Bipolar disorder Mental and Behavioural Disorders Bipolar affective disorder
Conditions
Interventions
All participants will be trialled on a low-carbohydrate, high-fat ketogenic diet for a period of 8 weeks, the first two of which will be an adaptation period. Support will be via dietary supervision t
Sponsors
University of Edinburgh
NHS Lothian
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 29/04/2022: 1. Meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-4) diagnostic criteria for bipolar disorder for at least 1 year, assessed using the MINI Neuropsychiatric Interview 2. Clinically stable and currently euthymic, defined as 3 months with no major mood episodes (major depression lasting at least 2 weeks or hypomania/mania lasting at least 1 week), assessed using the MINI Neuropsychiatric Interview 3. Aged 18 to 70 years 4. Able to provide informed consent to take part in the study 5. Able to speak, read and understand English to a level whereby they can understand the participant information sheet (PIS) 6. Currently living in Scotland Previous participant inclusion criteria: 1. Meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-4) diagnostic criteria for bipolar disorder for at least 1 year, assessed using the MINI Neuropsychiatric Interview 2. Clinically stable and currently euthymic, defined as 3 months with no major mood episodes (major depression lasting at least 2 weeks or hypomania/mania lasting at least 1 week), assessed using the MINI Neuropsychiatric Interview 3. Aged 18 to 70 years 4. Able to provide informed consent to take part in the study 5. Able to speak, read and understand English to a level whereby they can understand the participant information sheet (PIS)
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 29/04/2022: 1. Pregnancy or breastfeeding (or those planning to become pregnant within 3 months) 2. Active substance misuse with alcohol or illicit drugs 3. Use of the ketogenic diet in the previous 2 months 4. Currently following a vegan diet 5. Admission to hospital within the past 3 months 6. Current involvement in another research study 7. Inability to complete baseline assessments 8. Liver or kidney disease 9. Cardiovascular disease 10. Severe hyperlipidaemia 11. Type 1 diabetes 12. Insulin dependent type 2 diabetes 13. Currently training for or undertaking very high energy requirement activities (as judged by the study dietitian) Previous participant exclusion criteria: 1. Pregnancy or breastfeeding (or those planning to become pregnant within 3 months) 2. Active substance misuse with alcohol or illicit drugs 3. Use of the ketogenic diet in the previous 2 months 4. Currently following a vegan diet 5. Admission to hospital within the past 3 months 6. Current involvement in another research study 7. Inability to complete baseline assessments 8. Liver or kidney disease 9. Cardiovascular disease 10. Severe hyperlipidaemia 11. Type 1 diabetes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The feasibility and acceptability of the ketogenic diet as an intervention for bipolar disorder for a future trial. Data will be collected on a range of parameters to understand how to make all aspects of the study workable for a subsequent trial: 1. Timeline estimates for future trial recruitment by measuring the number of interested participants and fully recruited participants from each avenue of recruitment during the estimated 4-month recruitment period 2. Participant level of compliance with dietary interventions measured using fidelity checklists at weeks 0, 2, 4, 6, and 8, and daily ketone measurements during the 8-week intervention period 3. Participant level of compliance with study assessments as recorded on the case report form at baseline and week 8 4. Participant level of compliance with continuous study assessments measured using data from the study devices and apps (actigraph device, ketomojo device and app, and ilumivu app) during the 10-week study period 5. Quality of life measured using the EQ5D-5L at baseline and week 8 6. Productivity and activity impairment measured using the Work Productivity and Activity Impairment Questionnaire at baseline and week 8 7. Participant resource use measured using a Within Trial Resource Use Questionnaire at baseline and week 8 8. Staff time and cost in delivering dietary interventions, measured by keeping contemporaneous records throughout the 10-week study period 9. Attrition rate measured using the number of participants who consent to participate who remain in the study until the end of follow-up at 10 weeks, to help inform estimation of sample size for a future trial 10. Acceptability and experience of the study participants evaluated via telephone interviews after the main study has ended as part of a process evaluation | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Mood stability measured by the Affective Lability Scale (ALS18) and Beck Depression Inventory (BDI) at baseline and at 8-week follow-up 2. Hypomania/mania symptoms measured using the Young Mania Rating Scale (YMRS) at baseline and 8-week follow up 3. Glucose/ketone ratio measured using ketomojo devices daily throughout the 10 week study period 4. Identification of specific metabolic changes in glucose, ketones and tricarboxylic acid (TCA) metabolites associated with the KD that are predicted by the study hypothesis, measured using serum and brain MRI measures at baseline and week 8 5. Mood, energy, speed of thought, impulsivity and anxiety measured using visual analogue scales from 1-100 at daily ecological momentary assessments during the 10-week study period 6. Episodes of bipolar depression and hypomania/mania occurring during the study period assessed by the MINI Neuropsychiatric assessment at baseline and week 8 7. Sleep duration and circadian activity/rest rhythmicity parameters assessed by actigraphs throughout the 10-week period (to include 2 weeks of stepping down the diet) | — |
Countries
Scotland, United Kingdom
Outcome results
None listed