Please select the eligibility criteria that correspond to the clinical trial below.
Title: Memantine for the Treatment of Social Deficits in Youth with Disorders of Impaired Social Interactions: a Randomized-controlled Trial
Brief Summary: This study is a 12-week randomized-controlled trial of memantine hydrochloride (Namenda) for the treatment of social impairment in youth with Non-Verbal Learning Disorder, High-Functioning Autism Spectrum Disorder, and related conditions. Eligible participants will be males and females ages 8-18.

This study consists of up to 6 visits to Massachusetts General Hospital.


Options:
A: Inclusion Criteria:

* Age 3 Years to 12 Years
* Diagnostic Statistical Manual Version -IV (DSM-IV) and Autism Diagnostic Interview - Revised (ADI-R)-confirmed Diagnosis of Autistic Disorder
* Aberrant Behavior Checklist (ABC) Lethargy Subscale Score of 13 or greater

Exclusion Criteria:

* Children with Severe to Profound Mental Retardation
* Weight at Screening Visit \<11 kilograms
* Clinical Global Impressions-Severity Score of 7
* Presence of a Neurodevelopmental Disorder with Possible Associations to Autism: Subjects with Fragile X Syndrome, Tuberous Sclerosis, or other neurodevelopmental disorders known to be associated with autism or autistic features will be excluded.
* Presence of a Psychiatric Disorder that would Require a Specific Type of Treatment: Subjects with major depressive disorder, bipolar disorder, or a psychotic disorder will be excluded because treatment for these disorders often requires specific psychotropic agents. Subjects with an active substance use disorder will be excluded because of safety concerns and problems this would cause in assessing efficacy.
* Presence of a Medical Condition that would make Treatment with D-Cycloserine Less Safe: Subjects with significant cardiac, hepatic, or renal disease will be excluded due to concerns about pharmacokinetic alterations or adverse effects. Subjects with epilepsy or a history of seizures will be excluded due to rare reports of seizures with high doses of D-cycloserine. D-cycloserine is an U.S. FDA Pregnancy Category C drug. Because of the unknown effects of D-cycloserine on the developing human fetus, females of childbearing potential will be given a urine pregnancy test and required to use a suitable form of birth control during the study.
B: Inclusion Criteria:

* Male \& female subjects ages 8-18 years (inclusive).
* Diagnostic Statistical Manual (DSM)-5 Autism Spectrum Disorder (ASD) 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)14 and a score of ≥4 on the clinician-administered Clinical Global Impression-Severity scale (CGI-S)17.

Exclusion Criteria:

* IQ ≤70 based on the Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary and Matrix Reasoning subtests
* Impaired communicative speech
* Subjects currently treated with the following medications (known to impact glutamate levels): Lamotrigine, Amantadine, N-acetylcysteine, D-cycloserine
* 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.
* 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.
* Subjects who are pregnant and/or nursing.
* Subjects with a history of non-febrile seizures without a clear and resolved etiology.
* Subjects with a history of or a current liver or kidney disease.
* Clinically unstable psychiatric conditions or judged to be at serious suicidal risk.
* Subjects who meet on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-E) for alcohol or drug dependence or abuse. If the subject has a recent history of substance abuse, there will be a two-week washout period before initiating the trial as an added precaution. 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.
* Subjects with severe hepatic impairment (LFTs \> 3 times ULN).
* Subjects with genitourinary conditions that raise urine pH (e.g., renal tubular acidosis, severe infection of the urinary tract).
* Known hypersensitivity to memantine.
* Severe allergies or multiple adverse drug reactions.
* A history of intolerance or adequate exposure to memantine, as determined by the clinician.
* Investigator and his/her immediate family defined as the investigator's spouse, parent, child, grandparent, or grandchild.
C: Inclusion Criteria:

* Meet DSM-5 criteria for Autism Spectrum Disorder confirmed by the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule- Generic (ADOS-G)
* Children between the ages of 5-12 years of age
* Language delay (lack of fluent phrase speech) reflected by use of ADOS Module 1 or 2
* Must be on stable medication regimens for at least three months prior to enrollment, assuming the concomitant medication is safe for use with IGF-1

Exclusion Criteria:

* Closed epiphyses
* Active or suspected neoplasia
* Intracranial hypertension
* Hepatic insufficiency
* Renal insufficiency
* Cardiomegaly/valvulopathy
* History of allergy to IGF-1
* Patients with comorbid conditions deemed too medically compromised to tolerate the risk of experimental treatment with IGF-1
D: Inclusion Criteria:

* Autistic Disorder or Pervasive Developmental Disorder-Not Otherwise Specified
* Age 4-12
* General good health
* IQ of \>=36 or mental age of \>=18 months
* Parent/caregiver willingness to accompany child to clinic and monitor for side effects

Exclusion Criteria:

* Unstable Seizure Disorder
* Psychoactive medication in the process of adjustment
* Antipsychotic medication in previous 3 months before baseline
* Systemic corticoids (inhalers allowed)
* Planned beginning of major behavioral intervention in 3 months of study or the 2 months prior to the study.

Answer: B