Dietary Intervention for Bipolar Disorder

Sponsor

Milton S. Hershey Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT02272010

Collaborator

Stanley Medical Research Institute (Other)

Enrollment

Location

Arms

Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Other: Experimental Diet Other: Comparator Diet	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

83 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2014

Actual Primary Completion Date :

Apr 1, 2018

Actual Study Completion Date :

Apr 1, 2019

Arms and Interventions

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).

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).

Outcome Measures

Primary Outcome Measures

Mood variability outcome [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.

Secondary Outcome Measures

Recurrence of mood episode [1 year]
Recurrence will be measured through phone interviews and review of medical records.

Other Outcome Measures

Plasma levels of omega-6 fatty acids [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.
Psychological distress and general functioning [Baseline & weeks 0, 4, 8, 12]
Measured by PROMIS-29
Mood symptoms [Baseline & weeks 0, 4, 8, 12, 24, 48]
Mood, sleep, psychosocial stress and pain questionnaires.
Plasma levels of omega-3 fatty acids [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Milton S. Hershey Medical Center Clinical Research Center	Hershey	Pennsylvania	United States	17033

Sponsors and Collaborators

Milton S. Hershey Medical Center
Stanley Medical Research Institute

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Erika Saunders, Associate Professor of Psychiatry, Milton S. Hershey Medical Center

ClinicalTrials.gov Identifier:

NCT02272010

Other Study ID Numbers:

Stanley-13T-013

First Posted:

Oct 22, 2014

Last Update Posted:

May 10, 2019

Last Verified:

May 1, 2019

Additional relevant MeSH terms:

Bipolar Disorder

Study Results

No Results Posted as of May 10, 2019