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Inositol and Omega-3 Fatty Acids in Pediatric Mania

Primary Purpose

Pediatric Bipolar Spectrum Disorders

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Omega-3

Inositol

About this trial

This is an interventional treatment trial for Pediatric Bipolar Spectrum Disorders focused on measuring Omega-3 Fatty Acids, Fish Oil, Inositol, Natural supplements, Bipolar Spectrum Disorders, Mania, Depression, Children

Eligibility Criteria

5 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female subjects, 5-12 years of age.
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).
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.
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.
Subjects must have an initial score on the YMRS total score of at least 20.
Subject must be able to swallow pills.
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:

Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild.
Serious or unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
History of bleeding diathesis, including those with von Willebrand disease.
Uncorrected hypothyroidism or hyperthyroidism.
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.
Severe allergies or multiple adverse drug reactions.
Failed 2 or more previous trials with anti-manic treatments including lithium, anticonvulsants and atypical antipsychotic medication.
Current or past history of seizures.
DSM-IV substance use, abuse or dependence (unlikely in ages 5-12).
Judged clinically to be at serious suicidal risk.
Current diagnosis of schizophrenia.
Current diagnosis of conduct disorder
Pregnancy (unlikely in ages 5-12).
YMRS Item #8 (Content) score of 8 ("delusions; hallucinations").
YMRS total score above 40.
Girls who have begun menstruating.
C-SSRS score ≥ 4.
IQ < 70.

Sites / Locations

Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Omega-3/Placebo

Placebo/Inositol

Omega-3/Inositol

Arm Description

Combination Omega-3 and Placebo treatment.

Combination Placebo and Inositol treatment.

Combination Omega-3 and Inositol treatment.

Outcomes

Primary Outcome Measures

Improvement in Mania Symptoms by Change in Young Mania Rating Scale (YMRS)

The Young Mania Rating Scale (YMRS) consists of 7 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe) and 4 items rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe).The YMRS score ranges from 0-60. Questions are asked about the last week. A higher score signifies more severe manic symptoms.

Improvement in Depression Symptoms by Children's Depression Rating Scale (CDRS)

The Children's Depression Rating Scale (CDRS) is a clinician-rated instrument with 17 items scored on a 1 to 5 or 1 to 7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. Scores of 20-30 suggest borderline depression. Scores of 40-60 indicate moderate depression.

Secondary Outcome Measures

Full Information

NCT ID

NCT01396486

First Posted

July 15, 2011

Last Updated

August 11, 2020

Sponsor

Massachusetts General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01396486

Brief Title

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

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

February 3, 2012 (Actual)

Primary Completion Date

April 11, 2019 (Actual)

Study Completion Date

April 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pediatric Bipolar Spectrum Disorders

Keywords

Omega-3 Fatty Acids, Fish Oil, Inositol, Natural supplements, Bipolar Spectrum Disorders, Mania, Depression, Children

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

69 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Omega-3/Placebo

Arm Type

Active Comparator

Arm Description

Combination Omega-3 and Placebo treatment.

Arm Title

Placebo/Inositol

Arm Type

Active Comparator

Arm Description

Combination Placebo and Inositol treatment.

Arm Title

Omega-3/Inositol

Arm Type

Active Comparator

Arm Description

Combination Omega-3 and Inositol treatment.

Intervention Type

Drug

Intervention Name(s)

Omega-3

Other Intervention Name(s)

ProOmega Junior

Intervention Description

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

Intervention Name(s)

Inositol

Intervention Description

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.

Primary Outcome Measure Information:

Title

Improvement in Mania Symptoms by Change in Young Mania Rating Scale (YMRS)

Description

Time Frame

Baseline to endpoint (12 weeks or last observation carried forward if dropped prior to week 12)

Title

Improvement in Depression Symptoms by Children's Depression Rating Scale (CDRS)

Description

Time Frame

Baseline to endpoint (12 weeks or last observation carried forward if dropped prior to week 12)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female subjects, 5-12 years of age. 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). 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. 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. Subjects must have an initial score on the YMRS total score of at least 20. Subject must be able to swallow pills. 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: Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild. Serious or unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. History of bleeding diathesis, including those with von Willebrand disease. Uncorrected hypothyroidism or hyperthyroidism. 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. Severe allergies or multiple adverse drug reactions. Failed 2 or more previous trials with anti-manic treatments including lithium, anticonvulsants and atypical antipsychotic medication. Current or past history of seizures. DSM-IV substance use, abuse or dependence (unlikely in ages 5-12). Judged clinically to be at serious suicidal risk. Current diagnosis of schizophrenia. Current diagnosis of conduct disorder Pregnancy (unlikely in ages 5-12). YMRS Item #8 (Content) score of 8 ("delusions; hallucinations"). YMRS total score above 40. Girls who have begun menstruating. C-SSRS score ≥ 4. IQ < 70.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janet Wozniak, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

26646031

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. Erratum In: J Clin Psychiatry. 2016 Sep;77(9):e1153.

Results Reference

derived

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Inositol and Omega-3 Fatty Acids in Pediatric Mania

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