Study of Aripiprazole (Abilify) Versus Placebo in Children With Subsyndromal Bipolar Disorder

Phase 3

Completed

• Conditions: Bipolar Disorder
• Interventions: Drug: Placebo; Drug: Aripiprazole

• Registration Number: NCT00194012
• Lead Sponsor: University Hospitals Cleveland Medical Center

Brief Summary

The purpose of this study is to test the effectiveness and tolerability/safety of aripiprazole (Abilify) in children with subsyndromal symptoms of bipolar disorder who also have a parent with bipolar disorder and other family member with a mood disorder.

Detailed Description

This will be a double-blind, placebo-controlled, parallel-arm, randomized clinical trial that will last up to 12 weeks.

This placebo-controlled portion will be followed by a 6-week open label extension/stabilization phase. In order to be eligible for participation in the extension/stabilization phase, subjects must: 1) in the investigator's opinion have had no dose-limiting side effects likely to be attributable to aripiprazole (APZ); 2) participated in the blinded portion of the clinical trial for a minimum of 4 weeks.

Study Timeline

• Study Start: 2004-08
• Study First Submitted: 2005-09-11
• Study First Submitted QC: 2005-09-11
• Study First Posted: 2005-09-19
• Primary Completion: 2012-05
• Study Completion: 2012-06
• Results First Submitted: 2013-06-26
• Results First Submitted QC: 2014-04-04
• Results First Posted: 2014-05-05
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-02
• Last Update Posted: 2017-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 62

Inclusion Criteria

• Outpatients ages 5-17 years (inclusive)
• Patients, who in the investigator's opinion have substantial symptoms of mania, depression, or both within the past 2 weeks such that treatment with a pharmacological agent is warranted
• Currently meets Diagnostic Statistical Manual of Mental Disorders (DSM-IV) criteria for either cyclothymia, or bipolar disorder not otherwise specified (BP NOS) based on the results of both a semi-structured diagnostic research assessment, Present and Lifetime Version (K-SADS-Present and Lifetime (PL) supplemented with sections from the Washington University K-SADS) (Geller et al., 2001; Kaufman et al., 1997) and a clinical interview with a child and adolescent psychiatrist.
• Offspring of a parent with a bipolar spectrum disorder (based on the results of either the Mini International Neuropsychiatric Interview (MINI)(Sheehan et al., 1998) or the Family History Method (FH-RDC)(Andreasen et al., 1977)
• Has another first or second degree relative with a mood disorder determined by the results of either the MINI or the FH-RDC
• Has participated in at least 4 sessions of psychotherapy specifically focused on the symptoms/management of pediatric mood disorder and continues to have clinically significant symptomatology

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Exclusion Criteria

• Patients who have a history of intolerance to APZ at doses of 0.1mg/kg/day
• Patients who have experienced a manic episode with documented treatment with APZ monotherapy at a dose of 0.2 mg/kg/day
• Patients with an active neurological/medical disorder for which treatment with APZ would be contraindicated
• Patients with clinical evidence of autistic disorder, Asperger's disorder, Rett's syndrome or other pervasive developmental disorder
• Patients with clinical evidence of mental retardation
• Patients who are known to be allergic or hypersensitive to aripiprazole
• Patients who are unable to swallow pills/capsules
• Patients for whom the need for hospitalization during the course of the study appears likely
• Patients who have started a new psychotherapeutic intervention within less than 4 weeks of randomization
• Patients who have a general medical or neurological condition (including clinically significant abnormalities on screening laboratories) that may be considered to be the etiology of the patient's mood disorder
• Patients who have a general medical or neurological condition for which treatment with an atypical antipsychotic would be contraindicated (e.g. tardive dyskinesia)
• Patients who have a general medical or neurological condition that could interfere with the interpretation of clinical response to APZ treatment
• Patients taking psychotropic agents (other than psychostimulants) within one week of baseline (2 weeks for fluoxetine; 3 days for psychostimulants)
• Patients with a suicide attempt requiring medical/psychiatric care within the past 6 months
• Has met DSM-IV criteria for drug/alcohol abuse or dependence within the past 6 months
• Females who are currently pregnant or lactating
• Sexually active females, who in the investigators' opinion are not using an adequate form of birth control

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo-Randomized Phase	Placebo	Patients randomly assigned to placebo received pills/dosing made to look identical to the aripiprazole.
Aripiprazole-Randomized Phase	Aripiprazole	Patients randomly assigned to aripiprazole received medication in pill form with dosing at 2mg, 5mg, 7mg, 10mg, 12mg or 15mg depending on their response.

Primary Outcome Measures

Name	Time	Method
Young Mania Rating Scale (YMRS)	Open-Label Extension - 6 weeks	The Young Mania Rating Scale (YMRS) has 11 items and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours. Additional information is based upon clinical observations made during the course of the clinical interview. The items are selected based upon published descriptions of the core symptoms of mania. Each item o the YMRS is given a severity rating. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients. There are well described anchor points for each grade of severity. Total score ranges from 0 to 60, with higher being more severe mania.

Secondary Outcome Measures

Name	Time	Method
Children's Depression Rating Scale-Revised (CDRS-R )	Baseline	The CDRS-R is a rating scale used to assess severity of depression and change in depressive symptoms in children and adolescents. The CDRS-R is a 17-item scale administered by clinician's in interviews with a child/parent(s). Each item is scored on a range of 1-5 or 1-7 with a total possible score of 17-113. A score greater or equal to 40 is indicative of depression and a score less than or equal to 28 is typically means few or no depressive symptoms.
CDRS-R Children's Depression Rating Scale-Revised	Open-Label Extension - 6 weeks	The CDRS-R is a rating scale used to assess severity of depression and change in depressive symptoms in children and adolescents. The CDRS-R is a 17-item scale administered by clinician's in interviews with a child/parent(s). Each item is scored on a range of 1-5 or 1-7 with a total possible score of 17-113. A score greater or equal to 40 is indicative of depression and a score less than or equal to 28 is typically means few or no depressive symptoms.
Children's Global Assessment Scale (CGAS)	Open-Label Extension - 6 weeks	Children's Global Assessment Scale (CGAS) is a scale that clinicians use in order to rate the general emotional and behavioral functioning of children and adolescents under age 18. The scoring range is either 1 to 100. Youth with higher scores indicate better functioning with 91-100 "Doing very well" to 1-10 Extremely impaired.; The score should be calculated separate from diagnosis, treatment or prognosis.
Clinical Global Impressions Scale (CGI-Severity)	Open-Label Extension - 6 weeks	Clinical Global Impressions Scale (CGI-Severity) is a physician-administered assessment designed to track progress over time on a wide range of psychiatric disorders. The CGI-Severity or CGI-S consists of one question about the extent of a patient's mental illness at the time of the assessment. Using a 7-point rating scale, clinicians rate the severity of mental illness based on an average of observed and reported symptoms, behavior and function during the past 7 days. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale IV or (ARS-IV)	Open-Label Extension - 6 weeks	The Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale IV or (ARS-IV) is a clinician-scored rating scale used to track the frequency of ADHD symptoms during the previous 1-week period. The ARS-IV contains 18 questions--(9 focused on inattention, and 9 on hyperactivity-impulsivity.) Questions are answered in a way that best describes ADHD symptom frequency--Never or Rarely=0, Sometimes=1, Often=2, or Very Often=3. The clinician adds up the responses for a total score. Higher total scores indicate a greater degree of symptoms being present. As a result, the minimum score is 0, and the maximum score is 54.

Trial Locations

Locations (1)

University Hospitals Case Medical Center - Walker Building; 🇺🇸 Cleveland, Ohio, United States