Healthy Lifestyles for Bipolar Disorder (HL)

Time-restricted Eating vs. Mediterranean Diet as Adjunctive Interventions for Bipolar Disorder

The goal of this clinical trial is to compare the effects of two different healthy lifestyles on outcomes for those with bipolar disorder. The goals are to understand the acceptability of time-restricted eating and the mediterranean diet for those who are already receiving medication treatment for bipolar disorder, and to consider how these two food plans predict changes in manic symptoms, depressive symptoms, and Quality of Life. Participants will complete daily measures of eating, sleep and mood for two weeks, and then will be assigned to follow one of the two food plans for eight weeks. The investigators will measure symptoms and Quality of Life at baseline and during and after the food plan.

Study Overview

• Status: Recruiting
• Conditions: Time Restricted Eating; Diet, Mediterranean
• Intervention / Treatment: Behavioral: Time restricted eating; Behavioral: Mediterranean diet

Detailed Description

The investigators will conduct a randomized controlled trial (RCT) to examine the effects of time-restricted eating as compared to the mediterranean diet. In time-restricted eating (TRE), participants will be asked to limit their food intake to a period of 10 hours per day. In the mediterranean diet, participants will be asked to follow a food plan that emphasizes vegetables, fruit, whole grains, and olive oil as central dietary components. The investigators aim to test both food plans as additions to standard medication approaches in bipolar disorder. Participants who are receiving medical treatment for bipolar disorder and who report at least some sleep or circadian problems will complete baseline measures and then will be randomly assigned to TRE or the mediterranean diet for 8 weeks, and then will complete measures of symptoms, Quality of Life, and possible treatment mechanisms at the end of treatment and at 3, 6 and 12 months after the intervention. If successful, this work will provide a novel, easily implemented and highly acceptable intervention for BD.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sheri L Johnson, PhD; Phone Number: (510) 519-4305; Email: calmprogram@berkeley.edu
• Study Contact Backup: Name: Nandini Rajgopal, BS; Phone Number: (510) 519-4305; Email: calmprogram@berkeley.edu

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94720
      • Recruiting
      • University of California
      • Contact: Sheri L Johnson; Phone Number: 415-347-6755; Email: sljohnson@berkeley.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• meets diagnostic criteria for bipolar I disorder or bipolar II disorder (but not cyclothymia, BD Not otherwise specified or BD due to another medical condition)

• current sleep (insomnia, hypersomnolence) or circadian sleep-wake (delayed phase, advanced phase, irregular sleep-wake, non-24-hour sleep-wake-type) concerns indicated by endorsement of at least some sleep or circadian-related impairment across the screening self-reports or interview

  • Living in an English-speaking country (and one that we have expertise in research procedures and diet)
  • Has been speaking English for at least 10 years, speaks English in the home, or certifies that they are able to understand English well for the study and demonstrates this during the screening interview.
  • Receiving medical care for BD (referrals will be provided for those who would like to begin care)
  • Mood-stabilizing medication regimens stable for at least one month
  • < 5 kg weight change in the past 3 months
  • Currently eating ≥ 12 hours per day at least twice per week
  • Able to operate the camera function and respond to web-based surveys by phone (loaner phones will be provided as needed)
  • Not engaged in current shift work or have other responsibilities such as providing care that would chronically disrupt their sleep (i.e., > 3 h between 22:00 and 05:00 h for at least 1 day/week)
  • Able to complete 7 days of dietary logs adequately (e.g., at least 2 entries per day, covering at least a 5-hour eating window) during the baseline period
  • Able to complete screening and baseline questionnaires adequately (e.g., not failing more than 1 attention check item with instructed responding; responding to standard multiple-choice items in a mean of < 2 seconds per item). Where individuals respond to more than 14 items in a row with the same response, we will manually review for possible invalidity.

