Dietary Intervention for Bipolar Disorder

May 9, 2019 updated by: Erika Saunders, Milton S. Hershey Medical Center

Targeted Alterations in n-3 and n-6 Fatty Acids for the Management of Mood Variability in the Maintenance Phase of Bipolar Disorder

Bipolar disorder (BD) is a chronic, often disabling illness, and many individuals remain symptomatic despite pharmacotherapy. Significant mood variability often persists throughout the lifespan and predicts relapse, leading to functional impairment. Metabolism of dietary essential polyunsaturated fatty acids has been shown to be upstream of the neuroinflammatory processes that may lead to neurotoxicity and chronicity of illness in BD. The investigators hypothesize that an intervention diet designed to alter intake of polyunsaturated fatty acids that augments mood stabilizing medications will reduce inflammation; and that the reduction of inflammation will reduce mood variability in bipolar disorder. After a two-the investigatorsek baseline-monitoring period, the investigators will randomize individuals with BD to an intervention or a control diet. Mood will be measured daily using a smartphone. Phase 2 will consist of 12 the investigatorseks of a less intense intervention. Follow-up will then be completed at 6, 9, and 12 months post-baseline to assess for recurrence of mood episodes. By maintaining a certain diet in addition to taking mood-stabilizing medication, researchers hope to see whether specific dietary plans have any bearing on mood variability.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators will conduct a 2-arm, parallel group, randomized, controlled 24-week dietary intervention to evaluate the therapeutic efficacy of two dietary interventions in patients with BD. After a two-week baseline-monitoring period, the investigators will randomize 84 patients with chronic BD to augment usual treatment with either an experimentally-altered omega-3, omega-6 intervention or a control diet with average US intakes of n-3 and n-6 fatty acids. Subjects in both groups will remain under the care of their physician for the full duration of the trial. During the first phase of the trial (12 weeks), the intervention will be intense, during the second phase (12 weeks), a less intense intervention will be delivered, and after the two phases of intervention there will be a 24-week follow-up period.

The study is designed to achieve the following specific aims and obtain support for the following hypotheses:

Specific Aim 1 (primary mood outcome): To compare the efficacy of the experimental dietary intervention to the control diet in reducing variability of mood symptoms and reducing general psychological distress.

Hypothesis 1: Compared to the control diet, the experimental intervention will produce significant improvement in (1a) variability of daily mood symptoms, energy, and impulsivity using a Visual Analogue Scale measured using ecological momentary analysis (1); and (1b) psychological distress and general functioning using the PROMIS-29.

Specific Aim 2 (secondary mood outcome): To compare the efficacy of the experimental dietary intervention to the control diet in reducing recurrence.

Hypothesis 2: Compared to the control diet, the experimental intervention will produce significant reduction in recurrence of mood episodes over a 12-month period. To adequately power this study for measurement of recurrence, the investigators would need a sample size 2-3 times what the investigators estimate for this study, therefore the primary mood outcome is not recurrence of episode, but is measurement of mood variability, which in turn predicts recurrence. The investigators will measure recurrence to gather data for future studies.

Specific Aim 3 (primary biochemical outcome): To evaluate whether the experimental dietary intervention can alter n-6 AA and its bioactive metabolites, n-3 DHA and its bioactive metabolites in patients with BD.

Hypothesis 3: Compared to the control diet, the experimental intervention will significantly (1a) alter n-6 AA and n-3 DHA in erythrocytes; and (1b) alter 17-hydroxy DHA and reduce PGE2 in plasma.

Exploratory Aims: In an exploratory manner, the investigators will also (1) compare the efficacy of the experimental dietary intervention to the control diet in improving headache-related clinical endpoints in the subset of BP patients with comorbid migraines; (2) test the effects of the dietary interventions on a wide array of bioactive derivatives of n-3 and n-6 fatty acids and other inflammatory mediators (e.g. cytokines, CRP); and (3) evaluate whether biochemical alterations in n-3 DHA, n-6 AA and their bioactive metabolites are related to clinical improvements (4) compare the efficacy of the experimental dietary intervention to the control diet in preventing recurrence of illness in follow-up; (5) store samples for exploratory biomarker analysis.

Study Type

Interventional

Enrollment (Actual)

83

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Milton S. Hershey Medical Center Clinical Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. BD - history of at least one manic or mixed episode
  2. Clinically significant hypomania or depression
  3. Current psychiatric treatment
  4. Over 18

Exclusion Criteria:

  1. Current hospitalization for BD
  2. Active substance dependence or eating disorder
  3. Active suicidal/homicidal ideation
  4. Pregnancy
  5. Active treatment for major medical illness
  6. History of specific food allergies such as, but not limited to, fish, gluten, dairy products
  7. Strong aversion to fish
  8. Any condition or attitude which, in the opinion of the PI, would prevent full cooperation and commitment to the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental diet
Altered n-6 and n-3 fatty acid intake.
Other: Experimental Diet
Altered n-6 (linoleic acid) and n-3 (eicosapentaenic acid (EPA) + docosahexaenoic acid (DHA)) diet.
Active Comparator: Comparator Diet
Diet standardized to usual n-6 and n-3 intake.
Other: Comparator Diet
Diet standardized to the usual American distribution of n-6 (7%) and n-3 EPA+DHA (150 mg per day).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mood variability outcome
Time Frame: Measured from the 2-week baseline period to the 12-week period of the phase 1 intervention
Each individual will be given a smartphone for fourteen weeks (2 weeks baseline plus 12 week phase 1 intervention) to measure facets of mood, sleep, and pain.
Measured from the 2-week baseline period to the 12-week period of the phase 1 intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence of mood episode
Time Frame: 1 year
Recurrence will be measured through phone interviews and review of medical records.
1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma levels of omega-6 fatty acids
Time Frame: Comparing from baseline to weeks 4, 8, 12
Group comparison of mean change from baseline in plasma levels of fatty acids, metabolites and lipidomics will be measured and analyzed in an exploratory fashion.
Comparing from baseline to weeks 4, 8, 12
Psychological distress and general functioning
Time Frame: Baseline & weeks 0, 4, 8, 12
Measured by PROMIS-29
Baseline & weeks 0, 4, 8, 12
Mood symptoms
Time Frame: Baseline & weeks 0, 4, 8, 12, 24, 48
Mood, sleep, psychosocial stress and pain questionnaires.
Baseline & weeks 0, 4, 8, 12, 24, 48
Plasma levels of omega-3 fatty acids
Time Frame: Baseline & weeks 4, 8, 12
Group comparison of mean change from baseline in plasma levels of fatty acids, metabolites and lipidomics will be measured and analyzed in an exploratory fashion.
Baseline & weeks 4, 8, 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Milton S. Hershey Medical Center

Collaborators

Stanley Medical Research Institute

Investigators

  • Principal Investigator: Erika Saunders, M.D, Milton S. Hershey Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Actual)

April 1, 2018

Study Completion (Actual)

April 1, 2019

Study Registration Dates

First Submitted

August 18, 2014

First Submitted That Met QC Criteria

October 20, 2014

First Posted (Estimate)

October 22, 2014

Study Record Updates

Last Update Posted (Actual)

May 10, 2019

Last Update Submitted That Met QC Criteria

May 9, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Stanley-13T-013

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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