Clinical trial NCT01396486: Inositol and Omega-3 Fatty Acids in Pediatric Mania
Official title: A Randomized Controlled Trial of Inositol and Omega-3 Fatty Acids in Pediatric Mania
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pediatric Bipolar Spectrum Disorders
Keywords: Omega-3 Fatty Acids
Fish Oil
Inositol
Natural supplements
Bipolar Spectrum Disorders
Mania
Depression
Children
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2011-07-18
Enrollment: 69
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to a) evaluate the efficacy of omega-3 fatty acids versus inositol in the treatment of pediatric bipolar disorder, b) evaluate the efficacy of omega-3 fatty acid plus inositol in the treatment of pediatric bipolar disorder, and c) assess the side effect profile of omega-3 fatty acids plus inositol. This study will be a 12-week trial with children ages 5-12 years old with bipolar spectrum disorders.

Detailed description: The investigators propose to conduct a randomized, double blind, controlled trial that will evaluate effectiveness and tolerability of omega-3 fatty acids and inositol used alone and in combination. The investigators plan to decrease the variability in the population under study by limiting the age range to 5-12 years and excluding cases with significant, untreated, comorbidity. The cognitive effects/side effects with a neuropsychological battery pre and post treatment will be measured. Subjects with a history of failing treatment with two or more conventional treatments will be excluded.

This will be a 12-week, double-blind, randomized clinical trial study to compare efficacy and tolerability of the natural treatments omega-3 fatty acids and inositol used in combination in the treatment of bipolar spectrum disorders in children and adolescents (ages 5-12). Subjects will be randomized in double blind fashion to one of three arms: omega-3 fatty acids, inositol or the combined treatment. Further, the proposed study will include measures of cognition prior to starting study medication and at endpoint. The investigators will minimize the variability of the population under study by limiting the age range to 5-12 years, minimizing untreated or clinically significant comorbidity and excluding subjects who have already failed treatment with 2 or more anti-manic agents. Subjects will include youth ages 5-12 years with a bipolar spectrum disorder (type I, II, or NOS), mixed, manic, or hypomanic state, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (American Psychiatric Association, 2000) (DSM-IV), randomized to 3 treatment arms: 1) treatment with omega-3 fatty acids (N=20); 2) treatment with inositol (N=20); 3) treatment with the combination of inositol and omega-3 fatty acids (N=20).

Eligibility criteria: Inclusion Criteria:

1. Male or female subjects, 5-12 years of age.
2. Subjects must have a DSM-IV diagnosis of a bipolar spectrum disorder (type I, II, or Not Otherwise Specified (NOS)), and currently displaying mixed, manic, or hypomanic symptoms (without psychotic features) according to the DSM-IV based on clinical assessment and confirmed with structured diagnostic interview (Schedule of Affective Disorders and Schizophrenia for School-Age Children - Epidemiological Version (K-SADS-E)) (Orvaschel, 1994).
3. 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.
4. Subjects and their legal representative must be considered reliable.
5. 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.
6. Subjects must have an initial score on the YMRS total score of at least 20.
7. Subject must be able to swallow pills.
8. Subjects with ADHD and ODD will be allowed to participate in the study provided that the impairment associated with these disorders is of mild or moderate severity (not severe) and milder in severity relative to the impairment of the bipolar disorder, according to clinician evaluation. Subjects with comorbid anxiety disorders will be allowed to participate provided that the impairment associated with the anxiety is of minimal severity, according to clinician evaluation. Subjects with comorbid CD will be excluded.

Exclusion Criteria:

1. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild.
2. Serious or unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
3. History of bleeding diathesis, including those with von Willebrand disease.
4. Uncorrected hypothyroidism or hyperthyroidism.
5. History of sensitivity to omega-3 fatty acids or inositol. A non-responder or history of intolerance to omega-3 fatty acid or inositol, after 2 months of treatment at adequate doses as determined by the clinician.
6. Severe allergies or multiple adverse drug reactions.
7. Failed 2 or more previous trials with anti-manic treatments including lithium, anticonvulsants and atypical antipsychotic medication.
8. Current or past history of seizures.
9. DSM-IV substance use, abuse or dependence (unlikely in ages 5-12).
10. Judged clinically to be at serious suicidal risk.
11. Current diagnosis of schizophrenia.
12. Current diagnosis of conduct disorder
13. Pregnancy (unlikely in ages 5-12).
14. YMRS Item #8 (Content) score of 8 ("delusions; hallucinations").
15. YMRS total score above 40.
16. Girls who have begun menstruating.
17. C-SSRS score ≥ 4.
18. IQ \< 70.

Primary outcomes:
measure: Improvement in Mania Symptoms by Change in Young Mania Rating Scale (YMRS)
timeFrame: Baseline to endpoint (12 weeks or last observation carried forward if dropped prior to week 12)
measure: Improvement in Depression Symptoms by Children's Depression Rating Scale (CDRS)
timeFrame: Baseline to endpoint (12 weeks or last observation carried forward if dropped prior to week 12)
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Janet Wozniak, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wozniak J, Faraone SV, Chan J, Tarko L, Hernandez M, Davis J, Woodworth KY, Biederman J. A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study. J Clin Psychiatry. 2015 Nov;76(11):1548-55. doi: 10.4088/JCP.14m09267.