Invega (Paliperidone) for the Treatment of Mania in Children and Adolescents Ages 6-17 With Bipolar Disorder

Study Overview
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Brief Summary
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This will be an 8-week open-label trial, using daily doses of paliperidone (Invega) in the treatment of children and adolescents who meet DSM-IV criteria of Bipolar I, Bipolar II, or Bipolar Spectrum Disorder. Specific hypotheses are as follows: Hypothesis 1: Bipolar Disorder symptomatology in children and adolescents with DSM-IV Bipolar I, Bipolar II, or Bipolar Spectrum Disorder will be responsive to Invega treatment. Hypothesis 2: Invega -associated improvement in bipolar disorder symptomatology in children and adolescents will translate into improved functional capacities (neuropsychological, social, and occupational), as well as an increased quality of life throughout treatment. Hypothesis 2: Invega treatment will be safe and well tolerated as reflected by a low drop out rate and absence of major side effects.

Detailed Description
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Invega (paliperidone), a second generation antipsychotic (SGA), is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives. Invega is approved by the FDA for the treatment of schizophrenia in adults. Initial data suggest a promising role for Invega in the treatment of bipolar disorder with minimal adverse events of weight gain. We propose to study the safety and efficacy of Invega therapy in children and adolescents with Bipolar I, Bipolar II, and Bipolar Spectrum Disorder. The study results will be used to generate hypotheses for a larger, randomized, controlled clinical trial with explicit hypotheses and sufficient statistical power. The proposed study includes 1) use of a 8-week design to document the response rate, 2) assessment of the impact of Invega on functional capacities (quality of life, psychosocial function) and cognition, and 3) careful assessment of safety and tolerability.

Official Title
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Open-Label Study of Invega for the Treatment of Mania in Children and Adolescents Ages 6-17 With Bipolar I, Bipolar II, and Bipolar Spectrum Disorder

Conditions
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Pediatric Bipolar Disorder

Intervention / Treatment
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* Drug: paliperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female outpatients 6-17 years of age (inclusive). Subjects with the diagnosis of Bipolar or Bipolar Spectrum Disorder and currently displaying manic, hypomanic, or mixed symptoms (with or without psychotic features), by DSM-IV, as manifested in clinical evaluation and confirmed by structured interview. Bipolar Spectrum Disorder (or sub- threshold bipolar disorder) is operationalized as having severe mood disturbance, which meets DSM-IV Criteria A for bipolar disorder but display fewer elements in Criteria B (only require 2 items for elation category and 3 for irritability). Subjects must score ≥ 20 on the YMRS. Subjects and their legal representative must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol. Subjects and their legal representative must be considered reliable reporters. Each subject and his/her authorized legal representative must understand the nature of the study. The subject's authorized legal representative must sign an informed consent document and the subject must sign an informed assent document (if ≥ 7 years old). Subject must be able to participate in mandatory blood draws. Subject must be able to swallow pills. Subjects with comorbid Oppositional Defiant Disorder (ODD), Conduct Disorder (CD), Obsessive-Compulsive Disorder (OCD), Pervasive Developmental Disorder (PDD), anxiety and depressive disorders will be allowed to participate in the study provided they do not meet for any of the exclusionary criteria. For concomitant therapy used to treat ADHD, subjects must have been on a stable dose of the medication for 1 month prior to study enrollment. The dose of the ADHD therapy will not change throughout the duration of the study. Exclusion Criteria: Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild. Serious, unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. Uncorrected hypothyroidism or hyperthyroidism. Non-febrile seizures without a clear and resolved etiology. DSM-IV substance (except nicotine or caffeine) dependence within past 6 months. Judged clinically to be at serious suicidal risk. Any other concomitant medication with primary central nervous system activity other than specified in the Concomitant Medication portion of the protocol. Current diagnosis of schizophrenia. Mental retardation (IQ < 75). Pregnant or nursing females. Known hypersensitivity to Invega® or similar formulations (paliperidone, risperidone). A non-responder or history of intolerance to Invega®, after treatment at adequate doses as determined by the clinician. Severe allergies or multiple adverse drug reactions. Subjects with a hematological disorder. Subjects with diabetes.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: paliperidone<br>* tablet, 3mgQAM - 6mgQAM, taken daily for 8 weeks<br>* Other names: Invega;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Symptoms Measured by Young Mania Rating Scale (YMRS) | The YMRS is an 11-item instrument used to assess the severity of mania in patients with a diagnosis of bipolar disorder. Four items are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven itemsare graded on a 0 to 4 scale. The maximum possible total score is 60 (worse outcome, severe symptoms), and the minimum possible total score is 0 (no symptoms). | Baseline and 8 weeks (or final study visit, if subjects completed the study before 8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Symptoms Measured by DSM-IV Mania Symptoms Checklist | A 13-item clinician-rated symptom checklist developed by Massachusetts General Hospital to measure symptoms of mania. Each item is given a rating for frequency (1=less than 4 days, 2=greater than or equal to 4 days, 3=daily) and intensity (1=mild, 2=moderate, 3=severe), which are combined to yield a composite severity score ranging from 0 (least severe) to 3 (most severe). The composite severity scores from all 13 items are summed to yield a total measure score, with a minimum score of 0 (least severe) and a maximum score of 39 (most severe). | Baseline and 8 weeks (or final study visit, if subjects completed the study before 8 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bipolar disorder, children, adolescents, Invega