Exclusion criteria include the following:

• Current episode of depression, hypomania or mania, or psychosis (assessed by the aDiagnostic Interview for Anxiety, Mood, and Obsessive-compulsive and Related Neuropsychiatric Disorders; DIAMOND), Participants with acute mood disorder episodes will be encouraged to seek treatment and to consider the study when symptoms have remitted.
• Eating disorder diagnosis (by self-report of treatment or diagnosis at any point during their life, Short Eating Disorder Examination Questionnaire (EDE-QS) scores above clinical concern thresholds for eating disorders, or DIAMOND interview of symptoms during adulthood)
• Past 3-month alcohol use disorder or substance use disorder (assessed by DIAMOND)
• Active suicidal ideation coupled with plan, intent or attempt history as assessed by Columbia Suicide Severity Rating Scale
• Conditions that would interfere with ability to take part in the intervention , including pregnancy, breastfeeding, uncorrected hypo or hyperthyroidism, gastrointestinal conditions impairing nutrient absorption,
• Medical conditions such as HIV, AIDS, lupus, or multiple sclerosis that could confound the assessment of mania or other measures
• Medications contraindicated for fasting: clozapine, glucose-lowering medications, diabetes-related injections, medications requiring food early morning or late evening, corticosteroids; medications such as semaglutide will not be an exclusion criteria
• Cognitive deficits as noted during the initial interview or as indicated by low performance on the Short Orientation Memory Concentration Test (< 20 on the weighted score).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Time Restricted Eating (TRE) for 8 weeks; Participants will receive an intro to TRE and then throughout 8 weeks they will receive brief online psychoeducation several times per week with optional weekly coaching sessions. TRE involves restricting the window of eating to 10 hours/ day, most typically by avoiding eating in the first 1-2 hours after awakening and in the 2-4 before sleep. Those with an eating window > 14 hours will be asked to restrict their eating to 12 hours in the first week, then 10 hours in week 2. To select the period, investigators will ask Ss to review baseline logs to consider sleep, eating, family meals and social commitment schedules, and any special energy demands, such as exercise. During the eating window, no restrictions are placed on the type or quantity of food consumed. The investigators will instruct participants to follow their habitual diet within their 10-hour eating window and to aim to consume the same number of calories per day as they did at baseline.	Behavioral: Time restricted eating; Limiting food intake to 10 hours per day; Other Names: intermittent fasting
Active Comparator: Mediterranean diet for 8 weeks; Participants will receive a several page introduction to the mediterranean diet, and then will receive support throughout the 8 week intervention to follow this food plan, including brief online psychoeducation that will be sent several times per week, and optional weekly coaching sessions. The mediterranean diet is a plan for healthy eating based on how people eat in the mediterranean region. Individuals will be encouraged to consume vegetables (6 servings/day), fruits (2-4 servings/day), whole grains (daily), legumes (3-4 times per week), nuts (.5 oz per day), and oily fish (2 servings/week). Participants will be encouraged to choose lean meats and other sources of protein over red meat and processed meats. Sweets, refined cereals, alcohol, and wine or alcohol will be labelled as extras, and participants will be encouraged to limit consumption of extras.	Behavioral: Mediterranean diet; Dietary advice designed to improve consumption of vegetables, fruits, whole grains, and the use of olive oil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to time-restricted eating	Adherence will be scored based on the time of their first and final calorie consumption each day during the 8 week intervention. The investigators will select entries from the time interval that contains 95% of intake events. Following standards in other US and European studies of TRE, the investigators will focus on days in which participants adequately logged (e.g., entered at least two intake events, covering at least a 5 hour window), and will calculate the percentage of days in which individuals met the eating window goal. High adherence will be defined as meeting this standard on at least 78% of days logged. As supplemental data, the investigators will report the percentage of days logged, and the percentage of days in which individuals logged adequately and followed the planned window.	Average number of daily food logs showing adherence across the 8-week intervention
Mania	Decline in Young Mania Rating Scale (YMRS) total scores, completed by a blind rater	Lower YMRS at the end of intervention (10 weeks) as compared to baseline
Depression	Decline in Montgomery Asberg Depression Scale (MADRS) total scores, completed by a blind rater	Lower MADRS at the end of intervention (10 weeks) as compared to baseline
Mania at follow-up	Sustained lower YMRS scores across follow-up	YMRS scores will be lower at 3, 6, 12 month post-intervention follow-ups as compared to baseline
Depression at follow-up	Sustained lower MADRS scores across follow-up	MADRS scores will be lower at 3, 6, 12 month post-intervention follow-ups as compared to baseline
