Clinical trial NCT06560957: SYNCED - SYNChronized Eating in Bipolar Depression Study
Official title: Feasibility and Acceptability of Adjunctive Time Restricted Eating in Bipolar Disorder: a Pilot Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Bipolar Depression
Bipolar I Disorder
Bipolar II Disorder
Lead sponsor: University of Ottawa
Sponsor class: OTHER
Collaborators: name: Ottawa Hospital Research Institute
First posted: 2024-08-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Bipolar disorders (BD) are a group of complex disorders that impact mood, behaviour and cognition and are known to cause significant suffering and impairment. Circadian rhythm (your internal day/night "clock") disruption, which can involve changes in sleep-wake cycles, frequently occurs in BD. Both depression and mania are accompanied by circadian disruption. These disruptions are hypothesized to lead to mood worsening, metabolic dysfunction and inflammation. If circadian dysfunction plays a significant role in the symptoms and trajectory of BD, then treatment approaches that target these functions may lead to better outcomes. One such approach is dietary interventions. Time restricted eating (TRE) is a dietary tool that restricts the eating to an 8-12 hour window, without changing diet quality or caloric intake. Studies involving time restricted eating have been done in other conditions with promising results. There have been no studies done for mood disorders in general or bipolar disorder specifically. In this proposal, the investigators will assess two dietary interventions (TRE and nutritional counselling) to examine how TRE may represent a safe and viable adjunct to traditional treatments. The investigators aim to compare TRE with nutritional counselling, while all participants continue to receive usual care. Participants will receive support from a registered dietician and will be instructed on dietary habits. Half of participants will receive nutritional counselling and half will be asked to do TRE. Those in the TRE group will be asked to select a 10-hour window to consume all food and non-water beverages for the 8-week period. Participants will be asked to complete a screening visit to determine eligibility, and then will complete questionnaires at baseline, week 4 and week 8 examining symptoms of their illness and cognition. Participants will also provide a blood sample at baseline and week 8 for standard biochemistry tests, pregnancy testing (if applicable), and to examine inflammatory markers. Participants will also wear an actigraphy watch which provides wireless continuous monitoring of movements and ambient light. The primary outcome is feasibility and acceptability (do people agree to participate, complete the study, and follow the intervention; what do they think of the intervention). Secondary outcomes include changes in depression, anxiety, sleep, and cognition. Exploratory outcomes include inflammatory markers and circadian disruption.

Detailed description: Given the lack of studies evaluating time restricted eating (TRE), this pilot study aims to examine the feasibility and acceptability of TRE as a prelude to a future multi-centre randomized controlled trial (RCT) evaluating efficacy. If adjunctive TRE is found to be feasible, this will pave the way for a novel and safe intervention which may have the potential to treat circadian dysfunction, metabolic side effects and improve mood and cognitive outcomes in patients with BD.

To evaluate the feasibility and acceptability of adjunctive 10-hour TRE with treatment as usual relative to nutritional counselling and treatment as usual for the treatment of depression associated with bipolar disorder. To do this, the investigators will estimate the rate (proportion) of eligible people who are willing to participate, participants who drop out of the trial and participants who adhere to their allocated intervention.

First, the investigators hypothesize that the investigators would achieve our recruitment target of 40 patients with BD within the study's 18-month duration and retain at least 70% of participants through the follow-up period to evaluate feasibility. The investigators will also be able to estimate what level of adherence could be expected following a single intervention with a 4-week reminder. Second, the investigators hypothesize that participants would complete the intervention and find it acceptable.

Secondary Objectives To assess if TRE leads to meaningful reductions in markers of depression, anxiety, sleep, quality of life, and cognition.

The investigators hypothesize a greater reduction in depressive symptoms, anxiety symptoms compared to that seen in the control group. The investigators also hypothesize improvements in sleep, quality of life and cognition compared to the control group.

Exploratory Objectives Effects on inflammatory markers and circadian disruption will be additionally explored.

Eligibility criteria: Inclusion Criteria:

1. Be 18-55 years old
2. Have a diagnosis of bipolar I or bipolar II disorder, confirmed by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) Research Version (SCID-RV)
3. Have mild to moderate depression symptoms as indicated by a score of ≥12 and ≤30 on MADRS and ≤12 on Young Mania Rating Scale (YMRS).
4. Be willing to use email for study activities
5. Females of childbearing potential are willing to follow highly effective methods of contraception (mentioned below) for the duration of study\*
6. Be able and willing to use email and a smartphone application for the duration of the trial
7. Participants must be able to speak, read, write and understand English or French.
8. Be willing and able to provide informed consent.

