A Trial of Memantine Versus Placebo in Children With Autism

This study is currently recruiting participants.
Verified January 2014 by Anagnostou, Evdokia, M.D.
Sponsor:
Collaborators:
Mount Sinai School of Medicine
Rush University Medical Center
Nationwide Children's Hospital
Ohio State University
Information provided by (Responsible Party):
Evdokia Anagnostou, Anagnostou, Evdokia, M.D.
ClinicalTrials.gov Identifier:
NCT01372449
First received: June 2, 2011
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Autism Spectrum Disorder
Drug: Memantine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-site Double-blind Placebo-controlled Trial of Memantine Versus Placebo in Children With Autism Targeting Memory and Motor Planning

Resource links provided by NLM:


Further study details as provided by Anagnostou, Evdokia, M.D.:

Primary Outcome Measures:
  • NEPSY apraxia and repetition of nonsense words subtests [ Time Frame: Baseline, Week 12, Week 24 (Measuring change from Baseline, middle of trial and end of trial) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Vineland Adaptive Behavior Scale - Revised [ Time Frame: Baseline, Week 12, Week 24 (Measuring change from Baseline, middle of trial and end of trial) ] [ Designated as safety issue: No ]
    Outcome Measure is going to report a change. The Vineland Scale is a semi-structured informant interview that assesses subjects' daily functioning. It is typically administered to a caretaker/family member. This scale has been found to assess social deficits in autism and relative strengths in daily living skills.

  • Safety Monitoring Uniform Research Form [ Time Frame: Screening, Baseline, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 16, Week 20, Week 24 ] [ Designated as safety issue: Yes ]
    The SMURF consists of three parts. Part 1 contains a "General Inquiry" to obtain all information about possible physical complaints, using general probes. Part 2 comprises "Specific Inquiries" about physical complaints, organized roughly around different body systems. Part 3 concludes with a "Closing Inquiry" in which the clinician can ask about any physical or other problems he/she has pre-existing knowledge about or which he/she noticed during the rest of the inquiry.


Estimated Enrollment: 60
Study Start Date: December 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Memantine Drug: Memantine
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.
Other Name: Namenda
Placebo Comparator: Placebo

Detailed Description:

Abnormalities in the modulation of the glutamate system have been reported by multiple investigators studying animal models, post-mortem brains, and single gene disorders that have overlapping phenotypes with autism. Abnormalities in glutamatergic function have been reported in disorders affecting a variety of behavioral and neurological domains, from mood stability, to cognitive flexibility, memory, and motor function. Numerous studies have reported a variety of memory and motor deficits in children with autism. Whereas the neurobiology of such deficits is an area of active research, there is a paucity of intervention research for such deficits in autism. This study will attempt to study the effect of an NMDA inhibitor, memantine, on memory, and motor praxis/expressive language skills in children with autism.

Methods: Children ages 6-12 years who are verbal and meet criteria for Autism Spectrum Disorder will be recruited across 3 sites. After consent, the children will be assessed for memory function, expressive language output and motor skills/praxis. They will then be randomized 1:1 to memantine versus placebo for 6 months. The effects of this medication on the above mentioned symptoms domains as well as its safety in this population will be studied over the 6 month period.

  Eligibility

Ages Eligible for Study:   6 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Male or female outpatients 6 to 12 years of age
  2. Verbal (Module 2 or 3 on ADOS)
  3. Meet DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision) for Autism Spectrum Disorder. The diagnosis will be confirmed with Autism Diagnostic Interview-Revised (ADI-R) and ADOS Module 2 or 3.
  4. Parents report difficulties with motor skills
  5. Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Screening and Baseline
  6. 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
  7. 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
  8. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigators
  9. 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
  10. 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
  11. 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

Exclusion Criteria:

  1. Patients born prior to 35 weeks gestational age
  2. Patients with any primary psychiatric diagnosis other than autism at Screening: a history of ADHD, bipolar disorder, psychosis, post-traumatic stress disorder, schizophrenia, or major depressive disorder
  3. 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
  4. 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.
  5. Patients who plan to initiate or change pharmacological or nonpharmacologic interventions during the course of the study
  6. Patients on d-cycloserine or riluzole as they both target the glutamate system
  7. Patients on agents that alkalinize the urine (acetazolamide, potassium citrate, and sodium bicarbonate), as they decrease the elimination of memantine
  8. Patients who have received treatment with memantine
  9. Patients with a history of hypersensitivity reaction to dextromethorphan, amantadine, or any other NMDA receptor antagonists
  10. Have an Aberrant Behavior Checklist (ABC) Irritability subscale score > 16*
  11. Patients unable to tolerate venipuncture procedures for blood sampling
  12. Patients who, in the Investigator's opinion, might not be suitable for the study
  13. Children weighing under 20 kg (to meet FDA approvals)
  14. Patients with a positive pregnancy test
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01372449

Contacts
Contact: Dina Zaghloul, B.MSc 416-425-6220 ext 6602 dzaghloul@hollandbloorview.ca

Locations
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Natalie Forburger, MA    312-563-2272    natalie_m_forburger@rush.edu   
Contact: Sarah E Youngkin, MPH    312-942-5431    sarah_youngkin@rush.edu   
Principal Investigator: Latha V Soorya, PhD         
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Contact: Lauren Bush, BA    212-241-2826    lauren.a.bush@mssm.edu   
Principal Investigator: David Grodberg, MD         
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Melinda R Helton, RN    614-722-2607    melinda.helton@nationwidechildrens.org   
Contact: Christine Hapanowicz, CCRP    614-722-2605    christine.hapanowicz@nationwidechildrens.org   
Principal Investigator: Daniel L Coury, MD         
Sub-Investigator: Eric Butter, PhD         
Sponsors and Collaborators
Evdokia Anagnostou
Mount Sinai School of Medicine
Rush University Medical Center
Nationwide Children's Hospital
Ohio State University
Investigators
Study Chair: Evdokia Anagnostou, MD Holland Bloorview Kids Rehabilitation Hospital
Principal Investigator: Latha V Soorya, PhD Rush University Medical Center
Principal Investigator: David Grodberg, MD Mount Sinai School of Medicine
Principal Investigator: Daniel L Coury, MD Nationwide Children's Hospital
Principal Investigator: Eric Butter, PhD Nationwide Children's Hospital
Principal Investigator: Joel Bregman, MD The Center for Autism
  More Information

No publications provided

Responsible Party: Evdokia Anagnostou, Clinician Scientist, Anagnostou, Evdokia, M.D.
ClinicalTrials.gov Identifier: NCT01372449     History of Changes
Other Study ID Numbers: 111576
Study First Received: June 2, 2011
Last Updated: January 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Anagnostou, Evdokia, M.D.:
Autism
Psychopharmacology
Clinical Trial
Children

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Mental Disorders Diagnosed in Childhood
Mental Disorders
Memantine
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 14, 2014