Acceptability	Participant self-ratings of the acceptability of the intervention: The primary index of acceptability will be the percentage of individuals who endorse that they agree or strongly agree that they would recommend the food plan to a friend. This single item has been used in previous trials of bipolar disorder. Higher agreement will be considered a positive outcome.	immediately post-treatment (10 weeks after enrollment)
Adherence to Mediterranean Diet	Adherence will be scored based on a Food Frequency Questionnaire that we developed for this study. We will score this using the Adherence to the Mediterranean Diet scoring system (AMed), which provides up to 9 points based on above-median consumption of beneficial foods (e.g., fruits and vegetables) and below median consumption of "extras" such as alcohol. Higher scores reflect better adherence to the mediterranean diet.	Average number of food logs showing adherence at or above the median for 2 days at the mid-point of treatment (week 6) and at the end of treatment (week 10)
Self-rated Quality of Life (QOL)	Higher scores on the self-rated Brief Quality of Life in Bipolar Disorder (QoL.BD) at 1.5-months post intervention as compared to baseline	Scores at 1.5-months post-intervention (16 weeks after study entry) as compared to baseline
QOL at follow-up	Sustained higher Brief QOL.BD scores	Brief QOL.BD scores will be higher at 6- and 12-month post-intervention follow-ups as compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-rated mania	Lower Patient Health Questionnaire (PHQ) Mania scores at post-intervention (10 weeks) and at 1.5, 3, 6, and 12 month follow-ups post-intervention	at post-intervention (10 weeks) and at 1.5, 3, 6, and 12 month follow-ups post-intervention, as compared to baseline
Self-rated depression	Lower Patient Health Questionnaire (PHQ) Depression scores at post-intervention (10 weeks) and at 1.5, 3, 6, and 12 month follow-ups post-intervention	at post-intervention (10 weeks) and at 1.5, 3, 6, and 12 month follow-ups post-intervention, as compared to baseline
Sleep hygiene behaviors	Lower scores on the Sleep Household Environment and In-Bed Behaviors at end-of-treatment (10 weeks) as compared to baseline	post-intervention (10 weeks) as compared to baseline
Weekly change in mania severity	Lower Longitudinal Interval Follow-up Evaluation (LIFE) weekly Mania scores post-treatment as compared to those at baseline. The investigators will administer the LIFE interview at 3, 6, and 12-months after the intervention, and interviewers will record a mania severity rating for each week, to cover the time from the end of intervention until one year after the intervention ends.	Weekly scores from the end of the intervention through one-year post-intervention follow-up
Sleep disturbance and sleep impairment	Lower scores on the Patient Outcomes Reporting Information System (PROMIS) sleep disturbance and sleep impairment scores at post-treatment (10 weeks) as compared to baseline	post-treatment (10 weeks) as compared to baseline
Sleep mid-point variability (Munich Chronotype Questionnaire; MCTQ)	MCTQ scores will show a smaller proportion of individuals with either early or delayed chronotype (as reflected in standard scoring for the MCTQ) at post-treatment as compared to baseline	post-treatment (10 weeks) as compared to baseline
Regularity of daily routines (Brief Social Rhythm Questionnaire)	Lower Brief Social Rhythm Questionnaire scores (less irregularity) at post-treatment as compared to baseline	post-treatment (10 weeks) as compared to baseline
Daily emotional lability as assessed using ecological momentary assessment	Lower mean square of successive difference of negative affect scores within derived from the ecological momentary assessments at the mid-point of treatment (6 weeks) as compared to baseline. Participants will be asked to complete negative affect ratings several times per day for 8 days, at the baseline and mid-point of treatment. The investigators will calculate scores to examine the degree of negative affect variability for each day, and then take the average across 8 days at baseline and at treatment mid-point.	mid-point of treatment (6 weeks post study entry) as compared to baseline

Collaborators and Investigators

• Sponsor: University of California, Berkeley
• Collaborators: University of British Columbia; University College, London; Wellcome Trust; Salk Institute for Biological Studies; Deakin University; Swinburne University of Technology
• Investigators: Principal Investigator: Sheri L Johnson, PhD, University of California, Berkeley

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2024
• Primary Completion (Estimated): December 28, 2028
• Study Completion (Estimated): February 28, 2029

Study Registration Dates

• First Submitted: December 18, 2023
• First Submitted That Met QC Criteria: December 18, 2023
• First Posted (Actual): January 3, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: sleep; bipolar disorder; circadian rhythm
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Bipolar Disorder
• Other Study ID Numbers: Healthy Lifestyles 01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Measures, data, and analysis scripts will be shared through Open Science Foundation.
• IPD Sharing Time Frame: De-identified data will be shared within one year after data collection ends.
• IPD Sharing Access Criteria: Data will be available publically through Open Science Foundation upon request. We will also comply with Wellcome Trust guidance for data sharing.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Study Data/Documents

1. Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No