A Multi-site Double-blind Placebo-controlled Trial of Memantine Versus Placebo in Children With Autism (MEM)

NCT01372449 | Completed Phase 2 DMC

• 1 other identifier: 111576
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

This study will attempt to study the effect of memantine, on memory, and motor praxis/expressive language skills in children with autism. The investigators will recruit children ages 6-12 years who are verbal and meet criteria for Autism Spectrum Disorder. The children will be assessed for memory function, expressive language output and motor skills/praxis. They will then be randomized to memantine or placebo for 6 months. The effects of this medication and its safety in this population will be studied over the 6 month period.

Conditions

Autism Spectrum Disorder

Keywords

Autism; Psychopharmacology; Clinical Trial; Children

Outcome Measures

Primary Outcomes (2)

• Developmental Neuropsychological Assessment (NEPSY) Apraxia and Repetition of Nonsense Words Subtests

  Outcome Measure is going to report a change. The NEPSY provides a developmental neuropsychological assessment for children age 3-12. It was designed to assess basic and complex aspects of cognitive capacities that are critical to children's ability to learn and be productive both in and out of school settings

  Baseline, Week 12, Week 24 (Measuring change from Baseline, middle of trial and end of trial)

• Expressive Vocabulary Test (EVT)

  Baseline, Week 12, Week 24 (Measuring change from Baseline, middle of trial and end of trial)

Secondary Outcomes (2)

• Vineland Adaptive Behavior Scale - Revised

  Baseline, Week 12, Week 24 (Measuring change from Baseline, middle of trial and end of trial)

• Safety Monitoring Uniform Research Form

  Screening, Baseline, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 16, Week 20, Week 24

Study Arms (2)

Memantine

ACTIVE COMPARATOR

Drug: Memantine

Placebo

PLACEBO COMPARATOR

Placebo Comparator

Drug: Placebo

Interventions

Memantine DRUG

Memantine will be initiated at 3 mg. The dose will be increased every week by 3 mg for a maximum of 12mg for subjects weighing ≥ 60kg, 9mg for subjects weighing ≥ 40 kg but \<60 kg, and 6 mg for subjects weighing ≥ 20 kg but \< 40kg.

Also known as: Namenda

Memantine

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female outpatients 6 to 12 years of age
• Verbal; Module 2 or 3 on Autism Diagnostic Observation Schedule (ADOS)
• Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) for Autism Spectrum Disorder. The diagnosis will be confirmed with Autism Diagnostic Interview-Revised (ADI-R) and ADOS Module 2 or 3.
• Parents report difficulties with motor skills
• Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Screening and Baseline
• If already receiving stable nonpharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening and will not electively initiate new or modify ongoing interventions for the duration of the study
• Participants can be on up to 2 concomitant psychotropic medications before entering the study, provided that they have been on a stable dose for 30 days and have no plans to adjust the dose for the duration of study
• Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigators
• Prior to the conduct of any study-specific procedures, the patient must provide assent to participate in the study (if developmentally appropriate), and the parent or legal guardian must provide written informed consent
• The patient and the patient's parent or legal guardian must be able to speak and understand English sufficiently to understand the nature of the study and to allow for the completion of all study assessments
• The parent or legal guardian must be capable of providing reliable information about the patient's condition, agree to oversee the administration of study drug, and accompany the patient to all clinic visits

You may not qualify if:

• Patients born prior to 35 weeks gestational age
• Patients with any primary psychiatric diagnosis other than autism at Screening: a history of Attention Deficit Hyperactivity Disorder (ADHD), bipolar disorder, psychosis, post-traumatic stress disorder, schizophrenia, or major depressive disorder
• Patients with a medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal MRI/structural lesion of the brain
• Patients with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease.
• Patients who plan to initiate or change pharmacological or nonpharmacologic interventions during the course of the study
• Patients on d-cycloserine or riluzole as they both target the glutamate system
• Patients on agents that alkalinize the urine (acetazolamide, potassium citrate, and sodium bicarbonate), as they decrease the elimination of memantine
• Patients who have received treatment with memantine in the past with no response
• Patients with a history of hypersensitivity reaction to dextromethorphan, amantadine, or any other NMDA receptor antagonists
• Patients unable to tolerate venipuncture procedures for blood sampling
• Patients who, in the Investigator's opinion, might not be suitable for the study
• Children weighing under 20 kg (to meet FDA approvals)
• Patients with a positive pregnancy test

Sponsors & Collaborators

• Evdokia Anagnostou: lead
• Icahn School of Medicine at Mount Sinai: collaborator
• Rush University Medical Center: collaborator
• Nationwide Children's Hospital: collaborator

Study Sites (2)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Related Publications (2)

• 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.

  PMID: 36006807 DERIVED

• Soorya LV, Fogg L, Ocampo E, Printen M, Youngkin S, Halpern D, Kolevzon A, Lee S, Grodberg D, Anagnostou E. Neurocognitive Outcomes from Memantine: A Pilot, Double-Blind, Placebo-Controlled Trial in Children with Autism Spectrum Disorder. J Child Adolesc Psychopharmacol. 2021 Sep;31(7):475-484. doi: 10.1089/cap.2021.0010.

  PMID: 34543081 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder

Interventions

Memantine

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Evdokia Anagnostou, M.D.

  Holland Bloorview Kids Rehabilitation Hospital

  STUDY CHAIR

• Latha V Soorya, Ph.D.

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

• David Grodberg, M.D.

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinician Scientist

Study Record Dates

• First Submitted: June 2, 2011
• First Posted: June 14, 2011
• Study Start: December 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: March 20, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)