Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions

Study Overview
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Brief Summary
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This study is a 12-week randomized-controlled trial of memantine hydrochloride (Namenda) for the treatment of social impairment in youth with Non-Verbal Learning Disorder, High-Functioning Autism Spectrum Disorder, and related conditions. Eligible participants will be males and females ages 8-18. This study consists of up to 6 visits to Massachusetts General Hospital.

Official Title
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Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions: A Randomized-controlled Trial

Conditions
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Autism, Autism Spectrum Disorder, Nonverbal Learning Disability

Intervention / Treatment
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* Drug: Memantine Hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male & female subjects ages 8-18 years (inclusive). Diagnostic Statistical Manual (DSM)-5 Autism Spectrum Disorder (ASD) diagnostic criteria as established by clinical diagnostic interview At least moderate severity of social impairment as measured by a total raw score of ≥85 on the parent/guardian-completed Social Responsiveness Scale-Second Edition (SRS-2)14 and a score of ≥4 on the clinician-administered Clinical Global Impression-Severity scale (CGI-S)17. Exclusion Criteria: IQ ≤70 based on the Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary and Matrix Reasoning subtests Impaired communicative speech Subjects currently treated with the following medications (known to impact glutamate levels): Lamotrigine, Amantadine, N-acetylcysteine, D-cycloserine Subjects treated with a psychotropic medication not listed above on a dose that has not been stable for at least 4 weeks prior to study baseline. Co-administration of drugs that compete with memantine for renal elimination using the same renal cationic system, including hydrochlorothiazide, triamterene, metformin, cimetidine, ranitidine, quinidine, and nicotine Initiation of a new psychosocial intervention within 30 days prior to randomization. Subjects who are pregnant and/or nursing. Subjects with a history of non-febrile seizures without a clear and resolved etiology. Subjects with a history of or a current liver or kidney disease. Clinically unstable psychiatric conditions or judged to be at serious suicidal risk. Subjects who meet on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-E) for alcohol or drug dependence or abuse. If the subject has a recent history of substance abuse, there will be a two-week washout period before initiating the trial as an added precaution. There are no known safety issues relating to memantine and recent history of substance abuse. Serious, stable or unstable systemic illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. Subjects with severe hepatic impairment (LFTs > 3 times ULN). Subjects with genitourinary conditions that raise urine pH (e.g., renal tubular acidosis, severe infection of the urinary tract). Known hypersensitivity to memantine. Severe allergies or multiple adverse drug reactions. A history of intolerance or adequate exposure to memantine, as determined by the clinician. Investigator and his/her immediate family defined as the investigator's spouse, parent, child, grandparent, or grandchild.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Memantine<br>Memantine administered in tablet form twice daily titrated to a maximum dose of 20 mg for 12 weeks. | Drug: Memantine Hydrochloride<br>* Participating children and adolescents with Non-Verbal Learning Disorder and related conditions (NVLD-RC) who meet the eligibility criteria will be randomly assigned to memantine for the course of the 12-week randomized controlled trial (RCT).<br>|
| Placebo Comparator: Placebo<br>Subjects in the placebo control group will receive a matched placebo pill with no active ingredients. This will be administered twice daily for 12 weeks. | Drug: Placebo<br>* Participating children and adolescents with Non-Verbal Learning Disorder and related conditions (NVLD-RC) who meet the eligibility criteria will be randomly assigned to placebo for the course of the 12-week randomized controlled trial (RCT).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression-Improvement Scale (CGI-I) | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale (1 to 7-- with higher numbers indicating more severely affected) that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism, Massachusetts General Hospital