An Open-Label Trial of Aripiprazole in Autism Spectrum Disorders
Condition: Autism; Asperger's Disorder; Pervasive Developmental Disorder
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Developmental Disabilities; Asperger Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      The aim of this study is to evaluate the efficacy, safety and tolerability of aripiprazole
      monotherapy in the treatment of children and adolescents suffering from Autism Spectrum
      Disorder (ASD) over a 12-week period. We hypothesize that aripiprazole may be helpful in
      reducing ASD-associated symptoms of anxiety and aggression, resulting in significant
      improvements in global outcome.
    

Detailed description: 
      Study Design: Fifteen patients with DSM-IV diagnoses of Autism, Asperger's Disorder or
      Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS) will be enrolled in this
      12-week open-label study. Parents of potential subjects will do a preliminary phone screen,
      followed by a clinical evaluation by a psychiatrist for possible inclusion in the study.
      Informed written consent and assent will be obtained from the parents and subjects
      respectively once deemed competent and before the initiation of any study procedures.

      Clinical Evaluation will use the Autism Diagnostic Interview (ADI-R) and the Autism
      Diagnostic Observation Schedule (ADOS) to establish a formal diagnosis.

      Study Procedures Baseline Assessments: Many baseline measures for physical health will be
      done at the screening visit and during the first weekly visit. These will include a clinical
      interview, physical and neurological examination will be done during the screening period and
      height, weight and vital signs, and a calculation of his/her Body Mass Index (BMI) will be
      done during the screening period and during the first weekly visit. Laboratory measures at
      baseline and study completion will include a complete metabolic panel (with liver
      transaminases) and complete blood count with differential. Further measures will include a
      fasting lipid profile, hemoglobin A1C, prolactin level and insulin levels, and fasting blood
      sugar level (FBS). Serum albumin will be measured not only as a measure of nutritional state,
      but also in accordance with the fact that aripiprazole is 99% protein-bound. An
      electrocardiogram (ECG) will be performed at the beginning and end of the study to monitor
      for possible cardiac effects. These measures are aimed at monitoring side effects reported in
      the use of other medications in this class. Urine pregnancy tests will be performed for each
      female subject at the beginning and end of the study.

      Outcome measures will include the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Brief
      Psychiatric Rating Scale for children (BPRS-C), Clinical Global Impression - Severity
      (CGI-S), Vineland Adaptive Behavior Scale (VABS) and the Atypical Children's Development
      Scale (ACDS).

      Baseline parameters for extrapyramidal side effects will be established using the Abnormal
      Involuntary Movement Scale (AIMS), the Simpson Angus Extrapyramidal Side Effect Scale (SAEPS)
      and the Barnes Akathisia Rating Scale. Baseline values for general side effects will be
      compiled using the Monitoring of Side Effects System (MOSES).

      Weekly visits: At all visits, patients will undergo a clinical interview, vital signs, and
      weight measures. Custodial guardian(s) will provide collateral information. The weekly
      "short" visits will occur at weeks 2, 4, 6, 8, 10 and 12. They will be about 45 minutes in
      duration.

      Ongoing outcome measures will be performed at visits 3, 5, 7, 9 and 11. The visits will be
      about 1-1.5 hours in duration. The measures done will include those at the short visits, as
      well as the Y-BOCS, BPRS, ABC and CGI-S. Side effects will be monitored using the AIMS,
      SAEPS, Barnes Akathisia Scale and MOSES at these visits.

      Termination Visit: The last visit (Visit 13 or earlier if patient drops out of the study)
      will include the repetition of all measures at visit 1 (except the ADI-R) and will last about
      2 hours. All baseline laboratory measures will be repeated at this time.

      Follow-Up Patient Care: After completion of the clinical trial, the patients will be followed
      at the Cambridge Health Alliance (CHA) Center for Child and Adolescent Development until they
      can be referred back to their original psychiatric providers or to appropriate treatment
      providers in the community.

      Medication dosing: Aripiprazole will be started at 2.5mg or 5mg depending on clinical
      impression and severity of especially aggression and agitation. At the weekly visits, the
      dose will be adjusted in not more than 5mg increments according to clinical impression. The
      lowest effective dose will be used, up to a maximum dose of 20mg.

      Patients already taking psychotropic medications will be tapered off their medications during
      the first 1-2 weeks of the study. The dose will be reduced to 67% of the initial dose for 3
      days and then to 33% of the initial dose for 3 days and then the medication(s) will be
      discontinued. The subjects will remain off of on enrollment medications for 5 half lives and
      then aripiprazole will be initiated. Anticonvulsant medications taken for seizure control may
      be continued throughout the trial as long as the subject has been on a stable dose for 30
      days prior to the study and has been seizure free for 6 months. These medication doses will
      be held stable throughout the trial.

      Adverse Events: Any serious adverse event leading to hospitalization will lead to study
      discontinuation. Any event requiring concomitant medication(s) will also lead to
      discontinuation. Adverse events will be reported to the Institutional Review Board (IRB) if
      there is an event requiring medical attention, or scores 3 or higher on the MOSES scale.
      Also, failure to comply with the study instructions will result in termination from the
      protocol.
    

Intervention name(s): Aripiprazole
Intervention type(s): Drug
Intervention description(s): open-label, flexible-dosing
Other intervention name(s): Abilify
Intervention MeSH terms: Aripiprazole
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: behavioral problems; aggression; autism; aripiprazole