Inositol and Omega-3 Fatty Acids in Pediatric Mania

NCT ID: NCT01396486

Last Updated: 2020-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-03
• Study Completion Date: 2019-04-11

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).

Conditions

Pediatric Bipolar Spectrum Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Omega-3/Placebo

Combination Omega-3 and Placebo treatment.

Group Type: ACTIVE_COMPARATOR

Omega-3

Intervention Type: DRUG

Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules.

Placebo/Inositol

Combination Placebo and Inositol treatment.

Group Type: ACTIVE_COMPARATOR

Inositol

Intervention Type: DRUG

Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.

Omega-3/Inositol

Combination Omega-3 and Inositol treatment.

Group Type: ACTIVE_COMPARATOR

Omega-3

Intervention Type: DRUG

Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules.

Inositol

Intervention Type: DRUG

Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.

Interventions

Omega-3

Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules.

Intervention Type: DRUG

Inositol

Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.

Intervention Type: DRUG

Other Intervention Names

ProOmega Junior

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Janet Wozniak, MD

Assistant Professor of Psychiatry at Harvard Medical School and at Massachusetts General Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Janet Wozniak, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26646031 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2009-P-001937

Identifier Type: -

Identifier Source: org_study_id