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

Inclusion criteria

All Participants:

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

Participants with Autism Spectrum Disorder:

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

• 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:

• IQ ≤70 based, on the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) Vocabulary and Matrix Reasoning subtests
• Impaired communicative speech
• Current treatment with the following medications, which are known to impact glutamate levels:

• Lamotrigine
• Amantadine
• N-acetylcysteine
• D-cycloserine
• 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
• 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
• Initiation of a new psychosocial intervention within 30 days prior to randomization
• Participants who are pregnant and/or nursing
• Participants with a history of non-febrile seizures without a clear and resolved etiology
• Participants with a history of or a current liver or kidney disease
• Clinically unstable psychiatric conditions or judged to be at serious suicidal risk
• 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.
• Serious, stable or unstable, systemic illness, including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease
• Participants with severe hepatic impairment (Liver Function Tests [LFTs] >3 times the Upper Limit of Normal [ULN])
• Participants with genitourinary conditions that raise urine Power of Hydrogen (pH) (e.g., renal tubular acidosis, severe infection of the urinary tract)
• Known hypersensitivity to memantine
• Severe allergies or multiple adverse drug reactions
• A non-responder or history of intolerance to memantine after treatment at adequate doses, as determined by the clinician
• Investigator and his/her immediate family, defined as the Investigator's spouse, parent, child, grandparent, or grandchild.