Omega-3 and Therapy Study for Childhood Bipolar Disorder- Not Otherwise Specified

NCT ID: NCT01507753

Last Updated: 2016-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2014-09-30

Brief Summary

Childhood bipolar disorder- not otherwise specified (BP-NOS) was originally considered to be a milder version of bipolar disorder (BD). Research now indicates that BP-NOS is a highly impairing condition. No pharmacologic treatment guidelines exist for BP-NOS. Available evidence-based pharmacotherapy guidelines are for BP1; efficacious medications are, unfortunately, associated with significant risk for adverse events (Kowatch et al, 2005; 2009). Previous research on diet and nutrition suggests that omega-3 (Ω3) fatty acids have a beneficial effect on mood, which might provide either a primary or adjunctive treatment with a more favorable risk:benefit ratio for children suffering from BP-NOS than currently available pharmacologic interventions. Psychoeducational psychotherapy (PEP) also has shown promise in treating bipolar spectrum disorders in children aged 8-12 (Fristad, 2006; Fristad, Verducci, Walters, & Young, 2009); its efficacy in treating BP-NOS specifically has not been determined.

The current study compares Ω3, PEP, and their combination to a placebo supplement and active monitoring (AM) in a 12-week trial of 60 children with BP-NOS (15 each with Ω3, Ω3 plus PEP, PEP, and placebo, all with active monitoring). Primary goals are to determine: 1) feasibility of a) recruiting 60 participants in 2 years; b) participant retention over a 12-week trial; and 2) placebo-controlled effect sizes for Ω3, PEP, and combination treatment on manic and depressive symptoms. Secondary goals are to explore response curves over time, mediators and moderators, treatment response across a broad array of outcome variables, adherence to treatment, impact on physiologic parameters often worsened by mood stabilizing medications, and experience of side-effects in participants receiving Ω3 and/or PEP. Comparisons of results to a parallel study of children with depression with identical design will maximize knowledge gained. This pilot study of Ω3, PEP, and combined treatment will provide evidence about whether a larger trial is feasible and justified.

Detailed Description

Research indicates BP-NOS is a highly impairing condition comparable to the other bipolar spectrum disorders. Considerable gains have been made recently in understanding BP-NOS, in large part by research utilizing clear operational definitions for BP-NOS. However, clinical trials have focused on youth with Bipolar Disorder- Type I (BP1). No clinical guidelines exist for the treatment of BP-NOS.

No pharmacologic treatment guidelines exist for BP-NOS. Available evidence-based pharmacotherapy guidelines are for BP1 and are associated with significant risk for adverse events. Additionally, while anti-manic agents have been identified, no study has demonstrated an effective anti-depressant agent for youth with bipolar depression. A review of weight gain and metabolic side effects of mood stabilizers and antipsychotic medications in 19 studies of pediatric bipolar patients found significant and clinically relevant weight increases in 18 trials. Clinical trials of depression and bipolar disorders in children and adolescents show approximately 20%-25% of participants dropped out of short-term psychotropic medication treatment trials. Additionally, a recent study of an anticonvulsant mood stabilizer in children failed to show any superiority to placebo.

Previous research on diet and nutrition suggests that omega-3 (Ω3) fatty acids have a beneficial effect on mood with little evidence of negative side-effects or deleterious drug interactions, suggesting Ω3 might function as either a primary or adjunctive treatment with a more favorable risk-benefit ratio for children suffering from BP than currently available pharmacologic interventions.Psychoeducational psychotherapy (PEP) also has shown promise in treating bipolar spectrum disorders in children aged 8-12 its efficacy in treating BP-NOS specifically has not been determined.

The current study compares Ω3, PEP, and their combination to a placebo supplement, all with active monitoring (AM) in a 12-week trial of 60 children with BP-NOS (15 each with Ω3, Ω3 plus PEP, PEP, and placebo. Primary goals are to determine: 1) feasibility of a) recruiting 60 participants in 2 years; b) participant retention over a 12-week trial; and 2) placebo-controlled effect sizes for Ω3, PEP, and combination treatment on manic and depressive symptoms. Secondary goals are to explore response curves over time, mediators and moderators, treatment response across a broad array of outcome variables, adherence to treatment, impact on physiologic parameters often worsened by mood stabilizing medications, and experience of side-effects in participants receiving Ω3 and/or PEP. Comparisons of results to a parallel study of children with depression with identical design will maximize knowledge gained. This pilot study of Ω3, PEP, and combined treatment will provide evidence about whether a larger trial is feasible and justified.

