Trial Outcomes & Findings for Novel Approach to Stimulant Induced Weight Suppression and Its Impact on Growth (NCT NCT01109849)

NCT ID: NCT01109849

Last Updated: 2017-07-14

Results Overview

The primary endpoint will be change in z-height at month 30 which is study endpoint. Measured as a zscore with more negative units reflecting smaller incremental height gain. Z units used to account for differences between groups in gender and age with both impact height at a fixed time.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 230 participants
• Primary outcome timeframe: month 30 or last assessment point
• Results posted on: 2017-07-14

Participant Flow

Participant milestones

Measure	Behavior Therapy 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation	ER Stimulant daily use of 12 hour extended release (ER) methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Caloric Supplementation Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks, continuation of a daily extended release stimulant and the addition of a liquid 8oz caloric supplement every evening.	Drug Holiday Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and limiting CNS stimulant medication to school days only.	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Initial Randomization: ADHD Treatment STARTED	50	180	0	0	0
Initial Randomization: ADHD Treatment COMPLETED	32	131	0	0	0
Initial Randomization: ADHD Treatment NOT COMPLETED	18	49	0	0	0
Adaptive Randomization: Weight Recovery STARTED	0	0	24	23	25
Adaptive Randomization: Weight Recovery COMPLETED	0	0	23	20	24
Adaptive Randomization: Weight Recovery NOT COMPLETED	0	0	1	3	1

Reasons for withdrawal

Measure	Behavior Therapy 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation	ER Stimulant daily use of 12 hour extended release (ER) methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Caloric Supplementation Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks, continuation of a daily extended release stimulant and the addition of a liquid 8oz caloric supplement every evening.	Drug Holiday Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and limiting CNS stimulant medication to school days only.	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Initial Randomization: ADHD Treatment Lost to Follow-up	9	35	0	0	0
Initial Randomization: ADHD Treatment Protocol Violation	1	0	0	0	0
Initial Randomization: ADHD Treatment Withdrawal by Subject	6	7	0	0	0
Initial Randomization: ADHD Treatment move away	2	7	0	0	0
Adaptive Randomization: Weight Recovery Lost to Follow-up	0	0	1	1	1
Adaptive Randomization: Weight Recovery moved away	0	0	0	2	0

Baseline Characteristics

Novel Approach to Stimulant Induced Weight Suppression and Its Impact on Growth

Baseline characteristics by cohort

Measure	Behavior Therapy n=50 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation	ER Stimulant n=180 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Total n=230 Participants Total of all reporting groups
Age, Continuous	8.54 years STANDARD_DEVIATION 2.28 • n=5 Participants	8.15 years STANDARD_DEVIATION 1.86 • n=7 Participants	8.23 years STANDARD_DEVIATION 1.96 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	47 Participants n=7 Participants	61 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	133 Participants n=7 Participants	169 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	35 Participants n=5 Participants	134 Participants n=7 Participants	169 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	46 Participants n=7 Participants	61 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	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	17 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) White	45 Participants n=5 Participants	157 Participants n=7 Participants	202 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	3 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	50 participants n=5 Participants	180 participants n=7 Participants	230 participants n=5 Participants
zHeight	0.01 Z score STANDARD_DEVIATION 1.00 • n=5 Participants	0.09 Z score STANDARD_DEVIATION 0.99 • n=7 Participants	0.07 Z score STANDARD_DEVIATION 0.99 • n=5 Participants
zWeight	.350 Z score STANDARD_DEVIATION .918 • n=5 Participants	.277 Z score STANDARD_DEVIATION .912 • n=7 Participants	0.314 Z score STANDARD_DEVIATION 0.90 • n=5 Participants
zBMI	0.581 Z score STANDARD_DEVIATION 0.825 • n=5 Participants	0.384 Z score STANDARD_DEVIATION 0.837 • n=7 Participants	0.424 Z score STANDARD_DEVIATION 0.85 • n=5 Participants

PRIMARY outcome

Timeframe: month 30 or last assessment point

Population: includes all with 2+ growth assessments from the behavior therapy and ER stimulant arms. Doesn't include adaptive randomization arms (drug holiday, cal supplement, monitoring) as they didn't exist until 2nd randomization. See outcome #10 for change in zht from beginning to end of second randomization.

The primary endpoint will be change in z-height at month 30 which is study endpoint.

Measured as a zscore with more negative units reflecting smaller incremental height gain. Z units used to account for differences between groups in gender and age with both impact height at a fixed time.

Outcome measures

Measure	Behavior Therapy n=42 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=170 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change Score for Z-height Baseline to Endpoint	-.04 Z score Standard Deviation .46	-.11 Z score Standard Deviation .41	—

SECONDARY outcome

Timeframe: baseline to month 30 or to last assessment point

Population: includes all with 2+ growth assessments from the behavior therapy and ER stimulant arms. Doesn't include adaptive randomization arms (drug holiday, caloric supplement, monitoring) as they did not exist until 2nd randomization. See outcome #11 for change in zwt from beginning to end of second randomization.

difference between baseline and endpoint (month 30 or last assessment point if did not finish study). Measured as a zscore with more negative units reflecting lesser weight gain. Z units used to account for differences between groups in gender and age with both impact weight at a fixed time.

Outcome measures

Measure	Behavior Therapy n=42 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=170 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change Score for z Weight	-.01 Z score Standard Deviation .56	-.19 Z score Standard Deviation .45	—

SECONDARY outcome

Timeframe: baseline to month 30 or last assessment point

Population: includes all with 2+ growth assessments from the behavior therapy and ER stimulant arms. Doesn't include adaptive randomization arms (drug holiday, caloric supplement, monitoring) as they did not exist until 2nd randomization. See outcome #12 for change in zBMI from beginning to end of second randomization.

BMI will be calculated at endpoint (month 30). Difference between baseline and endpoint (month 30 or last assessment point if did not finish study). Measured as a zscore with more negative units reflecting less BMI gain. Z units used to account for differences between groups in gender and age with both impact BMI at a fixed time.

Outcome measures

Measure	Behavior Therapy n=42 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=170 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change in zBody Mass Index (BMI)	-.06 Z score Standard Deviation .53	-.21 Z score Standard Deviation .51	—

SECONDARY outcome

Timeframe: from entry to exit of caloric supplement arm

Population: those assigned to caloric supplement group

percent of days caloric supplement were taken versus prescribed in caloric supplement arm

Outcome measures

Measure	Behavior Therapy n=24 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Treatment Adherence for Caloric Supplement	70 percentage of days Standard Deviation 29.4	—	—

SECONDARY outcome

Timeframe: at month 30 or last collected assessment point

Population: those assigned to either Behavior therapy or ER stimulant with at least one post baseline assessment of ADHD symptoms. Second randomization arms (drug holiday, cal supplement, monitoring) not included as only relevant outcomes are ht, wt and BMI. All subjects in these arms are either in behavior therapy or er stimulant arm from 1st randomization.

sum of score on 10 item IOWA Conners with range from 0 to 30 and higher values indicating more symptoms. Collected at end point or last assessment point.

Outcome measures

Measure	Behavior Therapy n=46 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=175 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
ADHD Symptoms- Parent Rated	15.6 units on a scale Standard Deviation 6.7	15.2 units on a scale Standard Deviation 5.7	—

SECONDARY outcome

Timeframe: baseline to month 6

Population: participants with at height measurement at month 6

in addition to the primary outcome of height at month 30, change in z-height from baseline to study month 6 post is also reported. Subjects who were still moderately impaired after 6 months in their initial treatment arm were allowed to cross over and receive the treatments in the other arm so prior to month 6 no participants randomized to behavior arm were prescribed study medication.

This outcome includes all participants with 2+ growth assessments from the behavior therapy and ER stimulant arms. Doesn't include adaptive randomization arms (drug holiday, cal supplement, monitoring) as they didn't exist until 2nd randomization which did not occur until after this assessment period was over.

Height converted to z score to account for differences in age and gender. More negative values reflecting smaller incremental height gain.

If participant dropped out prior to month 6, then the last assessment point was used.

Outcome measures

Measure	Behavior Therapy n=42 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=170 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change Score for Zheight Months 0 to 6	0.00 Z score Standard Deviation 0.19	-0.035 Z score Standard Deviation 0.14	—

SECONDARY outcome

Timeframe: month 30 or last assessment point

Population: those assigned to either Behavior therapy or ER stimulant with at least one post baseline assessment of ADHD symptoms. Second randomization arms (drug holiday, cal supplement, monitoring) not included as only relevant outcomes are ht, wt and BMI. All subjects in these arms are either in behavior therapy or er stimulant arm from 1st randomization.

sum of items on 10 item IOWA Conners with range from 0-30 and larger values indicating greater symptoms. Collected at endpoint or last assessment point.

Outcome measures

Measure	Behavior Therapy n=42 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=167 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
ADHD Symptoms- Teacher Rated	14.5 units on a scale Standard Deviation 7.2	13.8 units on a scale Standard Deviation 7.7	—

SECONDARY outcome

Timeframe: denominator is number of days in study for which study med was prescribed

Population: any participants with at least one dose of med prescribed. The second randomization arms are not included as all participants in those arms are derived from these two groups and this assessment period includes the entire duration of the second randomization. Also, the second randomization addressees weight gain, not ADHD treatment.

% of study days that study ADHD medication was taken when prescribed to be taken; behavior group could be prescribed medication if moderately impaired still after month 6. Once prescribed, all medication was prescribed to be taken 7 days a week except for in the drug holiday weight recovery arm.

Outcome measures

Measure	Behavior Therapy n=34 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=122 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Medication Adherence	68.1 % of days dose taken as prescribed	71.1 % of days dose taken as prescribed	—

SECONDARY outcome

Timeframe: months 0 through 30

Population: those with at least one follow up assessment. The second randomization arms are not included as all participants in those arms are derived from these two groups and this assessment period includes the entire duration of the second randomization. Also, the second randomization addressees weight gain, not ADHD treatment.

Raw number of behavior therapy sessions attended; participants could cross over to other treatment arm if moderately impaired after 6 months in initial randomly assigned arm

Outcome measures

Measure	Behavior Therapy n=50 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=174 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Number of Behavior Therapy Sessions	8.1 sessions attended Standard Deviation 10.5	8.1 sessions attended Standard Deviation 7.3	—

SECONDARY outcome

Timeframe: between 1 month and 24 months

Population: all participants prescribed an ER stimulant who were also went through the second randomization to one of three weight recovery interventions. One monitoring participant never prescribed med was excluded.First randomization arms not included as not all of those participants had a second randomization as it was adaptively based on change in zBMI.

difference in height z score from entry into weight recovery phase to exit from weight recovery phase (exact duration varied by participant). Randomization could not occur before month 6 (equaling a 24 month duration) but could start as late as month 29 (equaling a 1 month duration) of treatment based on the pattern of zBMI change by the individual participant.

Z scores used to account for differences in age and gender. More negative values reflecting less incremental height gain.

Outcome measures

Measure	Behavior Therapy n=24 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=23 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring n=23 Participants Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change in Height z Score During Weight Recovery Phase (Second Randomization)	-0.185 Z score Standard Deviation 0.232	-0.030 Z score Standard Deviation .247	-0.168 Z score Standard Deviation 0.337

SECONDARY outcome

Timeframe: 1 to 24 months duration

Population: all participants prescribed an ER stimulant who were also went through the second randomization to one of three weight recovery interventions.First randomization arms not included as not all of those participants had a second randomization as it was adaptively based on change in zBMI.

difference in weight z score from entry into weight recovery phase to exit from weight recovery phase (exact duration varied by participant). Randomization could not occur before month 6 (equaling a 24 month duration) but could start as late as month 29 (equaling a 1 month duration) of treatment based on the pattern of zBMI change by the individual participant.

Z scores used to account for differences in age and gender. Larger values reflect a greater incremental weight gain.

Outcome measures

Measure	Behavior Therapy n=24 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=23 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring n=23 Participants Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change in Weight z Score During Weight Recovery Phase (Second Randomization)	0.050 Z score Standard Deviation .289	0.262 Z score Standard Deviation 0.353	0.062 Z score Standard Deviation 0.331

SECONDARY outcome

Timeframe: between 1 month and 24 months

Population: all participants prescribed an ER stimulant who were also went through the second randomization to one of three weight recovery interventions. First randomization arms not included as not all of those participants had a second randomization as it was adaptively based on change in zBMI.

difference in BMI z score from entry into weight recovery phase to exit from weight recovery phase (exact duration varied by participant). Randomization could not occur before month 6 (equaling a 24 month duration) but could start as late as month 29 (equaling a 1 month duration) of treatment based on the pattern of zBMI change by the individual participant.

Z scores used to account for differences in age and gender. Larger values reflecting a greater incremental BMI gain.

Outcome measures

Measure	Behavior Therapy n=24 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=23 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring n=23 Participants Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change in Zscore for BMI During Weight Recovery Phase (Second Randomization)	0.243 Z score Standard Deviation 0.499	0.443 Z score Standard Deviation 0.459	0.247 Z score Standard Deviation 0.379

POST_HOC outcome

Timeframe: baseline to month 30 or last assessment point

Population: Includes all participants with at least one year of growth data as goal was to assess impact of extended treatment on growth. These same outcomes are reported elsewhere for the first randomization arms of Behavior Therapy and Med as well as the second randomization arms of cal supplement, drug holiday and monitoring (see outcomes 1 and 10).

measures change in height z score from baseline to last assessment with participants grouped based on actual medication usage versus randomly assigned group since participants were allowed to cross treatment arms after 6 months and not all participants assigned to medication used it consistently. The rarely med group (n=44) used med <12.5% of the study duration (with most using not at all). The consistent med group (N=38 used) med for at least 87.5% of their time in the study with most using the entire time. The inconsistent med group (N=111), used medication between 12.5 to 87.5 of the time (mean time on med was 45% of the time in the study) The other 37 participants did not have one year of growth data so were excluded from this analysis. Z scores used to account for differences in age and gender between groups. More negative values reflecting a smaller incremental height gain.

Outcome measures

Measure	Behavior Therapy n=38 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=111 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring n=44 Participants Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change in Height z Score by Actual Medication Usage	-0.248 Z score Standard Deviation .341	-0.113 Z score Standard Deviation .430	0.042 Z score Standard Deviation .464

POST_HOC outcome

Timeframe: baseline to month 30 or last assessment point

Population: Includes all participants with at least one year of growth data as goal was to assess impact of extended treatment on growth. These same outcomes are reported elsewhere for the first randomization arms of Behavior Therapy and Med as well as the second randomization arms of cal supplement, drug holiday and monitoring (see outcomes 2 and 11).

measures change in weight z score from baseline to last assessment with participants grouped based on actual medication usage versus randomly assigned group since participants were allowed to cross treatment arms after 6 months and not all participants assigned to medication used it consistently. The rarely med group (n=44) used med <12.5% of the study duration (with most using not at all). The consistent med group (N=38 used med for at least 87.5% of their time in the study with most using the entire time). The inconsistent med group (N=111, 27.5% used medication 45% of the time in the study. The other 37 participants did not have one year of growth data so were excluded from this analysis. Z scores used to account for differences in age and gender between groups. Higher values represent a greater incremental weight gain.

Outcome measures

Measure	Behavior Therapy n=38 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=111 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring n=44 Participants Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change in Weight z Score by Actual Medication Usage	-0.507 Z score Standard Deviation .335	-0.177 Z score Standard Deviation .443	0.112 Z score Standard Deviation .518

POST_HOC outcome

Timeframe: baseline to month 30 or last assessment point

Population: Includes all participants with at least one year of growth data as goal was to assess impact of extended treatment on growth. These same outcomes are reported elsewhere for the first randomization arms of Behavior Therapy and Med as well as the second randomization arms of cal supplement, drug holiday and monitoring (see outcomes 3 and 12).

measures change in BMI z score from baseline to last assessment with participants grouped based on actual medication usage versus randomly assigned group since participants were allowed to cross treatment arms after 6 months and not all participants assigned to medication used it consistently. The rarely med group (n=44) used med <12.5% of the study duration (with most using not at all). The consistent med group (N=38 used med for at least 87.5% of their time in the study with most using the entire time). The inconsistent med group (N=111, 27.5% used medication 45% of the time in the study. The other 37 participants did not have one year of growth data so were excluded from this analysis. Z scores used to account for differences in age and gender between groups. Higher values represent a larger BMI

Outcome measures

Measure	Behavior Therapy n=38 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=111 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring n=44 Participants Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change in BMI z Score by Actual Medication Usage	-0.554 Z score Standard Deviation .412	-0.170 Z score Standard Deviation .486	0.036 Z score Standard Deviation .528

POST_HOC outcome

Timeframe: between 1 month and 24 months

Population: all participants using an ER stimulant and were also assigned to a weight recovery arm. Arms from first randomization are not included as not all of those participants progressed to the second randomization which was done adaptively based on change in zBMI. Those arms are reported on for outcome 13.

difference in height z score from entry into weight recovery phase to exit from that phase (exact duration varied by participant). Randomization could not occur before month 6 (so max of 24 month duration) but could start as late as month 29 (equaling a 1 month duration) based on the pattern of zBMI change. In this post hoc analysis we grouped participants by what they did (caloric supplementation, drug holiday or monitoring) not what they were randomly assigned to. The most common change was from drug holiday to monitoring for participants who were not using medication on weekends before assignment to drug holiday (family stopped weekend med by own accord prior to 2nd randomization) so assignment to drug holiday did not alter actual frequency of use as was designed to.Therefore they were reclassified as monitoring as frequency of med use did not change.

Z score used to account for differences in age and gender between groups. Larger values reflect greater height change.

Outcome measures

Measure	Behavior Therapy n=23 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=16 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring n=31 Participants Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Difference in Height z Score During Weight Recovery Phase (Second Randomization) by Actual Usage	-0.184 Z score Standard Deviation 0.238	-0.095 Z score Standard Deviation 0.277	-0.105 Z score Standard Deviation 0.311

POST_HOC outcome

Timeframe: between 1 month and 24 months

Population: participants using an ER stimualnt and also randomized to one of the weight recovery treatments. Arms from first randomization are not included as not all of those participants progressed to the second randomization which was done adaptively based on change in zBMI. Those arms are reported on for outcome 14.

difference in height z score from entry into weight recovery phase to exit from that phase (exact duration varied by participant). Randomization could not occur before month 6 (so max of 24 month duration) but could start as late as month 29 (equaling a 1 month duration) based on the pattern of zBMI change. In this post hoc analysis we grouped participants by what they did (caloric supplementation, drug holiday or monitoring) not what they were randomly assigned to. The most common change was from drug holiday to monitoring for participants who were not using medication on weekends before assignment to drug holiday (family stopped weekend med by own accord prior to 2nd randomization) so assignment to drug holiday did not alter actual frequency of use as was designed to.Therefore they were reclassified as monitoring as frequency of med use did not change.

Z score used to account for differences in age and gender between groups. Higher values reflect greater incremental weight gain.

Outcome measures

Measure	Behavior Therapy n=23 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=16 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring n=31 Participants Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change in Weight z Score During Weight Recovery Phase (Second Randomization) Based on Actual Usage	0.055 zscore Standard Deviation 0.295	0.299 zscore Standard Deviation 0.452	0.084 zscore Standard Deviation 0.265

POST_HOC outcome

Timeframe: between 1 month and 24 months

Population: all participants prescribed an ER stimulant and also assigned to one of the weight recovery treatments. Arms from first randomization are not included as not all of those participants progressed to the second randomization which was done adaptively based on change in zBMI. Those arms are reported on for outcome 15.

difference in height z score from entry into weight recovery phase to exit from that phase (exact duration varied by participant). Randomization could not occur before month 6 (so max of 24 month duration) but could start as late as month 29 (equaling a 1 month duration) based on the pattern of zBMI change. In this post hoc analysis we grouped participants by what they did (caloric supplementation, drug holiday or monitoring) not what they were randomly assigned to. The most common change was from drug holiday to monitoring for participants who were not using medication on weekends before assignment to drug holiday (family stopped weekend med by own accord prior to 2nd randomization) so assignment to drug holiday did not alter actual frequency of use as was designed to.Therefore they were reclassified as monitoring as frequency of med use did not change.

Z score used to account for differences in age and gender between groups. Higher values reflect greater incremental BMI increase.

Outcome measures

Measure	Behavior Therapy n=23 Participants 10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject behavioral therapy: combination of individual and group parent training plus school consultation medication usage allowed after month 6 if still moderately impaired or worse on Clinical Global Impressions	ER Stimulant n=16 Participants daily use of 12 hour extended release methylphenidate product 12 hour methylphenidate product: medication to be taken daily for duration of study unless assigned to weight promotion arm	Monitoring n=31 Participants Subjects in either the behavior therapy arm or the medication arm who met criteria for weight recovery were randomly assigned to 1 of 3 weight recovery treatments. This arm consisted of monthly weight checks and continuation of daily extended release stimulant.
Change in BMI z Score During Weight Recovery Period (Second Randomization) Based on Actual Usage	0.248 Z score Standard Deviation 0.508	0.496 Z score Standard Deviation 0.576	0.260 Z score Standard Deviation .302

Adverse Events

Behavior Therapy

Serious events: 2 serious events

Other events: 33 other events

Deaths: 0 deaths

ER Stimulant

Serious events: 3 serious events

Other events: 156 other events

Deaths: 0 deaths

Dose Optimzed

Serious events: 4 serious events

Other events: 125 other events

Deaths: 0 deaths

Serious adverse events

Measure	Behavior Therapy n=41 participants at risk Participants completing a baseline assessment and at least one post baseline assessment of adverse events and were initially assigned to behavior arm which included a basic parenting intervention, additional advanced 8 week parent training intervention, monthly boosters, option for individual parent training sessions, and a school consultant assigned to each subject. Medication usage allowed after month 6 if at least moderately impaired includes all participants with at least one post baseline assessment of adverse events	ER Stimulant n=171 participants at risk Participants completing a baseline assessment and at least one post baseline assessment of adverse events who were initially assigned to daily use of extended release CNS Stimulant All study medication was prescribed to be taken daily for duration of study unless assigned to weight promotion drug holiday arm includes all participants with at least one post baseline assessment of adverse events	Dose Optimzed n=136 participants at risk This arm includes the 142 participants that had their dose of study medication systematically optimized through assessment of efficacy and tolerability at home and school. There participants could have come from either of the other two arms- initially assigned to either med or behavior. We added this post hoc arm as a subset of participants randomized to med never used med and a subset of behavior randomized participants did use medication. This group reports adverse event rates only in participants who used med for a sufficient duration to have their dose optimized.
Psychiatric disorders self injurious behavior	2.4% 1/41 • Number of events 1 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	0.00% 0/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	0.74% 1/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Psychiatric disorders aggression	2.4% 1/41 • Number of events 1 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	0.00% 0/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	0.00% 0/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Gastrointestinal disorders appendicitis	0.00% 0/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	0.58% 1/171 • Number of events 1 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	0.74% 1/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Gastrointestinal disorders abdominal pain	0.00% 0/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	0.58% 1/171 • Number of events 1 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	0.74% 1/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Respiratory, thoracic and mediastinal disorders shortness of breath	0.00% 0/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	0.58% 1/171 • Number of events 1 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	0.74% 1/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.

Other adverse events

Measure	Behavior Therapy n=41 participants at risk Participants completing a baseline assessment and at least one post baseline assessment of adverse events and were initially assigned to behavior arm which included a basic parenting intervention, additional advanced 8 week parent training intervention, monthly boosters, option for individual parent training sessions, and a school consultant assigned to each subject. Medication usage allowed after month 6 if at least moderately impaired includes all participants with at least one post baseline assessment of adverse events	ER Stimulant n=171 participants at risk Participants completing a baseline assessment and at least one post baseline assessment of adverse events who were initially assigned to daily use of extended release CNS Stimulant All study medication was prescribed to be taken daily for duration of study unless assigned to weight promotion drug holiday arm includes all participants with at least one post baseline assessment of adverse events	Dose Optimzed n=136 participants at risk This arm includes the 142 participants that had their dose of study medication systematically optimized through assessment of efficacy and tolerability at home and school. There participants could have come from either of the other two arms- initially assigned to either med or behavior. We added this post hoc arm as a subset of participants randomized to med never used med and a subset of behavior randomized participants did use medication. This group reports adverse event rates only in participants who used med for a sufficient duration to have their dose optimized.
Skin and subcutaneous tissue disorders skin picking	48.8% 20/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	47.4% 81/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	41.9% 57/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Nervous system disorders buccal movements	24.4% 10/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	17.0% 29/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	14.7% 20/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Psychiatric disorders anxiety	58.5% 24/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	60.8% 104/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	47.8% 65/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
General disorders dull, listless	24.4% 10/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	29.8% 51/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	26.5% 36/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Psychiatric disorders headache	29.3% 12/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	26.3% 45/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	29.4% 40/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Gastrointestinal disorders stomachache	26.8% 11/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	30.4% 52/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	31.6% 43/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Psychiatric disorders irritability	34.1% 14/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	46.8% 80/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	48.5% 66/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Psychiatric disorders depressed mood	22.0% 9/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	32.2% 55/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	35.3% 48/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Psychiatric disorders socially withdrawn	22.0% 9/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	20.5% 35/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	19.9% 27/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
General disorders loss of appetite	39.0% 16/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	49.7% 85/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	62.5% 85/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
General disorders trouble sleeping	26.8% 11/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	43.3% 74/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	41.2% 56/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.
Nervous system disorders motor/verbal tics	19.5% 8/41 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	17.5% 30/171 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.	18.4% 25/136 • up to 30 months (max study duration). Population is all participants with at least a baseline side effect rating and at least one additional rating of adverse events post baseline which is 212 cases total. This differs from other enrollment numbers as not all participants assigned to each group completed side effect assessments. We did not want to include missing cases as negative cases (no side effects) as that would impact side effect rates.

Additional Information

James Waxmonsky MD

Penn State College of Medicine

Phone: 7175318646

Email: jwaxmonsky@pennstatehealth.psu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place