Please select the eligibility criteria that correspond to the clinical trial below.
Title: Biomarkers in Autism of Aripiprazole and Risperidone Treatment
Brief Summary: The Biomarkers in autism of aripiprazole and risperidone treatment (BAART) project will provide evidence-based guidance in the selection and monitoring of drug treatment of autism. BAART involves 3 academic centers across South Carolina. Although the FDA has approved use of the antipsychotic drug risperidone for irritability associated with autistic disorder, a moderate response rate in pivotal clinical trials and concerns over tolerability and weight gain can force clinicians to select alternative drug treatments for which evidence-based support is sparse.


Options:
A: Inclusion Criteria

* Aged 6 to 17 years and weight of at least 15 kg
* Meet DSM-IV criteria for of AD, established by chart review, clinical judgment and the Autism Diagnostic Interview- Revised (ADI-R) criteria
* Clinical Global Impressions Severity (CGI-S) score of \>4 (moderately ill)
* ABC Irritability subscale score of \>18
* Mental age of at least 18 months
* If female and sexually active, must agree to an acceptable method of birth control during the trial
* Medication free or adequate washout period (2-4 weeks prior to enrollment) of psychoactive drugs (anticonvulsants permitted for seizure management if dosage is stable for 4 weeks)
* Parent/guardian able to read and provide informed consent.

Exclusion Criteria

* Psychiatric disorder that is effectively managed by psychoactive medication (e.g. ADHD, MDD)
* Prior diagnosis or evidence of genetic or other disorder that may interfere with assessments (e.g. Fragile X syndrome, Fetal alcohol syndrome, history of very low birth weight) assessed by personal and family history, dysmorphology, and clinical judgment.
* Prior use of risperidone or aripiprazole for more than 2 weeks
* Seizure during the past 6 months
* History or evidence of a medical condition that would expose them to an undue risk of a significant adverse event or interfere with assessments during the trial including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, hematologic or immunologic disease as determined by the clinical judgment of the investigator
* Current suicidal or homicidal risk
* Positive urine pregnancy test at baseline
* Dependent on other substances, with the exception of nicotine or caffeine
B: Inclusion Criteria:

* Fluent in English
* Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for ASD or International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD10) criteria for Autism diagnosis confirmed by Autism Diagnostic Observational Schedule (ADOS-2) criteria
* Social Responsiveness Scale, second edition (SRS-2) (T-score) \>= 66
* Clinical Global Impressions of Severity (CGI-S) \>= 4 (moderately ill) at screening
* IQ \>= 70 as assessed by Wechsler Abbreviated Scale of Intelligence Scale: Second Edition (WASI-II) or Wechsler Preschool and Primary Scale of Intelligence: Fourth Edition (WPPSI-IV) intelligence test
* Language, hearing, and vision compatible with the study measurements as judged by the investigator

Inclusion Criteria for the OLE:

* Have completed the blinded treatment phase of the study OR were required to stop dosing at or before Week 8
* Have no adverse events that would prohibit starting the OLE

Exclusion Criteria:

* Initiation of a major change in psychosocial intervention (including investigational) within 4 weeks prior to screening
* Unstable or uncontrolled clinically significant psychiatric and/or neurological disorder that may interfere with the safety or efficacy endpoints
* Known personal or family history of cerebral aneurysm
* Risk of suicidal behavior
* Seizure within the past 6 months
* Medical history of alcohol or substance abuse/dependence
* Concurrent cardio-vascular disease not considered well controlled by the Investigator
* Clinically significant abnormality on electrocardiogram at screening
* Concomitant disease or condition (pulmonary, gastro-intestinal, hepatic, renal, metabolic, immunological system, or obesity that could interfere with the conduct of the study
* Evidence for current gastro-intestinal bleeding, e.g., active stomach ulcer disease
* History of coagulopathies, bleeding disorders, or blood dyscrasias
* Positive serology for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) 1, or HIV 2
* Confirmed clinically significant abnormality in parameters of hematology, clinical chemistry, coagulation, or urinalysis
* Medical history of malignancy if not considered cured
* Participation in an investigational drug study within 90 days or 5 times the half-life of the investigational molecule (whichever is longer) prior to randomization
* Loss of blood over 250 milliliters within three months prior to screening
* Allowed medications have not been stable since 4 weeks before screening, and allowed medications for treatment of epilepsy have not been stable since 3 months before screening
* Use of prohibited medications within 2 weeks prior to screening visit or 5 times the half-life prior to randomization (whichever is longer)
C: Inclusion Criteria:

* Males and females between the ages of 5 and 17 years 2 months.
* Weight of 15 kg or greater.
* DSM-IV diagnosis of Autistic Disorder.
* Inpatient or outpatient.
* Medication free for at least 2 weeks for all psychotropic medications (4 weeks for fluoxetine or depot neuroleptics).
* Anticonvulsants used for treatment of seizure disorder permitted if the dosage has been stable for 4 weeks and patient seizure free for at least 6 months.
* Clinical Global Impression Severity score of at least 4 and a)18 or greater on the Irritability Scale of the Aberrant Behavior Checklist or b) .5 total score on the Ritvo-Freeman scale.
* Mental age of at least 18 months.
* Negative pregnancy test

Exclusion Criteria:

* IQ below 18 months.
* Females with a positive pregnancy test. - Evidence of a prior adequate trial with risperidone.
* Evidence of hypersensitivity to risperidone.
* Past history of neuroleptic malignant syndrome.
* DSM-IV diagnosis of Pervasive Developmental Disorder other than Autistic Disorder.
* Significant medical condition such as heart disease, hypertension, liver or renal failure, pulmonary disease, or unstable seizure disorder.
* Weight less than 15 kg.
D: Inclusion Criteria:

* Age ≥ 12 and \< 26 years.
* Weight greater than 50 kg.
* Diagnosis of ASD
* Drug-refractory irritability, as defined as screening ABC Irritability subscale (ABC-I) score of ≥18 AND 1) failure of clinically adequate treatment trials of both aripiprazole and risperidone or 2) failure of at least three previous clinically adequate drug trials targeting irritability (one trial must include aripiprazole or risperidone), as confirmed by caregiver reports and medical record review when available.
* Stable dosing of all concomitant psychotropic medications (including those targeting irritability) for four weeks prior to screening visit and during the study.
* Presence of parent/guardian willing to serve as informant for behavioral outcome measures and shipping control sample for Extracellular Signal-Related Kinase biomarker (ERK) assay.

Exclusion Criteria:

* Current use of more than two concomitant psychotropic drugs targeting irritability.
* Current use of valproic acid.
* Current use of drugs with known interaction with riluzole
* Current use of drugs with concomitant glutamatergic or glutamatergic- modulating action medications.
* For female subjects of child bearing potential, a positive serum pregnancy test.
* History of pancreatitis.
* Hemoglobin less than or equal to 8.0 gm/dL.
* Neutropenia with absolute neutrophil count less than or equal to 1.0 K/mcL.
* Problems with kidney functioning, as assessed by lab work
* Any major chronic medical or chronic respiratory illness considered to be uncontrolled by the Principal Investigator.

Answer: A