Omega-3 Fatty Acid Adjunctive to Open-Label Aripiprazole for the Treatment of Bipolar Disorder in Children and Adolescents

Phase 4

Terminated

Conditions: Pediatric Bipolar Disorder

Interventions: Drug: Aripiprazole
Dietary Supplement: fish oil
Drug: Placebo

Registration Number: NCT00592683

Lead Sponsor: Massachusetts General Hospital

Brief Summary: This will be a 12 week, double blind study of omega-3 fatty acids vs. placebo adjunctive to open-label aripiprazole treatment in children and adolescents (ages 6-17) who meet DSM-IV criteria for bipolar disorder (BPD) (currently manic or mixed). Specific hypotheses are as follows:

Hypothesis 1: Omega-3 fatty acids will be well-tolerated and efficacious in the treatment of children and adolescents with BPD

Hypothesis 2: The total dose of aripiprazole will be lower in those subjects receiving active omega-3 treatment

Detailed Description: Initial clinical evidence suggests that the omega-3 fatty acids EPA (eicosapentaenoic acid) and/or DHA (docosahexaenoic acid) may play a therapeutic role in the management of mood disorders. EPA is an essential fatty acid, which can be metabolized to DHA and is a component of the human diet if fish is consumed. Aripiprazole is a novel second general antipsychotic that seems to function as a partial agonist at the dopamine D2 and serotonin 5-HT 1A receptors as well as an antagonist at the serotonin 5-HT 2A receptor. Since it has a favorable adverse event profile in adults, it is an attractive choice for the treatment of youth with bipolar disorder if proven efficacious. Although pilot research showed that omega-3 fatty acids monotherapy treatment resulted in improvement of manic symptoms, the improvement is less dramatic than that observed in trials of antipsychotics. We will test the safety and efficacy of omega-3 fatty acids versus placebo as an adjunctive treatment to open-label aripiprazole in children and adolescents with bipolar disorder.

The proposed study includes 1) the use of a 12-week design to document the response rate 2) careful assessment of safety and tolerability

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Male or female subject, 6-17 years of age
Subject has a DSM-IV diagnosis of bipolar I, bipolar II, or bipolar spectrum disorder and currently displaying manic, hypomanic, or mixed symptoms (with or without psychotic features)
Subject and their legal representative 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
Subject and their legal representative must be considered reliable
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
Subject must have an initial score on the Young-Mania Rating Scale (Y-MRS) of at least 20
Subject must be able to participate in mandatory blood draws
Subject must be able to swallow pills
Subjects with comorbid Attention Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), Conduct Disorder (CD), Obsessive Compulsive Disorder (OCD), Pervasive Developmental Disorders (PDD), anxiety and depressive disorders will be allowed to participate in the study provided they do not meet for any of exclusionary criteria
For concomitant therapy used to treat ADHD, subject must have been on a stable dose of the medication for 1 month prior to study enrollment. The dose of the ADHD therapy may 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 heptic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease
Uncorrected hypothyroidism or hyperthyroidism
History of sensitivity to omega-3 fatty acids. A non-responder or history of intolerance to omega-3 fatty acid, after treatment at adequate doses as determined by the clinician.
Severe allergies or multiple adverse drug reactions.
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 primarily central nervous system activity other than specified in the Concomitant Medication portion of the protocol.
Current diagnosis of schizophrenia
Pregnant or nursing females

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Aripiprazole plus Fish Oil	fish oil	Subjects administered aripiprazole and randomized to receive fish oil
Aripiprazole plus Placebo	Placebo	Subjects administered aripiprazole and randomized to receive placebo
Aripiprazole plus Fish Oil	Aripiprazole	Subjects administered aripiprazole and randomized to receive fish oil
Aripiprazole plus Placebo	Aripiprazole	Subjects administered aripiprazole and randomized to receive placebo

Primary Outcome Measures

Name	Time	Method
Change in Bipolar Symptoms as Assessed by Young-Mania Rating Scale (YMRS)	weekly for 1st 6 weeks then biweekly	The YMRS is used to evaluate symptoms of mania in children and adolescents. Items are rated from 0-4 or 0-8, with higher scores indicating greater severity. The minimum total score (least severe) is 0, and the maximum total score (most severe) is 60.

Secondary Outcome Measures

Name	Time	Method
DSM-IV Mania Symptom Checklist	weekly for first 6 weeks then biweekly	The DSM-IV Mania Symptom Checklist is used to evaluate symptoms of mania. Item scores range from 0-3, with larger scores indicating greater severity. With 33 items, the maximum (most severe) score possible is 99, with the minimum (least severe) score possible being 0.