Exclusion Criteria:

1. Have clinically significant suicidal ideation, defined as ≥ 4 on MADRS suicide item
2. Have any catatonic symptoms, eating disorders, borderline personality disorder and substance use disorders as measured by the Structured Clinical Interview for the DSM-5 Research Version (SCID-RV)
3. Have any unstable or inadequately treated neurological and medical conditions
4. Have had prior bariatric surgery
5. Be taking hypoglycemia inducing medications
6. Be pregnant or lactating
7. Currently on stimulant medications
8. Be participating in any other diet or weight management program for the duration of the trial.
9. Have any contraindication to fasting as judged by the assessing clinician.
10. Recently started taking a Canadian Network for Mood and Anxiety Treatments (CANMAT) recommended treatment18 for the management of acute bipolar depressive episode, but has not had a trial for a minimum of 6 weeks with adequate doses.
11. Recently (i.e. within the past 8 weeks) began structured psychotherapy (i.e. cognitive-behavioral therapy, interpersonal psychotherapy, family-focused therapy, or interpersonal and social rhythm therapy).
12. Have any other medical condition for which physician or investigator team expresses concern about safety or ability to participate in the study.

Primary outcomes:
measure: Number of participants who complete the study
timeFrame: 18 months
measure: Time to recruit all participants
timeFrame: 18 months
measure: Intervention adherence
timeFrame: 18 months
measure: Rate of participation
timeFrame: 18 months
Secondary outcomes:
measure: Depression severity - Montgomery-Åsberg Depression Rating Scale
timeFrame: Screening, Baseline (week 1), Week 4, Week 8
measure: Cognitive dysfunction - Cognitive Complaints in Bipolar Disorder Rating Assessment
timeFrame: Baseline (week 1), Week 4, Week 8
measure: Cognitive Dysfunction - Screen for Cognitive Impairment in Psychiatry
timeFrame: Baseline (week 1), Week 4, Week 8
measure: Anxiety severity - Hamilton Anxiety Rating Scale
timeFrame: Baseline (week 1), Week 4, Week 8
measure: Anxiety severity - Generalized Anxiety Disorder-7
timeFrame: Baseline (week 1), Week 4, Week 8
measure: Biological Rhythms - Biological Rhythm Interview for Assessment in Neuropsychiatry
timeFrame: Baseline (week 1), Week 4, Week 8
measure: Sleep Quality - Reduced Pittsburgh Sleep Quality Index
timeFrame: Baseline (week 1), Week 4, Week 8
measure: 19-Item Self-Assessment Questionnaire for Sleep Rhythms, Habits and Fatigue (MEQ)
timeFrame: Baseline (week 1), Week 4, Week 8
measure: Function - Global Assessment of Functioning
timeFrame: Baseline (week 1), Week 4, Week 8
measure: Symptom Severity and Improvement - Clinical Global Impressions-BP-Severity & Improvement (CGI-BP I&S)
timeFrame: Baseline (week 1), Week 4, Week 8
measure: Psychological Dysfunction - Functioning assessment short test (FAST)
timeFrame: Baseline (week 1), Week 4, Week 8
measure: Quality of Life - Brief Quality of Life in Bipolar Disorder Questionnaire
timeFrame: Baseline (week 1), Week 4, Week 8
measure: Mania severity - Young Mania Rating Scale
timeFrame: Screening, Baseline (week 1), Week 4, Week 8
Other outcomes:
measure: Change in circadian rhythms
timeFrame: Week 0, Week 9
measure: Change in C-reactive protein levels
timeFrame: Baseline (week 1), Week 8
measure: Change in cytokine levels
timeFrame: Baseline (week 1), Week 8
measure: Change in red blood cell count
timeFrame: Baseline (week 1), Week 8
measure: Change in hemoglobin
timeFrame: Baseline (week 1), Week 8
measure: Change in hematocrit
timeFrame: Baseline (week 1), Week 8
measure: Change in lymphocyte count
timeFrame: Baseline (week 1), Week 8
measure: Change in blood chemistry
timeFrame: Baseline (week 1), Week 8
measure: Change in liver functions
timeFrame: Baseline (week 1), Week 8
measure: Change in total bilirubin
timeFrame: Baseline (week 1), Week 8
measure: Change in serum creatinine
timeFrame: Baseline (week 1), Week 8
Locations:
Study officials:
affiliation: The Ottawa Hospital
name: Gayatri Saraf, MD
role: PRINCIPAL_INVESTIGATOR
References: