Trial Outcomes & Findings for Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder (NCT NCT01972074)

NCT ID: NCT01972074

Last Updated: 2024-07-01

Results Overview

Treatment responders are defined as having a 25% reduction, from baseline to endpoint, in Social Responsiveness Scale, Second Edition: School-Age, Parent Report (SRS-2) total raw score and an Autism Spectrum Disorder Clinical Global Impression-Improvement (ASD CGI-I) score ≤2. The Social Responsiveness Scale, Second Edition (SRS-2) is a 65-item rating scale completed by the parents/guardians of children ages 4-18. It is used to measure the severity of autism spectrum disorder symptoms. Each item is rated on a 4-point Likert scale, ranging from 1=Not True to 4=Almost Always True. Higher scores indicate a higher severity of autism spectrum disorder symptoms. The Autism Spectrum Disorder Clinical Global Impression-Improvement subscale (ASD CGI-I) is a clinician-rated measure of the improvement of autism spectrum disorder symptoms. The subscale is rated on a 7-point Likert scale, ranging from 1=Very Much Improved to 7=Very Much Worse. Higher scores indicate less symptom improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 84 participants
• Primary outcome timeframe: 12 Weeks (from Baseline [Week 0] to Endpoint [Week 12])
• Results posted on: 2024-07-01

Participant Flow

Participants were recruited for 3 years (2015 - 2018). They were recruited from existing and new patients at 3 Massachusetts General Hospital sites: Bressler Program for Autism Spectrum Disorder, Lurie Center for Autism, and Child and Adolescent Outpatient Psychiatry Clinic. Participants were also recruited using flyers and internet advertisements.

Per protocol, participants were enrolled when they provided informed consent. They then underwent screening procedures to confirm eligibility. If eligible and willing/able to participate, participants then began study procedures. Some participants dropped out prior to starting study procedures and were, therefore, excluded from this analysis.

Participant milestones

Measure	Memantine Participants in the memantine arm will receive memantine in capsule form twice daily. It will be administered twice daily for 12 weeks (including a 4-week titration phase to a maximum dose of 20 mg per day). Participants will undergo neuroimaging before and after the 12-week treatment phase. Memantine: Capsule	Placebo Participants in the placebo arm will receive placebo (no active ingredients) in capsule form twice daily. It will be administered twice daily for 12 weeks. Participants will undergo neuroimaging before and after the 12-week treatment phase. Placebo: Capsule	Control Group Healthy controls will undergo neuroimaging twice (12 weeks apart) and will receive no intervention during the 12-week window.
Overall Study STARTED	22	21	18
Overall Study COMPLETED	16	17	15
Overall Study NOT COMPLETED	6	4	3

Reasons for withdrawal

Measure	Memantine Participants in the memantine arm will receive memantine in capsule form twice daily. It will be administered twice daily for 12 weeks (including a 4-week titration phase to a maximum dose of 20 mg per day). Participants will undergo neuroimaging before and after the 12-week treatment phase. Memantine: Capsule	Placebo Participants in the placebo arm will receive placebo (no active ingredients) in capsule form twice daily. It will be administered twice daily for 12 weeks. Participants will undergo neuroimaging before and after the 12-week treatment phase. Placebo: Capsule	Control Group Healthy controls will undergo neuroimaging twice (12 weeks apart) and will receive no intervention during the 12-week window.
Overall Study Adverse Event	4	1	0
Overall Study Lack of Efficacy	1	1	0
Overall Study Lost to Follow-up	0	1	1
Overall Study Withdrawal by Subject	1	1	1
Overall Study Scanner Unavailable	0	0	1

Baseline Characteristics

Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder

Baseline characteristics by cohort

Measure	Memantine n=22 Participants Participants in the memantine arm will receive memantine in capsule form twice daily. It will be administered twice daily for 12 weeks (including a 4-week titration phase to a maximum dose of 20 mg per day). Participants will undergo neuroimaging before and after the 12-week treatment phase. Memantine: Capsule	Placebo n=21 Participants Participants in the placebo arm will receive placebo (no active ingredients) in capsule form twice daily. It will be administered twice daily for 12 weeks. Participants will undergo neuroimaging before and after the 12-week treatment phase. Placebo: Capsule	Control Group n=18 Participants Healthy controls will undergo neuroimaging twice (12 weeks apart) and will receive no intervention during the 12-week window.	Total n=61 Participants Total of all reporting groups
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Region of Enrollment United States	22 participants n=93 Participants	21 participants n=4 Participants	18 participants n=27 Participants	61 participants n=483 Participants
Age, Categorical <=18 years	22 Participants n=93 Participants	21 Participants n=4 Participants	18 Participants n=27 Participants	61 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Continuous	13.2 years STANDARD_DEVIATION 2.7 • n=93 Participants	13.3 years STANDARD_DEVIATION 2.5 • n=4 Participants	12.6 years STANDARD_DEVIATION 2.7 • n=27 Participants	13.0 years STANDARD_DEVIATION 2.6 • n=483 Participants
Sex: Female, Male Female	5 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants	16 Participants n=483 Participants
Sex: Female, Male Male	17 Participants n=93 Participants	16 Participants n=4 Participants	12 Participants n=27 Participants	45 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	3 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=93 Participants	20 Participants n=4 Participants	17 Participants n=27 Participants	58 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	2 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) White	20 Participants n=93 Participants	20 Participants n=4 Participants	15 Participants n=27 Participants	55 Participants n=483 Participants
Race (NIH/OMB) More than one race	2 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	4 Participants n=483 Participants

PRIMARY outcome

Timeframe: 12 Weeks (from Baseline [Week 0] to Endpoint [Week 12])

Population: Participants included in this analysis were exposed to study medication for at least 2 weeks. Participants in the Control Group were excluded from this analysis because they did not receive study medication and, therefore, cannot be categorized into Treatment Responders vs. Treatment Non-Responders.

Treatment responders are defined as having a 25% reduction, from baseline to endpoint, in Social Responsiveness Scale, Second Edition: School-Age, Parent Report (SRS-2) total raw score and an Autism Spectrum Disorder Clinical Global Impression-Improvement (ASD CGI-I) score ≤2. The Social Responsiveness Scale, Second Edition (SRS-2) is a 65-item rating scale completed by the parents/guardians of children ages 4-18. It is used to measure the severity of autism spectrum disorder symptoms. Each item is rated on a 4-point Likert scale, ranging from 1=Not True to 4=Almost Always True. Higher scores indicate a higher severity of autism spectrum disorder symptoms. The Autism Spectrum Disorder Clinical Global Impression-Improvement subscale (ASD CGI-I) is a clinician-rated measure of the improvement of autism spectrum disorder symptoms. The subscale is rated on a 7-point Likert scale, ranging from 1=Very Much Improved to 7=Very Much Worse. Higher scores indicate less symptom improvement.

Outcome measures

Measure	Memantine n=19 Participants Participants in the memantine arm will receive memantine in capsule form twice daily. It will be administered twice daily for 12 weeks (including a 4-week titration phase to a maximum dose of 20 mg per day). Participants will undergo neuroimaging before and after the 12-week treatment phase. Memantine: Capsule	Placebo n=21 Participants Participants in the placebo arm will receive placebo (no active ingredients) in capsule form twice daily. It will be administered twice daily for 12 weeks. Participants will undergo neuroimaging before and after the 12-week treatment phase. Placebo: Capsule
Treatment Responder	9 Participants	4 Participants

Adverse Events

Memantine

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Control Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Memantine n=22 participants at risk Participants in the memantine arm will receive memantine in capsule form twice daily. It will be administered twice daily for 12 weeks (including a 4-week titration phase to a maximum dose of 20 mg per day). Participants will undergo neuroimaging before and after the 12-week treatment phase. Memantine: Capsule	Placebo n=21 participants at risk Participants in the placebo arm will receive placebo (no active ingredients) in capsule form twice daily. It will be administered twice daily for 12 weeks. Participants will undergo neuroimaging before and after the 12-week treatment phase. Placebo: Capsule	Control Group Healthy controls will undergo neuroimaging twice (12 weeks apart) and will receive no intervention during the 12-week window.
Gastrointestinal disorders Abdominal Discomfort	9.1% 2/22 • Number of events 2 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	4.8% 1/21 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Psychiatric disorders Anxious/Worried	9.1% 2/22 • Number of events 2 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	9.5% 2/21 • Number of events 2 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Respiratory, thoracic and mediastinal disorders Cold/Infection/Allergy	13.6% 3/22 • Number of events 3 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	4.8% 1/21 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Gastrointestinal disorders Constipation	0.00% 0/22 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	4.8% 1/21 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Metabolism and nutrition disorders Decreased Appetite	9.1% 2/22 • Number of events 2 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	0.00% 0/21 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Gastrointestinal disorders Diarrhea	4.5% 1/22 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	0.00% 0/21 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Nervous system disorders Dizzy/Lightheaded	4.5% 1/22 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	4.8% 1/21 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Nervous system disorders Fatigue	9.1% 2/22 • Number of events 2 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	9.5% 2/21 • Number of events 2 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Nervous system disorders Headache	18.2% 4/22 • Number of events 5 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	9.5% 2/21 • Number of events 2 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Metabolism and nutrition disorders Increased Appetite	13.6% 3/22 • Number of events 3 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	0.00% 0/21 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Renal and urinary disorders Increased Bed Wetting	4.5% 1/22 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	0.00% 0/21 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Nervous system disorders Insomnia	13.6% 3/22 • Number of events 3 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	9.5% 2/21 • Number of events 2 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Psychiatric disorders Irritability	0.00% 0/22 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	14.3% 3/21 • Number of events 3 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Psychiatric disorders Irritability & Agitation	4.5% 1/22 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	4.8% 1/21 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/22 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	4.8% 1/21 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Skin and subcutaneous tissue disorders Rash	0.00% 0/22 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	4.8% 1/21 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Nervous system disorders Sedation	9.1% 2/22 • Number of events 2 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	4.8% 1/21 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Psychiatric disorders Self-Harm	4.5% 1/22 • Number of events 1 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	0.00% 0/21 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.
Psychiatric disorders Suicidal Ideation	9.1% 2/22 • Number of events 2 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	0.00% 0/21 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.	— 0/0 • 12 Weeks Adverse events were collected from participants in the memantine arm and the placebo arm systematically, via regular investigator assessment. At every study visit, study clinicians queried participants and their parent(s)/guardian(s) about any adverse events that may have occurred since the last study visit. Participants in the Control Group were excluded from this analysis because they did not receive study medication and adverse events were not monitored/assessed for the Control Group.

Additional Information

Gagan Joshi, MD

Massachusetts General Hospital

Phone: (617) 724-1541

Email: joshi.gagan@mgh.harvard.edu

Results disclosure agreements

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