Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Psychiatric, Psychiatric, Autism |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 8 - 17 |
| Updated: | 10/21/2018 |
| Start Date: | November 2014 |
| End Date: | May 7, 2018 |
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.
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.
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.
We found this trial at
1
site
185 Cambridge Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
617-724-5200
Principal Investigator: Gagan Joshi, MD
Phone: 617-724-7079
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