATION 0.90 • n=7 Participants	4.005 years STANDARD_DEVIATION 1.00 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	25 Participants n=7 Participants	46 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	29 Participants n=7 Participants	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	32 participants n=7 Participants	58 participants n=5 Participants
The Autism Diagnostic Observation Schedule-Second Edition (ADOS-2)	7.88 units on a scale STANDARD_DEVIATION 1.62 • n=5 Participants	7.34 units on a scale STANDARD_DEVIATION 1.58 • n=7 Participants	7.58 units on a scale STANDARD_DEVIATION 1.60 • n=5 Participants

PRIMARY outcome

Timeframe: From baseline visit to six-month visit

Population: Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned voluntarily to complete follow-up assessments, so 26 subjects were analyzed at follow-up.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=26 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=32 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Change in Mullen Scales of Early Learning - Expressive Language Raw Score Baseline	19.69 score on a scale Standard Deviation 11.69	18.19 score on a scale Standard Deviation 10.39
Change in Mullen Scales of Early Learning - Expressive Language Raw Score Follow-up	21.81 score on a scale Standard Deviation 14.29	20.31 score on a scale Standard Deviation 11.70

PRIMARY outcome

Timeframe: From baseline visit to six-month visit

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the baseline and 6-month follow-up combined age equivalent scores, calculated as the sum of the age equivalent scores from each scale. The combined score ranges from 0 to 280. The lower the score on this scale, the weaker the ability; the higher the score, the greater the ability. The MSEL was administered at the baseline visit and at the 6-month follow-up visit.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=26 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=32 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Change in Mullen Scales of Early Learning - Combined Age Equivalent Score Baseline	25.61 score on a scale Standard Deviation 11.73	24.98 score on a scale Standard Deviation 12.79
Change in Mullen Scales of Early Learning - Combined Age Equivalent Score Follow-up	30.30 score on a scale Standard Deviation 15.58	28.16 score on a scale Standard Deviation 14.15

SECONDARY outcome

Timeframe: At baseline visit

The Vineland-II measures the personal and social skills of individuals from birth through adulthood. It was designed to assess handicapped and non-handicapped persons in their personal and social functioning and is appropriate for individuals of all ages. The Vineland-II is a survey that is administered to a parent or caregiver using a semi-structured interview format and is organized around four Behavior Domains: Communication, Daily Living Skills, Socialization, and Motor Skills. Each subtest is scored with a standard score X=100 ± 15 and summed to calculate the Adaptive Behavior Composite (ABC) using age-adjusted scoring tables. Reported here are the ABC mean standard scores for the placebo and treatment groups at baseline. The ABC ranges from 20 to 160 and indicates low (20-70), moderately low (70-85), adequate (85-115), moderately high (115-130), or high (130-160) overall adaptive functioning.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=26 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=32 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Adaptive Behavior Composite Standard Score	68.50 score on a scale Standard Deviation 11.14	60.03 score on a scale Standard Deviation 12.15

SECONDARY outcome

Timeframe: At six-month visit

Population: Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned for an end-of-treatment visit, but due to time limitations only 1 of these 2 completed this assessment, so 25 subjects were analyzed at follow-up.

The Vineland-II measures the personal and social skills of individuals from birth through adulthood. It was designed to assess handicapped and non-handicapped persons in their personal and social functioning and is appropriate for individuals of all ages. The Vineland-II is a survey that is administered to a parent or caregiver using a semi-structured interview format and is organized around four Behavior Domains: Communication, Daily Living Skills, Socialization, and Motor Skills. Each subtest is scored with a standard score X=100 ± 15 and summed to calculate the Adaptive Behavior Composite (ABC) using age-adjusted scoring tables. Reported here are the ABC mean standard scores for the placebo and treatment groups at the six-month visit. The ABC ranges from 20 to 160 and indicates low (20-70), moderately low (70-85), adequate (85-115), moderately high (115-130), or high (130-160) overall adaptive functioning.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=21 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=25 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Adaptive Behavior Composite Standard Score	71.52 score on a scale Standard Deviation 15.47	69.68 score on a scale Standard Deviation 15.14

SECONDARY outcome

Timeframe: At baseline visit

Population: Placebo group: staff inadvertently neglected to administer this questionnaire to the 2 subjects' caregivers at baseline, so only 24 were completed.