Conditions

Bipolar Disorder

Study Design

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

Study Groups

Placebo Supplement and No PEP

Will receive two capsules by mouth, two times daily matched for odor and appearance with the active intervention.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

The placebo group will receive active monitoring (no IF-PEP) and two capsules two times daily matched for odor and appearance with the active intervention.

Omega-3 and PEP

Omega-3 Supplementation will receive 1000 mg Ω3 (two 500 mg capsules, each containing 350 mg EPA: 50 mg DHA; 100 other Ω3)by mouth, two times daily.

Psychoeducational Psychotherapy (PEP)Therapy sessions occur twice a week for up to 24 sessions of manualized treatment.

Group Type: EXPERIMENTAL

Omega-3 Supplementation

Intervention Type: DRUG

The Ω3 group will receive 1000 mg Ω3 (two 500 mg capsules, each containing 350 mg EPA: 50 mg DHA; 100 other Ω3) two times daily for a total daily dose of 2000 mg Ω3 (1400 mg EPA: 200 mg DHA; 400 other Ω3). The placebo group will receive two capsules two times daily matched for odor and appearance with the active intervention.

Psychoeducational Psychotherapy (PEP)

Intervention Type: BEHAVIORAL

Therapy sessions occur twice a week for up to 24 sessions of manualized treatment. The importance of separating symptoms from the individual is emphasized. The family is offered support, validation, and recognition for their own difficult experiences in living with the child's mood disorder. Family members are taught that patients are particularly vulnerable to stress and tension; thus, therapists work with families to reduce the level of stress and tension in their homes. Improvement of communication, problem solving and coping strategies can lead to restoration of hope for recovery and decrease family dysfunction. Goals include strengthening the parent-child bond and helping children and parents feel competent to manage depression now and in future recurrences.

Omega-3 and No PEP

Omega-3 Supplementation will receive 1000 mg Ω3 (two 500 mg capsules, each containing 350 mg EPA: 50 mg DHA; 100 other Ω3)by mouth, two times daily.

Group Type: EXPERIMENTAL

Omega-3 Supplementation

Intervention Type: DRUG

The Ω3 group will receive 1000 mg Ω3 (two 500 mg capsules, each containing 350 mg EPA: 50 mg DHA; 100 other Ω3) two times daily for a total daily dose of 2000 mg Ω3 (1400 mg EPA: 200 mg DHA; 400 other Ω3). The placebo group will receive two capsules two times daily matched for odor and appearance with the active intervention.

Placebo Supplement and PEP

Placebo Supplement will receive two capsules by mouth, two times daily matched for odor and appearance with the active intervention.

Psychoeducational Psychotherapy (PEP)Therapy sessions occur twice a week for up to 24 sessions of manualized treatment.

Group Type: EXPERIMENTAL

Psychoeducational Psychotherapy (PEP)

Intervention Type: BEHAVIORAL

Therapy sessions occur twice a week for up to 24 sessions of manualized treatment. The importance of separating symptoms from the individual is emphasized. The family is offered support, validation, and recognition for their own difficult experiences in living with the child's mood disorder. Family members are taught that patients are particularly vulnerable to stress and tension; thus, therapists work with families to reduce the level of stress and tension in their homes. Improvement of communication, problem solving and coping strategies can lead to restoration of hope for recovery and decrease family dysfunction. Goals include strengthening the parent-child bond and helping children and parents feel competent to manage depression now and in future recurrences.

Interventions

Omega-3 Supplementation

The Ω3 group will receive 1000 mg Ω3 (two 500 mg capsules, each containing 350 mg EPA: 50 mg DHA; 100 other Ω3) two times daily for a total daily dose of 2000 mg Ω3 (1400 mg EPA: 200 mg DHA; 400 other Ω3). The placebo group will receive two capsules two times daily matched for odor and appearance with the active intervention.

