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An Open-Label Trial of Aripiprazole in Autism Spectrum Disorders

Primary Purpose

Autism, Asperger's Disorder, Pervasive Developmental Disorder

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aripiprazole
Sponsored by
Cambridge Health Alliance
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autism focused on measuring behavioral problems, aggression, autism, aripiprazole

Eligibility Criteria

6 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Males and Females ages 6-17 A diagnosis of Autism, Asperger's Disorder, or Pervasive Developmental Disorder - not otherwise specified (PDD NOS) Medically healthy Ability to give assent Significant tantrums, aggression, self-injurious behavior and/or agitation by achieving a score of 18 or higher on the Aberrant Behavior Checklist-irritability subscale and a score of moderate or higher on the Clinical Global Impressions-Severity Scale. Exclusion Criteria: Co-morbid serious mental illness. Intelligence Quotient (IQ) <50, based on verified records of cognitive testing performed within 2 years of enrollment. In event that suitable records of prior testing are unavailable, IQ will be estimated using the Wechsler Abbreviated Scale of Intelligence (WASI, 1999 Harcourt Assessment, Inc.). Significant active medical and/or neurological illness. Subjects that require other psychotropic medications such as antidepressants, mood stabilizers, anticonvulsants, stimulants, sedatives, or other antipsychotic medications in order to maintain clinical stability. Active substance abuse/dependence based upon history and urine toxicology screen. Inability to have blood drawn at baseline and termination visits. Known allergy or hypersensitivity to aripiprazole or its ingredients. Patients clinically stable on current medications.

Sites / Locations

  • Cambridge Health Alliance

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Aripiprazole

Arm Description

aripiprazole monotherapy, begun at 2.5 mg or 5.0 mg based on clinical impression and severity of aggression and agitation. Dose to be adjusted in not more than 5 mg increments, weekly. The lowest effective dose will be used up to a maximum daily dose of 20 mg.

Outcomes

Primary Outcome Measures

Clinical Global Impressions-Improvement
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to evaluate how much the patient's illness has improved or worsened compared to their baseline condition at the beginning of the intervention. The ratings are evaluated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Aberrant Behavior Checklist-Irritability Subscale
Aberrant Behavior Checklist (ABC) The ABC is a 58 item symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. Items are rated on a 4-point scale (0=no problem to 3=severe problem). A decrease in score indicates improvement. There are five subscales: a) Irritability and Agitation b) Lethargy and Social Withdrawal c) Stereotypic Behavior d) Hyperactivity and Noncompliance and e) Inappropriate Speech.This study uses the Irritability subscale for its outcome. The Irritability subscale is the sum of 15 items. Each item is rated using the scale: 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The Irritability subscale total score ranges from 0 to 45. A decrease in score over time indicates improvement.

Secondary Outcome Measures

Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
10-item assessment of obsessive-compulsive symptoms in patients less than 18 years of age. There are 5 items pertaining to compulsions rate symptoms (time spent, interference with functioning, distress, resistance, control) on a 5-point scale ( from 0=no symptoms/minimum severity, to 4=extreme symptoms/maximum severity). Total is the sum of 10 items. The range of possible totals is 0 (no symptoms) to 40 (severe). A decrease in value indicates improvement.
Brief Psychiatric Rating Scale for Children (BPRS-C)
The Brief Psychiatric Rating Scale for Children is a 21-item rating scale to evaluate psychiatric problems based on the clinician' s interview with the child/adolescent and parents. It has 7 scales: behavioral problems, depression, thought disorders, psychomotor excitation, withdrawal-retardation, anxiety, organicity. Ratings are based on a 7 point scale, from "Not Present" (scores 0) to "Extremely Severe" (scores 6 points). Total is the sum of the 21 items. The range of possible totals is 0 (no symptoms) to 126 (extremely severe).A decrease in score indicates improvement.