Preschool Anxiety Scale-Revised (PAS-R) is a questionnaire designed to assess symptoms of anxiety and fears in young children aged 6 and below as reported by their parents. The PAS-R consists of 34 questions, each with a rating option of 0 to 4 where 0=not true at all, 1=seldom true, 2=sometimes true, 3=quite often true, and 4=very often true. The total score is calculated as the sum of all responses and therefore ranges from 0 to 136. Lower scores indicate less anxiety/fear; higher scores indicate more anxiety/fear. Reported here are the mean total scores for the placebo and treatment groups at baseline.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=24 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=32 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Preschool Anxiety Scale-Revised - Total Score	15.38 score on a scale Standard Deviation 12.51	14.75 score on a scale Standard Deviation 11.58

SECONDARY outcome

Timeframe: At six-month visit

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=21 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=26 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Preschool Anxiety Scale-Revised - Total Score	11.43 score on a scale Standard Deviation 10.04	14.77 score on a scale Standard Deviation 14.45

SECONDARY outcome

Timeframe: At baseline visit

Population: Sertraline group: 2 subjects were completely nonverbal at baseline, so the rater determined that their assessments could not be completed; therefore, only 30 subjects in this arm were analyzed at baseline.

The Preschool Language Scale-Fifth Edition (PLS-5) is designed to measure auditory comprehension (AC) and expressive communication (EC) for children from birth to 7 years 11 months. The measure examines the child's attention, play, gestures, social communication, semantics, language structure, integrative language skills and emergent literacy skills. The PLS-5 has expanded coverage of early play behaviors, concepts, theory of mind, and emergent literacy skills. The PLS-5 yields norm-referenced scores including standard scores, percentile ranks and age equivalents for the AC and EC scales as well as for Total Language (TL). Raw score ranges are 0 to 65 in AC, 0 to 67 in EC, and therefore 0 to 132 in TL (calculated by summing AC+EC raw scores). The higher the scores, the greater the language ability. Shown here are the mean TL raw scores from the baseline visit.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=26 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=30 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Preschool Language Scale-Fifth Edition - Total Language Raw Score	48.65 score on a scale Standard Deviation 25.57	43.03 score on a scale Standard Deviation 23.35

SECONDARY outcome

Timeframe: At six-month visit

Population: Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned for an end-of-treatment visit, but due to time limitations only 1 of these 2 completed this assessment, so 25 subjects were analyzed at follow-up.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=21 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=25 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Preschool Language Scale-Fifth Edition - Total Language Raw Score	57.24 score on a scale Standard Deviation 26.26	51.40 score on a scale Standard Deviation 23.56

SECONDARY outcome

Timeframe: At baseline visit

Population: Placebo group: staff inadvertently neglected to administer this questionnaire to 1 subject's caregiver at baseline, so only 25 were completed. Sertraline group: staff inadvertently neglected to administer this questionnaire to 1 subject's caregiver at baseline, so only 31 were completed.

The Sensory Processing Measure-Preschool (SPM-P) is a questionnaire measuring specific problems, including under- and over-responsiveness, sensory-seeking behavior, and perceptual problems in multiple environments (at home, at school, and in the community) for children aged 2 to 5 years old, as reported by the parent/caregiver. The SPM-P provides norm-referenced standard scores for two higher-level integrative functions (praxis and social participation) and five sensor sensory systems (visual, auditory, tactile, proprioceptive, and vestibular functioning). Reported here is the Social Participation subscale mean raw score at baseline, which ranges from 8 to 32. The lower the raw score, the more limited the child's level of social participation. The higher the score, the greater the child's level of social participation.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=25 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=31 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Sensory Processing Measure-Preschool - Social Participation Raw Score	21.96 score on a scale Standard Deviation 3.81	22.39 score on a scale Standard Deviation 5.10

SECONDARY outcome

Timeframe: At six-month visit

Population: Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned for an end-of-treatment visit, but due to time limitations only 1 of these 2 completed this assessment, so 25 subjects were analyzed at follow-up.

The Sensory Processing Measure-Preschool (SPM-P) is a questionnaire measuring specific problems, including under- and over-responsiveness, sensory-seeking behavior, and perceptual problems in multiple environments (at home, at school, and in the community) for children aged 2 to 5 years old, as reported by the parent/caregiver. The SPM-P provides norm-referenced standard scores for two higher-level integrative functions (praxis and social participation) and five sensor sensory systems (visual, auditory, tactile, proprioceptive, and vestibular functioning). Reported here is the Social Participation subscale mean raw score at the six-month visit, which ranges from 8 to 32. The lower the raw score, the more limited the child's level of social participation. The higher the score, the greater the child's level of social participation.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=21 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=25 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Sensory Processing Measure-Preschool - Social Participation Raw Score	20.86 score on a scale Standard Deviation 4.07	21.16 score on a scale Standard Deviation 5.04