Intervention Type: DRUG

Psychoeducational Psychotherapy (PEP)

Therapy sessions occur twice a week for up to 24 sessions of manualized treatment. The importance of separating symptoms from the individual is emphasized. The family is offered support, validation, and recognition for their own difficult experiences in living with the child's mood disorder. Family members are taught that patients are particularly vulnerable to stress and tension; thus, therapists work with families to reduce the level of stress and tension in their homes. Improvement of communication, problem solving and coping strategies can lead to restoration of hope for recovery and decrease family dysfunction. Goals include strengthening the parent-child bond and helping children and parents feel competent to manage depression now and in future recurrences.

Intervention Type: BEHAVIORAL

Placebo

The placebo group will receive active monitoring (no IF-PEP) and two capsules two times daily matched for odor and appearance with the active intervention.

Intervention Type: OTHER

Other Intervention Names

Omega Brite; IF-PEP; Pbo

Eligibility Criteria

Inclusion Criteria

• Aged 7-14 years (boys and girls)
• Has a diagnosis of BP-NOS according to the LAMS definition. Criteria as follows:
• Clinically significant bipolar symptoms that do not meet DSM IV TR criteria for bipolar disorder I or bipolar disorder II
• Elated mood plus 2 or more associated symptoms from DSM IV TR or irritable mood plus 3 or more symptoms
• A change in functioning, and a minimum duration of 4 hours within a 24-hour period and at least 4 cumulative lifetime days meeting criteria
• Full scale IQ ≥ 70
• Child and one parent or other caregiver must be able to complete all assessment
• Child must be able to swallow capsules (training in swallowing will be offered)
• Parent and child must be willing to have blood drawn from child at two study assessments.

Exclusion Criteria

• Major medical disorders (eg diabetes, epilepsy, metabolic disorder)
• Inability to communicate in English
• Lack of access via phone
• Autism
• Schizophrenia, or other psychotic states warranting anti-psychotic medication
• Active suicidal concern (e.g., "I want to kill myself", a plan for suicide, or an attempt in the past month; however, passive suicidal ideation, such as "I wish I were dead" would not exclude)
• Three or more symptoms rated as "marked" or "severe" on the KDRS or KMRS
• Concurrent mental health intervention (pharmacotherapy and/or psychotherapy) in the past month.

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

L. Eugene Arnold

OTHER

Sponsor Role: lead

Responsible Party

L. Eugene Arnold

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

L. Eugene Arnold, MD, MEd

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Mary A Fristad, PhD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University Medical Center- Harding Hospital

Columbus, Ohio, United States

Countries

United States

References

Vesco AT, Young AS, Arnold LE, Fristad MA. Omega-3 supplementation associated with improved parent-rated executive function in youth with mood disorders: secondary analyses of the omega 3 and therapy (OATS) trials. J Child Psychol Psychiatry. 2018 Jun;59(6):628-636. doi: 10.1111/jcpp.12830. Epub 2017 Oct 24.

Reference Type: DERIVED

PMID: 29063592 (View on PubMed)

Christian LM, Young AS, Mitchell AM, Belury MA, Gracious BL, Arnold LE, Fristad MA. Body weight affects omega-3 polyunsaturated fatty acid (PUFA) accumulation in youth following supplementation in post-hoc analyses of a randomized controlled trial. PLoS One. 2017 Apr 5;12(4):e0173087. doi: 10.1371/journal.pone.0173087. eCollection 2017.

Reference Type: DERIVED

PMID: 28379964 (View on PubMed)

Fristad MA, Young AS, Vesco AT, Nader ES, Healy KZ, Gardner W, Wolfson HL, Arnold LE. A Randomized Controlled Trial of Individual Family Psychoeducational Psychotherapy and Omega-3 Fatty Acids in Youth with Subsyndromal Bipolar Disorder. J Child Adolesc Psychopharmacol. 2015 Dec;25(10):764-74. doi: 10.1089/cap.2015.0132.

Reference Type: DERIVED

PMID: 26682997 (View on PubMed)

Other Identifiers

1R34MH090148-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2011H0104

Identifier Type: -

Identifier Source: org_study_id