Pediatric Bipolar Disorder
Conditions
Keywords
bipolar disorder, fish oil, aripiprazole, children
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
Interventions
DRUGAripiprazole
tablet, start at 2mg and increase/decrease each week, taken daily for 12 weeks
DIETARY_SUPPLEMENTfish oil
1600mg (4 capsules) daily for 12 weeks
DRUGPlacebo
Placebo
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subject, 6-17 years of age 2. 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) 3. 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 4. Subject and their legal representative must be considered reliable 5. 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 6. Subject must have an initial score on the Young-Mania Rating Scale (Y-MRS) of at least 20 7. Subject must be able to participate in mandatory blood draws 8. Subject must be able to swallow pills 9. 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 10. 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
1. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild 2. Serious, unstable illness including heptic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease 3. Uncorrected hypothyroidism or hyperthyroidism 4. 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. 5. Severe allergies or multiple adverse drug reactions. 6. Non-febrile seizures without a clear and resolved etiology 7. DSM-IV substance (except nicotine or caffeine) dependence within past 6 months 8. Judged clinically to be at serious suicidal risk 9. Any other concomitant medication with primarily central nervous system activity other than specified in the Concomitant Medication portion of the protocol. 10. Current diagnosis of schizophrenia 11. Pregnant or nursing females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole + Fish Oil treatment with aripiprazole + fish oil | 10 |
| Aripiprazole + Placebo treatment with aripiprazole + placebo | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Found ineligible | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Study drug expired | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Aripiprazole + Placebo | Aripiprazole + Fish Oil | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 11 years STANDARD_DEVIATION 3.71 | 10.8 years STANDARD_DEVIATION 3.65 | 10.9 years STANDARD_DEVIATION 3.58 |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 10 | 9 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Change in Bipolar Symptoms as Assessed by Young-Mania Rating Scale (YMRS)
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.
Time frame: weekly for 1st 6 weeks then biweekly
Population: 14 subjects came in for week 12 assessments - included in final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole + Fish Oil | Change in Bipolar Symptoms as Assessed by Young-Mania Rating Scale (YMRS) | 9.5 Units on a scale | Standard Deviation 7.78 |
| Aripiprazole + Placebo | Change in Bipolar Symptoms as Assessed by Young-Mania Rating Scale (YMRS) | 8.5 Units on a scale | Standard Deviation 7.4 |
Secondary
DSM-IV Mania Symptom Checklist
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.
Time frame: weekly for first 6 weeks then biweekly
Population: 14 subjects came in for week 12 assessments - included in final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole + Fish Oil | DSM-IV Mania Symptom Checklist | 5.25 units on a scale | Standard Deviation 5.23 |
| Aripiprazole + Placebo | DSM-IV Mania Symptom Checklist | 5 units on a scale | Standard Deviation 3.16 |