Dietary Intervention for Bipolar Disorder
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional

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.
    

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.
    

Intervention name(s): Experimental Diet; Comparator Diet
Intervention type(s): Other; Other
Intervention description(s): Altered n-6 (linoleic acid) and n-3 (eicosapentaenic acid (EPA) + docosahexaenoic acid (DHA)) diet.; Diet standardized to the usual American distribution of n-6 (7%) and n-3 EPA+DHA (150 mg per day).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment