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

Autism Spectrum Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01972074
• Other study ID #: 2013-P-001826
• Status: Completed
• Phase: Phase 3
• Start date: February 17, 2015
• Est. completion date: May 7, 2018

Study information

• Verified date: September 2019
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a 12-week, randomized-controlled trial of memantine hydrochloride (Namenda) for the treatment of social impairment in adolescents with autism spectrum disorder (ASD). The investigators will also conduct pre- and post-treatment neuroimaging (functional magnetic resonance imaging [fMRI] and hydrogen magnetic resonance spectroscopy [HMRS]) to assess neural functional deficits in adolescents with autism spectrum disorder compared to healthy volunteer adolescents. This pre- and post-neuroimaging will also be used to assess any effects of memantine therapy on neural function in adolescents with autism spectrum disorder. 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 autism spectrum disorder. Additionally, the investigators hypothesize that following memantine therapy, adolescents with autism spectrum disorder 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 anterior cingulate cortex and medial temporal lobes, consistent with improvement in social impairments in autism spectrum disorder. The investigators hypothesize that compared to healthy volunteer participants, participants with autism spectrum disorder will significantly differ on neuroimaging measures at baseline but that following memantine therapy, the difference between autism spectrum disorder and healthy volunteer neuroimaging data will decrease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: May 7, 2018
• Est. primary completion date: May 7, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 17 Years

Eligibility

INCLUSION CRITERIA

All Participants:

1. Male and female participants, ages 8-17 years (inclusive)

Participants with Autism Spectrum Disorder:

2. Meets Diagnostic and Statistical Manual-5 autism spectrum disorder diagnostic criteria, as established by clinical diagnostic interview

3. 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 Autism Spectrum Disorder Clinical Global Impression-Severity scale (ASD CGI-S)

Healthy Control Participants:

2. Age-, sex-, and IQ-matched with participants with autism spectrum disorder 3. No Axis I diagnoses, as established by the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version (K-SADS-E) and confirmed by clinical diagnostic interview 4. No significant traits of autism spectrum disorder, as measured by a total raw score of <60 on the parent/guardian-completed Social Responsiveness Scale, Second Edition

EXCLUSION CRITERIA

All Participants:

1. IQ =70 based, on the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) Vocabulary and Matrix Reasoning subtests

2. Impaired communicative speech

3. Current treatment with the following medications, which are known to impact glutamate levels:

1. Lamotrigine

2. Amantadine

3. N-acetylcysteine

4. D-cycloserine

4. Current treatment 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. Participants who are pregnant and/or nursing

8. Participants with a history of non-febrile seizures without a clear and resolved etiology

9. Participants with a history of or a current liver or kidney disease

10. Clinically unstable psychiatric conditions or judged to be at serious suicidal risk

11. Participants who meet for alcohol or drug dependence or abuse on the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version. If the participant has a recent history of substance abuse, as an added precaution, there will be a 2-week washout period before initiating the trial. There are no known safety issues relating to memantine and recent history of substance abuse.

12. Serious, stable or unstable, systemic illness, including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease

13. Participants with severe hepatic impairment (Liver Function Tests [LFTs] >3 times the Upper Limit of Normal [ULN])

14. Participants with genitourinary conditions that raise urine Power of Hydrogen (pH) (e.g., renal tubular acidosis, severe infection of the urinary tract)

15. Known hypersensitivity to memantine

16. Severe allergies or multiple adverse drug reactions

17. A non-responder or history of intolerance to memantine after treatment at adequate doses, as determined by the clinician

18. Investigator and his/her immediate family, defined as the Investigator's spouse, parent, child, grandparent, or grandchild.

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive
• Disease

Intervention

Drug:
• Memantine
Capsule

Other:
• Placebo
Capsule

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Mclean Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Responder	Treatment responders are defined as having a 25% reduction, from baseline to endpoint, in Social Responsiveness Scale, Second Edition: School-Age, Parent Report (SRS-2) total raw score and an Autism Spectrum Disorder Clinical Global Impression-Improvement (ASD CGI-I) score =2. The Social Responsiveness Scale, Second Edition (SRS-2) is a 65-item rating scale completed by the parents/guardians of children ages 4-18. It is used to measure the severity of autism spectrum disorder symptoms. Each item is rated on a 4-point Likert scale, ranging from 1=Not True to 4=Almost Always True. Higher scores indicate a higher severity of autism spectrum disorder symptoms. The Autism Spectrum Disorder Clinical Global Impression-Improvement subscale (ASD CGI-I) is a clinician-rated measure of the improvement of autism spectrum disorder symptoms. The subscale is rated on a 7-point Likert scale, ranging from 1=Very Much Improved to 7=Very Much Worse. Higher scores indicate less symptom improvement.	12 Weeks (from Baseline [Week 0] to Endpoint [Week 12])