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

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

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.

Study Overview

• Status: Terminated
• Conditions: Autism Spectrum Disorder; Autism; Nonverbal Learning Disability
• Intervention / Treatment: Drug: Memantine Hydrochloride; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Memantine; Memantine administered in tablet form twice daily titrated to a maximum dose of 20 mg for 12 weeks.	Drug: Memantine Hydrochloride; 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).
Placebo Comparator: Placebo; 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; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Gagan Joshi, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Brignell A, Marraffa C, Williams K, May T. Memantine for autism spectrum disorder. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013845. doi: 10.1002/14651858.CD013845.pub2.
• Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2018
• Primary Completion (Actual): November 25, 2025
• Study Completion (Actual): November 25, 2025

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 12, 2018

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Autism; Massachusetts General Hospital
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder; non-verbal learning disabilities; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Adamantane; Bridged-Ring Compounds; Amantadine; Memantine
• Other Study ID Numbers: 2018P001082

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No