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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Ohio State University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
L. Eugene Arnold, The Ohio State University
ClinicalTrials.gov Identifier:
NCT01507753
First received: August 12, 2011
Last updated: October 28, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Bipolar Disorder
Dietary Supplement: Omega-3 Supplementation
Behavioral: Psychoeducational Psychotherapy (PEP)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Omega-3 Fatty Acids & Psychoeducational Psychotherapy for Childhood Bipolar Disorder- Not Otherwise Specified

Resource links provided by NLM:


Further study details as provided by Ohio State University:

Primary Outcome Measures:
  • Changes to K-SADS Mania Rating Scale (KMRS) [ Time Frame: Week prior to randomization and then weeks 2, 4, 6, 9, and 12 post-randomization ] [ Designated as safety issue: Yes ]
    This semi-structured interview contains 21 items that assess the severity of manic symptoms in children and adolescents. The KMRS shows high internal consistency (α = 0.94), sensitivity (0.87), and specificity (0.81) (Axelson et al., 2003). The KMRS will be administered at the assessment visits to determine worst lifetime and current (past two weeks) symptoms of mania.


Secondary Outcome Measures:
  • Changes to K-SADS Depression Rating Scale (KDRS) [ Time Frame: Week prior to randomization and then weeks 2, 4, 6, 9, and 12 post randomization ] [ Designated as safety issue: Yes ]
    Depressive symptom severity for worst past episode(s) and current episode (past two weeks) will be assessed using the KDRS at the assessment visits. The KDRS is a 12-item semi-structured interview with depression symptoms rated on a 6-point scale from none to severe. The KDRS has been shown to be a reliable measure of symptom severity.


Estimated Enrollment: 60
Study Start Date: September 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Supplement and No PEP
Will receive two capsules by mouth, two times daily matched for odor and appearance with the active intervention.
Experimental: 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.

Dietary Supplement: 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.
Other Name: Omega Brite
Behavioral: 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.
Other Name: IF-PEP
Experimental: 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.
Dietary Supplement: 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.
Other Name: Omega Brite
Experimental: 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.

Behavioral: 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.
Other Name: IF-PEP

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.

  Eligibility

Ages Eligible for Study:   7 Years to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01507753

Contacts
Contact: L. Eugene Arnold, MD, MEd 614-685-6708 l.arnold@osumc.edu
Contact: Kayden Z. Healy, BA 614-293-4908 kayden.healy@osumc.edu

Locations
United States, Ohio
Ohio State University Medical Center- Harding Hospital Recruiting
Columbus, Ohio, United States, 43210
Contact: L. Eugene Arnold, MD, MEd    614-685-6708    l.arnold@osumc.edu   
Principal Investigator: L. Eugene Arnold, MD, MEd         
Principal Investigator: Mary A Fristad, Phd         
Sponsors and Collaborators
L. Eugene Arnold
Investigators
Principal Investigator: L. Eugene Arnold, MD, MEd Ohio State University
Principal Investigator: Mary A Fristad, PhD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: L. Eugene Arnold, Principal Investigator, The Ohio State University
ClinicalTrials.gov Identifier: NCT01507753     History of Changes
Other Study ID Numbers: 2011H0104, 1 R34MH090148-01A1
Study First Received: August 12, 2011
Last Updated: October 28, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University:
childhood bipolar disorder

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on July 22, 2014