A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders

The main objective of this study is to evaluate the safety and effectiveness of memantine (Namenda®) for cognitive and behavioral impairment in adults ages 18-50 years with autism spectrum disorders (ASD). This is an exploratory, 12-week, pilot study, seeking to determine whether Namenda is efficacious and well tolerated in the treatment of adults with ASD. The study results will be used to generate hypotheses for a larger randomized controlled clinical trial with explicit hypotheses and sufficient statistical power.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorders
• Intervention / Treatment: Drug: Memantine

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusions

• Male and female outpatients 18-50 years of age.
• Participants must have DSM-IV-TR diagnosis of PDD and displaying PDD symptoms with at least moderate impairment (SRS score ≥ 85 and CGI-PDD ≥ 4).
• Fulfills diagnosis of autism spectrum disorders by meeting DSM-IV-TR PDD diagnostic criteria of autistic disorder (with the exception of a total lack of spoken language), Asperger's disorder, or PDD-NOS as established by clinical interview and confirmed by DICA-R PDD module.
• Subjects and/or their legal representative must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol.
• Subjects and/or their legal representative must be considered reliable reporters.
• Each subject and/or their authorized legal representative must understand the nature of the study. The subject and/or their legal representative must sign an informed consent document.
• Subject must be able to participate in mandatory blood draws.
• Subject must be able to swallow pills.
• Subjects with mood, anxiety, or disruptive behavior disorders will be allowed to participate in the study provided they do not meet any exclusionary criteria.

Exclusions

• IQ < 85.
• Total lack of spoken language.
• DSM-IV-TR PDD diagnoses of Rett's disorder, or childhood disintegrative disorder.
• Clinically unstable psychiatric conditions or judged to be at serious suicidal risk.
• Active symptoms of anorexia or bulimia nervosa
• Current diagnosis of a psychotic disorder or unstable bipolar disorder.
• History of recent or current (past 30 days) clinically significant depressive or anxiety disorder that warrants treatment.
• Current diagnosis of schizophrenia.
• History of substance use (except nicotine or caffeine) within past 3 months
• 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) and those with severely impaired renal function (eGFR < 30).
• Subjects with genitourinary conditions that raise urine pH (e.g., renal tubular acidosis, severe infection of the urinary tract).
• Uncorrected hypothyroidism or hyperthyroidism.
• Subjects with untreated and/or unstable diabetes.
• Non-febrile seizures without a clear and resolved etiology.
• Pregnant or nursing females.
• Known hypersensitivity to memantine.
• Severe allergies or multiple adverse drug reactions.
• A non-responder or history of intolerance to memantine, after treatment at adequate doses 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Memantine (Namenda) Treatment

Drug: Memantine; Memantine (Namenda®) was approved by the U.S. Food and Drug Administration in 2003 and by the European Agency for the Evaluation of Medical Products in 2002 for the treatment of moderate to severe Alzheimer's disease. Evidence from available treatment trials of memantine in ASD and non-ASD populations of youth and adults strongly suggest that memantine could be an effective agent for the treatment of adults with ASD. During the 12 weeks of study duration, subjects will be evaluated at weekly intervals for the first 4 weeks and thereafter every 3 weeks. Memantine will be administered in divided dose twice a day in the morning and evening. Titration of study medication will be guided by a forced titration schedule with an option for slower titration or holding at lower dose per clinician judgment. Safety, effectiveness, response and side effects will be evaluated.; Other Names: Namenda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Reduction in ASD Symptom Severity as Defined by the Social Responsiveness Scale (SRS)	Number of participants with reduction in ASD symptom severity defined as a reduction in Social Responsiveness Scale (SRS) score from baseline of greater than or equal to 30%. The SRS is a 65-item rating scale completed by an informant to measure the severity of autism spectrum symptoms as they occur in natural settings.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Reduction in ASD Symptom Severity as Defined by the NIMH Clinical Global Impression for Pervasive Developmental Disorders (CGI-PDD) Improvement Score	Number of participants with reduction in ASD symptom severity defined as an NIMH Clinical Global Impression (CGI) Pervasive Developmental Disorder (PDD) Improvement score less than or equal to 2. The CGI-Improvement is a clinician-rated measure of improvement. Scores range from 1 (very much improved) to 7 (very much worse) for PDD.	Pre-treatment - 12 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: November 19, 2010
• First Submitted That Met QC Criteria: April 11, 2011
• First Posted (Estimate): April 12, 2011

Study Record Updates

• Last Update Posted (Estimate): March 24, 2016
• Last Update Submitted That Met QC Criteria: February 26, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Adults; Autism Spectrum Disorders; Memantine; Namenda; Pervasive Developmental Disorders
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurodevelopmental Disorders; Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: 2010-P-000016