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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01972074
Recruitment Status : Completed
First Posted : October 30, 2013
Last Update Posted : October 19, 2018
Mclean Hospital
Information provided by (Responsible Party):
Gagan Joshi, Massachusetts General Hospital

Brief Summary:
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 or disease Intervention/treatment Phase
Autism Spectrum Disorder Drug: Memantine Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
Actual Study Start Date : November 2014
Actual Primary Completion Date : May 7, 2018
Actual Study Completion Date : May 7, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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
Experimental: Memantine
Memantine administered in tablet form twice daily titrated to a maximum dose of 20 mg for 12 weeks
Drug: Memantine
Other Name: Namenda

No Intervention: Control Group
Healthy volunteers will be scanned twice (10-12 weeks apart) and will receive no intervention.

Primary Outcome Measures :
  1. Social Responsiveness Scale-Second Edition (SRS-2) [ Time Frame: 12 Weeks ]
    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

  2. Clinical Global Impression-Improvement (CGI-I) subscale [ Time Frame: 12 Weeks ]
    The CGI-I is a measure of illness improvement.

Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria (all participants)

1. Male & female subjects ages 8-17 years (inclusive).

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) 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) & 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 ≤70 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. Lamotrigine
    2. Amantadine
    3. N-acetylcysteine
    4. D-cycloserine
  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. 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
  6. Initiation of a new psychosocial intervention within 30 days prior to randomization.
  7. Contraindications to MR scanning (claustrophobia, braces, metal in the body, etc.)
  8. Subjects who are pregnant and/or nursing.
  9. Subjects with a history of non-febrile seizures without a clear and resolved etiology.
  10. Subjects with a history of or a current liver or kidney disease.
  11. Clinically unstable psychiatric conditions or judged to be at serious suicidal risk.
  12. History of substance use (except caffeine) within past 3 months
  13. Serious, stable or unstable systemic illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
  14. Subjects with severe hepatic impairment (LFTs > 3 times ULN).
  15. Subjects with genitourinary conditions that raise urine pH (e.g., renal tubular acidosis, severe infection of the urinary tract).
  16. Known hypersensitivity to memantine.
  17. Severe allergies or multiple adverse drug reactions.
  18. A non-responder or history of intolerance to memantine, after treatment at adequate doses as determined by the clinician.
  19. Investigator and his/her immediate family defined as the investigator's spouse, parent, child, grandparent, or grandchild.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01972074

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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Mclean Hospital
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Principal Investigator: Gagan Joshi, MD Massachusetts General Hospital

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Responsible Party: Gagan Joshi, Assistant Professor of Psychiatry, Harvard Medical School; Director, Bressler Program for Autism Spectrum Disorders, Pediatric Psychopharmacology, Massachusetts General Hospital, Massachusetts General Hospital Identifier: NCT01972074     History of Changes
Other Study ID Numbers: 2013-P-001826
First Posted: October 30, 2013    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: October 2018

Keywords provided by Gagan Joshi, Massachusetts General Hospital:
Autism spectrum disorder
functional Magnetic Resonance Imaging

Additional relevant MeSH terms:
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Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Pathologic Processes
Neurodevelopmental Disorders
Mental Disorders
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents