Efficacy of Aripiprazole Versus Placebo in the Reduction of Aggressive and Aberrant Behavior in Autistic Children (Abilify)

Hypothesis: (1) Aripiprazole treatment will be superior to placebo in reducing aggression and irritability in autistic individuals as shown by reductions in the Aberrant Behavior Checklist-irritability subscale.

(2) Aripiprazole treatment will be superior to placebo in the acute treatment of global autism severity.

The purpose of this study is to examine the possible benefit of the medication Aripiprazole in autistic individuals.

Study Overview

• Status: Completed
• Conditions: Autism
• Intervention / Treatment: Drug: Aripiprazole; Drug: Placebos

Detailed Description

Aripiprazole is an atypical antipsychotic medication which is currently approved for the treatment of schizophrenia in adults. Multiple clinical trials in both children and adults have shown the effectiveness in the treatment of autism with medications like Aripiprazole. This study aims at assessing the effect of aripiprazole vs. placebo treatment on symptoms of irritability and aggression associated with autism, as well as the effect on the global severity of child and adolescent autistic disorder. Children or adolescent outpatients, with age ranges from 5-17, will be enrolled into an 8-week placebo controlled, double blind treatment study. During the 8 weeks, patients will be monitored by the treating psychiatrist. Study assessments will be administered at designated time points.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Piscataway, New Jersey, United States, 08854
      • Department of Child and Adolescent Psychiatry, University Behavioral Health Care Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meets DSM-IV, ADI-R criteria for autistic disorder.
• Age 5-17 years.
• Outpatients
• Parent or legal guardian willing to sign informed consent.

Exclusion Criteria:

• Subject has been diagnosed with a psychotic disorder (such as schizophrenia) or a mood disorder, including depression or bipolar disorder (manic depression).
• Subject has caused visible harm to him/herself.
• Subject has an active seizure disorder or epilepsy (seizures within the past year).
• Subject has an unstable medical illness, including heart disease.
• Subject has experienced brain injury.
• Subject has a history of diabetes.
• Subject reports significant improvement of autism symptoms and behaviors to current medication or other therapies.
• Subject has a history of prior treatment with Aripiprazole of 5 mg/day or higher for 6 weeks.
• Subject lives in a far away area and/or does not have regular access to transportation to the clinical facility.
• Subject is a pregnant female or unwilling to use acceptable contraception if sexually active.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aripiprazole; Subjects in the experimental group will receive Aripiprazole	Drug: Aripiprazole; Subjects under 40 kg will be started on 2.5mg per day of aripiprazole for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects; Other Names: Abilify
Placebo Comparator: Placebo; Subjects in the control group will receive sugar pill	Drug: Placebos; Inactive tablet made to resemble active tablet Subjects under 40 kg will be started on 2.5mg per day of placebo for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression Improvement (CGI-AD)	Clinical Global Impression Improvement (CGI)-AD (Guy, 1976). This is a standard rating scale with 7-point global severity and change scales which has been modified for Autistic Disorder. A rating of 2 is given when there is a substantial reduction in symptoms so that a treating clinician would be unlikely to change treatment. A rating of 1 is reserved for patients who become virtually symptom-free. A rating of 3 (minimally improved) on the CGI is defined as slight symptomatic improvement that is not deemed clinically significant. Administration time is approximately 2 minutes. Minimum is 1 and maximum is 5. A lower score indicates improvement, whereas a higher score indicates worsening.	Administered weekly, initial and week 8 reported

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aberrant Behavior Checklist	Aberrant Behavior Checklist (ABC) (irritability section) (Aman et al, 1985). The Aberrant Behavior Checklist assesses drug and other treatment effects on mentally retarded individuals. It consists of a five-factor scale comprising 58 items. We will use the Irritability section to assess aggressive and agitated behavior. While the internal consistency, validity and test-retest reliability were reported to be very good, inter-rater reliability was moderate (Aman et al, 1985). The ABC will be filled out by an informant, and then reviewed by the psychiatrist. Administration time is approximately 10 minutes. Maximum is 36, minimum is 0, a lower score indicates improvement.	Administered biweekly, initial and week 8 reported

Collaborators and Investigators

• Sponsor: University of Medicine and Dentistry of New Jersey
• Investigators: Principal Investigator: Sherie L. Novotny, MD, Child and Adolescent Psychiatry, UMDNJ

Publications and helpful links

General Publications

• Aman M, Smgh N, Stewart A, Field C. The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects.Am J Ment Defic, 1985a;89(5):485 491 Campbell M, et al, Neuroleptic related dyskinesias in autistic children: a prospective longitudinal study, J Am Acad Child Adolesc Psychiatry 1997; 36(6): 835 43. Fomboime E. The epidemiology of autism: a review. Psychological Medicine, 1999; 29:769 786. Guy W. ECDEU assessment manual for psychopharmacology. Revised. NTMH Publication DHEW Publ No (adm.) 76 388. Bethesda, MD: National Institute of Mental Health, 1976; 217 222. McDougle CJ, Holmes JP, Bronson MR, Anderson GM, Volkmar FR, Price LH, Cohen DJ. Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective open label study. J Am Acad Child Adolesc Psychiatry. 1997 May;36(5):685 93. Stahl SM. Dopamine system stabilizers, aripiprazole, and the next generation of antipsychotics, J Clin Psychiatry. 2001;62(l1).

Helpful Links

• Official site of the Division of Child and Adolescent Psychiatry

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: April 30, 2007
• First Submitted That Met QC Criteria: April 30, 2007
• First Posted (Estimate): May 2, 2007

Study Record Updates

• Last Update Posted (Actual): January 14, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Aggression; Irritability; Global autism severity
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Aggression; Autistic Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: 0220055441

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan at this time.