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Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders

Primary Purpose

Pervasive Developmental Disorder

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Aripiprazole oral product

Placebo oral capsule

About this trial

This is an interventional treatment trial for Pervasive Developmental Disorder focused on measuring PDD NOS

Eligibility Criteria

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

Inclusion Criteria:

Male and female outpatients between the ages of 5 and 17 years and greater than or equal to 15 kg body weight.
Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revised (DSM-IV-TR) diagnosis of Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS).
Psychotropic medication-free for at least 2 days prior to screening laboratory tests and electrocardiogram (ECG).
Significant irritability as determined by a Clinical Global Impression Severity score of greater or equal to 4 (Moderately ill) and a score of equal to or greater than 18 on the Aberrant Behavior Checklist Irritability Subscale.
Intelligence quotient (IQ) of equal to or greater than 50 based on the Wechsler Intelligence Scale for Children (WISC), 4th edition; the Leiter International Test of Intelligence-Revised will be used if a child is nonverbal but thought to have an IQ greater than or equal to 50.

Exclusion Criteria:

DSM-IV-TR diagnosis other than PDD NOS (autistic disorder, Asperger's disorder, Rett's disorder, or childhood disintegrative disorder), schizophrenia, bipolar disorder or substance abuse within the last 6 months.
Comorbid disorder with possible association to autism (e.g., Fragile X Syndrome, Tuberous Sclerosis).
A significant medical condition such as heart, liver, renal, or pulmonary disease, or a seizure disorder, as determined by history, physical examination, or laboratory testing.
Subjects with an active seizure disorder (history of febrile seizures in early childhood will be considered.
Females with a positive urine pregnancy test.
Evidence of a prior adequate trial of aripiprazole (defined as equal to or greater than 2 weeks at equal to or greater than 5 mg per day. When there is not evidence of a prior adequate trial, subjects must be medication-free for a least 2 weeks prior to baseline.
History of neuroleptic malignant syndrome.
Subjects who, in the opinion of the investigator, are unsuitable in any other way to participate in this study, including being unable to comply with the requirements of the study for any reason.
Hypersensitivity to aripiprazole [e.g., allergic response or serious adverse effect] (significant tachycardia).

Sites / Locations

Riley Hospital for Children, Christian Sarkine Autism Treatment Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm 1. Aripiprazole oral product

Arm 2. Placebo oral capsule

Arm Description

Participants will receive Aripiprazole oral product with a minimum dose of 2 mg per day to a maximum dose of 20 mg per day over 8-weeks of treatment.

Participants will receive matching (identical in size and appearance to study drug) placebo oral capsules over 8-weeks of treatment.

Outcomes

Primary Outcome Measures

Number of Participants Improved as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2)

Clinical Global Impressions (Guy, 1976) global improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7, with lower scores indicating greater improvement (1=very much improved and 2=much improved). Participants with a CGI-I score of 1 or 2 were classified as improved. Four participants assigned to placebo completed an exit interview prior to week 8. One participant assigned to placebo and one participant assigned to aripiprazole withdrew from the study without completing an exit interview.

Mean Post-baseline Aberrant Behavior Checklist Irritability Subscale Score, Parent Report, Double-blind Phase

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Irritability subscale is 0 to 45. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints. Confidence intervals reflect a Bonferroni multiple testing correction accounting for the selection of two primary outcomes.

Secondary Outcome Measures

Mean Post-baseline Aberrant Behavior Checklist Hyperactivity Subscale Score, Parent Report, Double-blind Phase

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers overactivity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores is 0 to 48 on the Hyperactivity subscale. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.

Mean Post-baseline Aberrant Behavior Checklist Inappropriate Speech Subscale Score, Parent Report, Double-blind Phase

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Inappropriate Speech subscale is 0 to 12. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.

Mean Post-baseline Aberrant Behavior Checklist Social Withdrawal Subscale Score, Parent Report, Double-blind Phase

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item Parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Social Withdrawal subscale is 0 to 48. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.

Mean Post-baseline Aberrant Behavior Checklist Stereotypy Subscale Score, Parent Report, Double-blind Phase

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Stereotypy subscale is 0 to 21. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.

Full Information

NCT ID

NCT00870727

First Posted

February 2, 2009

Last Updated

December 7, 2018

Sponsor

Indiana University

Collaborators

National Institute of Mental Health (NIMH), Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT00870727

Brief Title

Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders

Official Title

Pharmacotherapy of Pervasive Developmental Disorders

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

February 2009 (undefined)

Primary Completion Date

March 2015 (Actual)

Study Completion Date

May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Indiana University

Collaborators

National Institute of Mental Health (NIMH), Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to develop a better tolerated and more effective pharmacologic treatment with individuals with Pervasive Developmental Disorder. This is a double-blind, placebo-controlled study of aripiprazole in the management of the maladaptive behaviors of Pervasive Developmental Disorder. The investigators hypothesize that aripiprazole will be more effective than placebo for reducing aggression, tantrum and self-injurious behavior in children with Pervasive Developmental Disorder.