SECONDARY outcome

Timeframe: At baseline visit

The Clinical Global Impression-Severity (CGI-S) is a 7-point scale completed by a clinician that yields a rating of the patient's illness severity at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The 7-point scale ranges from: 1 = Normal; 2 = Borderline Ill; 3 = Mildly Ill; 4 = Moderately Ill; 5 = Markedly Ill; 6 = Severely Ill; and 7 = Extremely Ill. Therefore, the higher the score, the greater the severity of the patient's illness. The CGI-S was administered at baseline only for the purpose of characterizing the study population. Shown here are the CGI-S mean scores from the baseline visit.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=26 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=32 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Clinical Global Impression Scale-Severity (CGI-S)	4.38 score on a scale Standard Deviation 0.98	4.66 score on a scale Standard Deviation 0.94

SECONDARY outcome

Timeframe: At three-month visit

Population: Placebo group: 3 discontinued treatment/become lost to follow-up prior to reaching 3-month visit, so 23 subjects were analyzed at this timepoint. Sertraline group: 5 discontinued treatment/become lost to follow-up prior to reaching 3-month visit, so 27 subjects were analyzed at this timepoint.

The Clinical Global Impression-Improvement (CGI-I) is a 7-point scale completed by a clinician that yields a score measuring the overall behavioral change of an individual and their therapeutic response. The 7-point scale ranges from: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse. Therefore, the lower the score, the greater the behavioral improvement as rated by the clinician. The CGI-I was administered at the three-month and six-month visits. Shown here are the CGI-I mean scores from the 3-month follow-up visit.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=23 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=27 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Clinical Global Impression Scale-Improvement (CGI-I)	2.65 score on a scale Standard Deviation 1.11	2.70 score on a scale Standard Deviation 1.03

SECONDARY outcome

Timeframe: At six-month visit

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=21 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=26 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Clinical Global Impression Scale-Improvement (CGI-I)	1.14 score on a scale Standard Deviation 0.96	1.23 score on a scale Standard Deviation 1.11

SECONDARY outcome

Timeframe: At baseline visit

Population: Placebo group: staff inadvertently neglected to administer this assessment to 1 subject's caregiver at baseline, so only 25 were completed. Sertraline group: staff inadvertently neglected to administer this assessment to 1 subject's caregiver at baseline, so only 31 were completed.

The Visual Analog Scale measures the severity of three specific behavioral symptoms as reported by the parent/caregiver: Language/Communication, Anxiety/Obsessive Compulsive Behaviors, and Aggression/Hyperactivity/Hyperarousal. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the six-month visit. The calculated distance in cm between the marks drawn at the baseline and six-month visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Language/Communication scale, at baseline. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=25 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=31 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Visual Analog Scale - Language/Communication Score	2.84 centimeters Standard Deviation 2.04	2.03 centimeters Standard Deviation 1.70

SECONDARY outcome

Timeframe: At six-month visit

Population: Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned for an end-of-treatment visit, but due to time limitations only 1 of these 2 completed this assessment, so 25 subjects were analyzed at follow-up.

The Visual Analog Scale measures the severity of three specific behavioral symptoms as reported by the parent/caregiver: Language/Communication, Anxiety/Obsessive Compulsive Behaviors, and Aggression/Hyperactivity/Hyperarousal. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the six-month visit. The calculated distance in cm between the marks drawn at the baseline and six-month visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Language/Communication scale, at the six-month visit. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.

Outcome measures

Outcome measures
Measure	Sertraline Liquid Placebo n=21 Participants The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=25 Participants Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Visual Analog Scale - Language/Communication Score	5.53 centimeters Standard Deviation 2.95	4.70 centimeters Standard Deviation 2.73

Adverse Events

Sertraline Liquid Placebo

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Sertraline Active Medication

Serious events: 1 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sertraline Liquid Placebo n=26 participants at risk The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=32 participants at risk Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Infections and infestations Hospitalization for dehydration	0.00% 0/26 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).

