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Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Massachusetts General Hospital
Sponsor:
Collaborator:
Mclean Hospital
Information provided by (Responsible Party):
Gagan Joshi, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01972074
First received: October 24, 2013
Last updated: November 24, 2014
Last verified: November 2014
  Purpose

This study is a 12-week randomized-controlled trial of memantine hydrochloride (Namenda) for the treatment for social impairment in adolescents with autism spectrum disorder (ASD). The investigators will also conduct pre- and post-treatment neuroimaging (fMRI and HMRS) to assess neural functional deficits in adolescents with ASD compared to healthy volunteer adolescents and to assess any effects of memantine therapy on neural function in adolescents with ASD. The investigators hypothesize that short-term memantine monotherapy will be safe, well-tolerated, and effective in improving the core symptoms of autism spectrum disorder in adolescents with ASD. Additionally, the investigators hypothesize that following memantine therapy, ASD subjects will exhibit a decrease in glutamate (Glu) concentration in the anterior-cingulate cortex (ACC) and a change towards normalization in altered functional connectivity of the ACC and medial temporal lobes, consistent with improvement in social impairments in ASD. The investigators hypothesize that compared to healthy volunteer subjects, ASD subjects will significantly differ on neuroimaging measures at baseline but that following memantine therapy, the difference between ASD and healthy volunteer neuroimaging data will decrease.


Condition Intervention Phase
Autism Spectrum Disorder
Drug: Memantine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Social Responsiveness Scale-Second Edition (SRS-2) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    The Social Responsiveness Scale is a 65-item rating scale completed by the parent used to measure the severity of autism spectrum symptoms as they occur in natural settings

  • Clinical Global Impression-Improvement (CGI-I) subscale [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    The CGI-I is a measure of illness improvement.


Estimated Enrollment: 90
Study Start Date: November 2014
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Experimental: Memantine
Memantine administered in tablet form twice daily titrated to a maximum dose of 20 mg for 12 weeks
Drug: Memantine
Tablet
Other Name: Namenda
No Intervention: Control Group
Healthy volunteers will be scanned twice (12 weeks apart) and will receive no intervention.

  Eligibility

Ages Eligible for Study:   13 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria (all participants)

  1. Male & female subjects ages 13-17 years (inclusive).
  2. Tanner stage of ≥III (by Petersen Pubertal Development Scale66).

    Participants with ASD

  3. DSM-5 ASD diagnostic criteria as established by clinical diagnostic interview
  4. 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)71 and a score of ≥4 on the clinician-administered Clinical Global Impression-Severity scale (CGI-S).

Healthy Control Participants 3. Age-, sex-, & IQ-matched. 4. No Axis I diagnoses as established by the Kiddie Schedule for Affective Disorders and Schizophrenia—Epidemiological Version (K-SADS-E)70 & confirmed by clinical diagnostic interview.

5. No significant traits of ASD as screened by SRS-2 (raw score <60).

Exclusion Criteria (all participants)

  1. IQ ≤85 based on the Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary and Matrix Reasoning subtests
  2. Impaired communicative speech
  3. Subjects currently treated with the following medications (known to impact glutamate levels):

    1. Mood stabilizers: Lamotrigine, topiramate, valproate
    2. SGAs: Risperidone, aripiprazole, quetiapine, paliperidone, asenapine
    3. FGAs: Clozapine, haloperidol
    4. SSRIs: Citalopram, sertraline
    5. MAOIs (all)
    6. Amantadine
    7. N-acetylcysteine
    8. D-cycloserine
    9. Lithium
    10. Methylphenidate
    11. Nortriptyline
    12. Riluzole
    13. Ketamine
    14. Acamprosate
    15. Glycine
    16. Antibiotics: Ampicillin, riluzole, minocycline, ceftriaxonze
  4. 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.
  5. Contraindications to MR scanning (claustrophobia, braces, metal in the body, etc.)
  6. Subjects who are pregnant and/or nursing.
  7. Subjects with a history of non-febrile seizures without a clear and resolved etiology.
  8. Subjects with a history of or a current liver or kidney disease.
  9. Clinically unstable psychiatric conditions or judged to be at serious suicidal risk.
  10. History of substance use (except nicotine or caffeine) within past 3 months
  11. Serious, stable or unstable systemic illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
  12. Subjects with severe hepatic impairment (LFTs > 3 times ULN).
  13. Subjects with genitourinary conditions that raise urine pH (e.g., renal tubular acidosis, severe infection of the urinary tract).
  14. Known hypersensitivity to memantine.
  15. Severe allergies or multiple adverse drug reactions.
  16. A non-responder or history of intolerance to memantine, after treatment at adequate doses as determined by the clinician.
  17. Investigator and his/her immediate family defined as the investigator's spouse, parent, child, grandparent, or grandchild.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01972074

Contacts
Contact: Stephannie Furtak, BA 617-724-2344 sfurtak1@partners.org
Contact: Leah Feinberg, BS 617-726-4651 lkfeinberg@mgh.harvard.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Stephannie Furtak, BA    617-724-2344    Sfurtak1@partners.org   
Contact: Leah Feinberg, BS    617-726-4651    lkfeinberg@mgh.harvard.edu   
Principal Investigator: Gagan Joshi, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Mclean Hospital
Investigators
Principal Investigator: Gagan Joshi, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Gagan Joshi, MD, Associate Professor of Psychiatry, Harvard Medical School; Director, Bressler Program for Autism Spectrum Disorders, Pediatric Psychopharmacology, Massachusetts General Hospital, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01972074     History of Changes
Other Study ID Numbers: 2013-P-001826
Study First Received: October 24, 2013
Last Updated: November 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Autism spectrum disorder
Treatment
Adolescents
Memantine
functional Magnetic Resonance Imaging
MRS
Neuroimaging

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

ClinicalTrials.gov processed this record on November 25, 2014