Detailed Description

Pervasive developmental disorders (PDDs) are characterized by severe impairments in social interaction and communication in addition to restricted patterns of interests and activities. Research suggests that a dysregulation of the dopamine and serotonin systems contributes to these interfering behaviors in individuals with PDD. After benefits of typical neuroleptics were reported in subjects with PDD, research shifted to the atypical antipsychotics which have been shown to be better tolerated and effective in this population. However, the atypical antipsychotics have also been associated with adverse effects. Thus there remains a need for a novel pharmacotherapy that would be safe and effective for children and adolescents with PDDs. The primary objectives of this study are to determine whether aripiprazole is effective and well tolerated for irritability in children and adolescents with PDD not otherwise specified (NOS) during an 8-week acute phase and whether the effectiveness and tolerability of aripiprazole is maintained during a 16-week continuation phase.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pervasive Developmental Disorder

Keywords

PDD NOS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1. Aripiprazole oral product

Arm Type

Experimental

Arm Description

Participants will receive Aripiprazole oral product with a minimum dose of 2 mg per day to a maximum dose of 20 mg per day over 8-weeks of treatment.

Arm Title

Arm 2. Placebo oral capsule

Arm Type

Placebo Comparator

Arm Description

Participants will receive matching (identical in size and appearance to study drug) placebo oral capsules over 8-weeks of treatment.

Intervention Type

Drug

Intervention Name(s)

Aripiprazole oral product

Other Intervention Name(s)

Abilify

Intervention Description

Minimum dose of 2 mg per day to a maximum dose of 20 mg per day over 8-weeks of treatment.

Intervention Type

Drug

Intervention Name(s)

Placebo oral capsule

Other Intervention Name(s)

Sugar pill

Intervention Description

Placebo will be identical in size and appearance to study drug.

Primary Outcome Measure Information:

Title

Number of Participants Improved as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2)

Description

Time Frame

Double-blind phase study exit - up to 8 weeks

Title

Mean Post-baseline Aberrant Behavior Checklist Irritability Subscale Score, Parent Report, Double-blind Phase

Description

Time Frame

Weeks 1, 2, 3, 4, 6 and 8

Secondary Outcome Measure Information:

Title

Mean Post-baseline Aberrant Behavior Checklist Hyperactivity Subscale Score, Parent Report, Double-blind Phase

Description

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers overactivity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores is 0 to 48 on the Hyperactivity subscale. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.

Time Frame

Weeks 1, 2, 3, 4, 6 and 8

Title

Mean Post-baseline Aberrant Behavior Checklist Inappropriate Speech Subscale Score, Parent Report, Double-blind Phase

Description

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Inappropriate Speech subscale is 0 to 12. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.

Time Frame

Weeks 1, 2, 3, 4, 6 and 8

Title

Mean Post-baseline Aberrant Behavior Checklist Social Withdrawal Subscale Score, Parent Report, Double-blind Phase

Description

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item Parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Social Withdrawal subscale is 0 to 48. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.

Time Frame

Weeks 1, 2, 3, 4, 6 and 8

Title

Mean Post-baseline Aberrant Behavior Checklist Stereotypy Subscale Score, Parent Report, Double-blind Phase

Description

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Stereotypy subscale is 0 to 21. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.

Time Frame

Weeks 1, 2, 3, 4, 6 and 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male and female outpatients between the ages of 5 and 17 years and greater than or equal to 15 kg body weight. Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revised (DSM-IV-TR) diagnosis of Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS). Psychotropic medication-free for at least 2 days prior to screening laboratory tests and electrocardiogram (ECG). Significant irritability as determined by a Clinical Global Impression Severity score of greater or equal to 4 (Moderately ill) and a score of equal to or greater than 18 on the Aberrant Behavior Checklist Irritability Subscale. Intelligence quotient (IQ) of equal to or greater than 50 based on the Wechsler Intelligence Scale for Children (WISC), 4th edition; the Leiter International Test of Intelligence-Revised will be used if a child is nonverbal but thought to have an IQ greater than or equal to 50. Exclusion Criteria: DSM-IV-TR diagnosis other than PDD NOS (autistic disorder, Asperger's disorder, Rett's disorder, or childhood disintegrative disorder), schizophrenia, bipolar disorder or substance abuse within the last 6 months. Comorbid disorder with possible association to autism (e.g., Fragile X Syndrome, Tuberous Sclerosis). A significant medical condition such as heart, liver, renal, or pulmonary disease, or a seizure disorder, as determined by history, physical examination, or laboratory testing. Subjects with an active seizure disorder (history of febrile seizures in early childhood will be considered. Females with a positive urine pregnancy test. Evidence of a prior adequate trial of aripiprazole (defined as equal to or greater than 2 weeks at equal to or greater than 5 mg per day. When there is not evidence of a prior adequate trial, subjects must be medication-free for a least 2 weeks prior to baseline. History of neuroleptic malignant syndrome. Subjects who, in the opinion of the investigator, are unsuitable in any other way to participate in this study, including being unable to comply with the requirements of the study for any reason. Hypersensitivity to aripiprazole [e.g., allergic response or serious adverse effect] (significant tachycardia).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kimberly A. Stigler, MD

Organizational Affiliation

Indiana University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Riley Hospital for Children, Christian Sarkine Autism Treatment Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

12. IPD Sharing Statement

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Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders

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