Full Information

First Posted
March 28, 2006
Last Updated
December 30, 2016
Sponsor
Cambridge Health Alliance
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00308074
Brief Title
An Open-Label Trial of Aripiprazole in Autism Spectrum Disorders
Official Title
A Prospective Open-Label Trial of Aripiprazole Monotherapy in the Autism Spectrum Disorders (ASD)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
February 2006 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
February 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cambridge Health Alliance
Collaborators
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism, Asperger's Disorder, Pervasive Developmental Disorder
Keywords
behavioral problems, aggression, autism, aripiprazole

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Aripiprazole
Arm Type
Experimental
Arm Description
aripiprazole monotherapy, begun at 2.5 mg or 5.0 mg based on clinical impression and severity of aggression and agitation. Dose to be adjusted in not more than 5 mg increments, weekly. The lowest effective dose will be used up to a maximum daily dose of 20 mg.
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Other Intervention Name(s)
Abilify
Intervention Description
open-label, flexible-dosing
Primary Outcome Measure Information:
Title
Clinical Global Impressions-Improvement
Description
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to evaluate how much the patient's illness has improved or worsened compared to their baseline condition at the beginning of the intervention. The ratings are evaluated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time Frame
Baseline, Endpoint using last observation carried forward (LOCF) at weeks 3,5,7,9,11 and 13.
Title
Aberrant Behavior Checklist-Irritability Subscale
Description
Aberrant Behavior Checklist (ABC) The ABC is a 58 item symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. Items are rated on a 4-point scale (0=no problem to 3=severe problem). A decrease in score indicates improvement. There are five subscales: a) Irritability and Agitation b) Lethargy and Social Withdrawal c) Stereotypic Behavior d) Hyperactivity and Noncompliance and e) Inappropriate Speech.This study uses the Irritability subscale for its outcome. The Irritability subscale is the sum of 15 items. Each item is rated using the scale: 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The Irritability subscale total score ranges from 0 to 45. A decrease in score over time indicates improvement.
Time Frame
Baseline, Endpoint using last observation carried forward (LOCF) at weeks 3,5,7,9,11 and 13.
Secondary Outcome Measure Information:
Title
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
Description
10-item assessment of obsessive-compulsive symptoms in patients less than 18 years of age. There are 5 items pertaining to compulsions rate symptoms (time spent, interference with functioning, distress, resistance, control) on a 5-point scale ( from 0=no symptoms/minimum severity, to 4=extreme symptoms/maximum severity). Total is the sum of 10 items. The range of possible totals is 0 (no symptoms) to 40 (severe). A decrease in value indicates improvement.
Time Frame
Baseline, Endpoint using last observation carried forward (LOCF) at weeks 3,5,7,9,11 and 13.
Title
Brief Psychiatric Rating Scale for Children (BPRS-C)
Description
The Brief Psychiatric Rating Scale for Children is a 21-item rating scale to evaluate psychiatric problems based on the clinician' s interview with the child/adolescent and parents. It has 7 scales: behavioral problems, depression, thought disorders, psychomotor excitation, withdrawal-retardation, anxiety, organicity. Ratings are based on a 7 point scale, from "Not Present" (scores 0) to "Extremely Severe" (scores 6 points). Total is the sum of the 21 items. The range of possible totals is 0 (no symptoms) to 126 (extremely severe).A decrease in score indicates improvement.
Time Frame
Baseline, Endpoint using last observation carried forward (LOCF) at weeks 3,5,7,9,11 and 13.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males and Females ages 6-17 A diagnosis of Autism, Asperger's Disorder, or Pervasive Developmental Disorder - not otherwise specified (PDD NOS) Medically healthy Ability to give assent Significant tantrums, aggression, self-injurious behavior and/or agitation by achieving a score of 18 or higher on the Aberrant Behavior Checklist-irritability subscale and a score of moderate or higher on the Clinical Global Impressions-Severity Scale. Exclusion Criteria: Co-morbid serious mental illness. Intelligence Quotient (IQ) <50, based on verified records of cognitive testing performed within 2 years of enrollment. In event that suitable records of prior testing are unavailable, IQ will be estimated using the Wechsler Abbreviated Scale of Intelligence (WASI, 1999 Harcourt Assessment, Inc.). Significant active medical and/or neurological illness. Subjects that require other psychotropic medications such as antidepressants, mood stabilizers, anticonvulsants, stimulants, sedatives, or other antipsychotic medications in order to maintain clinical stability. Active substance abuse/dependence based upon history and urine toxicology screen. Inability to have blood drawn at baseline and termination visits. Known allergy or hypersensitivity to aripiprazole or its ingredients. Patients clinically stable on current medications.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean A Frazier, MD
Organizational Affiliation
Cambridge Health Alliance
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cambridge Health Alliance
City
Medford
State/Province
Massachusetts
ZIP/Postal Code
02155
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.challiance.org/research/research.shtml
Description
Research program website

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An Open-Label Trial of Aripiprazole in Autism Spectrum Disorders

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