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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Aripiprazole in At-Risk Children With Symptoms of Bipolar Disorder

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Aripiprazole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aripiprazole-Randomized Phase<br>Patients randomly assigned to aripiprazole received medication in pill form with dosing at 2mg, 5mg, 7mg, 10mg, 12mg or 15mg depending on their response. | Drug: Aripiprazole<br>* Addressed in arm description.<br>* Other names: Abilify;|
| Placebo Comparator: Placebo-Randomized Phase<br>Patients randomly assigned to placebo received pills/dosing made to look identical to the aripiprazole. | Drug: Placebo<br>* Addressed in arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Young Mania Rating Scale (YMRS) | 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. | Baseline | 
| Young Mania Rating Scale (YMRS) | 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. | 12 weeks | 
| Young Mania Rating Scale (YMRS) | 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. | Open-Label Extension - 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Children's Depression Rating Scale-Revised (CDRS-R ) | 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. | Baseline | 
| CDRS-R Children's Depression Rating Scale-Revised | 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. | 12 weeks | 
| CDRS-R Children's Depression Rating Scale-Revised | 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. | Open-Label Extension - 6 weeks | 
| Children's Global Assessment Scale (CGAS) | 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. | Baseline | 
| Children's Global Assessment Scale (CGAS) | 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. | 12 weeks | 
| Children's Global Assessment Scale (CGAS) | 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. | Open-Label Extension - 6 weeks | 
| Clinical Global Impressions Scale (CGI-Severity) | 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). | Baseline | 
| Clinical Global Impressions Scale (CGI-Severity) | 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). | 12 weeks | 
| Clinical Global Impressions Scale (CGI-Severity) | 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). | Open-Label Extension - 6 weeks | 
| Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale IV or (ARS-IV) | 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. | Baseline | 
| Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale IV or (ARS-IV) | 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. | 12 weeks | 
| Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale IV or (ARS-IV) | 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. | Open-Label Extension - 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bipolar disorder