Other adverse events

Additional Information

Dr. Randi Hagerman

UC Davis MIND Institute

Phone: 916-703-0247

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Sertraline Liquid Placebo n=26 participants at risk The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Sertraline Active Medication n=32 participants at risk Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Infections and infestations Upper respiratory infection	73.1% 19/26 • Number of events 39 • From baseline to follow-up (6 months).	71.9% 23/32 • Number of events 48 • From baseline to follow-up (6 months).
Gastrointestinal disorders Diarrhea	57.7% 15/26 • Number of events 17 • From baseline to follow-up (6 months).	25.0% 8/32 • Number of events 11 • From baseline to follow-up (6 months).
Psychiatric disorders Hyperactivity	34.6% 9/26 • Number of events 13 • From baseline to follow-up (6 months).	37.5% 12/32 • Number of events 14 • From baseline to follow-up (6 months).
Psychiatric disorders Sleep disturbance	11.5% 3/26 • Number of events 3 • From baseline to follow-up (6 months).	31.2% 10/32 • Number of events 14 • From baseline to follow-up (6 months).
Psychiatric disorders Irritability/Aggression	38.5% 10/26 • Number of events 11 • From baseline to follow-up (6 months).	21.9% 7/32 • Number of events 9 • From baseline to follow-up (6 months).
Infections and infestations Fever	26.9% 7/26 • Number of events 8 • From baseline to follow-up (6 months).	18.8% 6/32 • Number of events 10 • From baseline to follow-up (6 months).
Gastrointestinal disorders Vomiting	11.5% 3/26 • Number of events 3 • From baseline to follow-up (6 months).	21.9% 7/32 • Number of events 9 • From baseline to follow-up (6 months).
Gastrointestinal disorders Gastroenteritis	19.2% 5/26 • Number of events 7 • From baseline to follow-up (6 months).	21.9% 7/32 • Number of events 7 • From baseline to follow-up (6 months).
Infections and infestations Otitis media	7.7% 2/26 • Number of events 2 • From baseline to follow-up (6 months).	15.6% 5/32 • Number of events 7 • From baseline to follow-up (6 months).
Skin and subcutaneous tissue disorders Rash	15.4% 4/26 • Number of events 6 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Psychiatric disorders Lethargy	15.4% 4/26 • Number of events 5 • From baseline to follow-up (6 months).	9.4% 3/32 • Number of events 3 • From baseline to follow-up (6 months).
Nervous system disorders Tic	0.00% 0/26 • From baseline to follow-up (6 months).	6.2% 2/32 • Number of events 4 • From baseline to follow-up (6 months).
Gastrointestinal disorders Constipation	11.5% 3/26 • Number of events 3 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 2 • From baseline to follow-up (6 months).
Immune system disorders Seasonal allergies	7.7% 2/26 • Number of events 3 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Gastrointestinal disorders Decreased appetite	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	9.4% 3/32 • Number of events 3 • From baseline to follow-up (6 months).
Eye disorders Dilated pupils	3.8% 1/26 • Number of events 2 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Eye disorders Eye redness	7.7% 2/26 • Number of events 2 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Psychiatric disorders Obsessive behaviors	7.7% 2/26 • Number of events 2 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Psychiatric disorders Self-injurious behavior	3.8% 1/26 • Number of events 2 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Gastrointestinal disorders Encopresis	0.00% 0/26 • From baseline to follow-up (6 months).	6.2% 2/32 • Number of events 2 • From baseline to follow-up (6 months).
Psychiatric disorders Increased stimming	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	6.2% 2/32 • Number of events 2 • From baseline to follow-up (6 months).
Psychiatric disorders Mouthing/chewing objects	0.00% 0/26 • From baseline to follow-up (6 months).	6.2% 2/32 • Number of events 2 • From baseline to follow-up (6 months).
Psychiatric disorders Regression	0.00% 0/26 • From baseline to follow-up (6 months).	6.2% 2/32 • Number of events 2 • From baseline to follow-up (6 months).
Psychiatric disorders Teeth grinding	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	6.2% 2/32 • Number of events 2 • From baseline to follow-up (6 months).
Injury, poisoning and procedural complications Cut	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Renal and urinary disorders Enuresis	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Nervous system disorders Excessive drooling	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Infections and infestations Hand Foot Mouth Disease	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Nervous system disorders Headaches	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Psychiatric disorders Increase in pica	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Skin and subcutaneous tissue disorders Itching	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Immune system disorders Localized left leg swelling	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Nervous system disorders Gray matter heterotopia	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Ear and labyrinth disorders PE tube surgery	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Nervous system disorders Possible seizure/syncope	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Psychiatric disorders Separation anxiety	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Injury, poisoning and procedural complications Sprained ankle	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Infections and infestations Staph infection	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Congenital, familial and genetic disorders Tuberous sclerosis	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Renal and urinary disorders Urinary retention	3.8% 1/26 • Number of events 1 • From baseline to follow-up (6 months).	0.00% 0/32 • From baseline to follow-up (6 months).
Skin and subcutaneous tissue disorders Burned feet	0.00% 0/26 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Infections and infestations Chicken pox	0.00% 0/26 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Infections and infestations Flu	0.00% 0/26 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Gastrointestinal disorders Gas	0.00% 0/26 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Psychiatric disorders Hoarding	0.00% 0/26 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Psychiatric disorders Inappropriate laughing	0.00% 0/26 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Psychiatric disorders Inattention	0.00% 0/26 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Gastrointestinal disorders Increased frequency of bowel movements	0.00% 0/26 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).
Musculoskeletal and connective tissue disorders Tooth pain	0.00% 0/26 • From baseline to follow-up (6 months).	3.1% 1/32 • Number of events 1 • From baseline to follow-up (6 months).