Comparison of a ketogenic diet and NHS healthy eating guidance for bipolar depression: a randomised controlled trial

Evaluating nutritional ketosis versus NHS Eatwell guide for bipolar depression: single blind randomised controlled trial

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN14945909

Enrollment

206

Registered

2026-08-03

Start date

2026-10-01

Completion date

Unknown

Last updated

2026-08-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bipolar depression Mental and Behavioural Disorders

Interventions

ENERGISE-BD is a single blind randomised controlled trial of nutritional ketosis versus the NHS EatWell guide for the treatment of bipolar depression. Participants will be randomised in a 1:1 ratio

Eligibility

Sex/Gender

All

Age

18 Years to 100 Years

Inclusion criteria

Inclusion criteria: 1. Adults (aged 18 and over) with a primary* diagnosis of bipolar disorder (BD-I or BD-II), confirmed by the Structured Clinical Interview for DSM5 (Diagnostic and Statistical Manual of Mental Disorders, fifth edition), (SCID5) 2. Bipolar depression symptoms of at least moderate clinical severity on the PHQ-9 (defined as a score of 10 or above) *Other comorbid psychiatric diagnoses are permitted (apart from eating disorders and substance misuse/dependence)

Exclusion criteria

Exclusion criteria: 1. Currently in need of acute inpatient, crisis resolution, or home treatment services 2. Does not have capacity to consent 3. Previous use of nutritional ketosis within 2 months 4. Current use of weight loss medications (such as semaglutide or tirzepatide) 5. Inability to complete mandatory study assessments 6. No access to a smartphone and/or unwilling to add the KetoMojo app to their smartphone 7. Specific contraindications for the nutritional ketosis intervention: 7.1. Pregnancy, breastfeeding, or planning to become pregnant within 3 months 7.2. Liver failure 7.3. Pancreatitis (acute and past history) 7.4. Chronic kidney disease 7.5. Type I diabetes 7.6. Use of SGLT-2 inhibitors 7.7. Recent stroke or myocardial infarction 7.8. Heart failure 7.9. Cardiac arrhythmias 7.10. Respiratory failure 7.11. Active infections 7.12. Cancer 7.13. Hyperuricaemia 7.14. Severe hyperlipidaemia (familial hypercholesterolaemia, severe hypertriglyceridaemia, or total cholesterol >7.5 mmol/L) 7.15. Participant-reported inborn error of metabolism affecting fatty acid transport/oxidation, including organic acidurias and mitochondrial fatty acid beta-oxidation disorders 8. Past history of an eating disorder (bulimia or anorexia) 9. Currently only eating a vegan or exclusively plant-based diet 10. Other major primary psychiatric disorder that is not bipolar disorder, or major neurological disorders 11. Harmful current use of or dependence on psychoactive substances (including alcohol) 12. Currently enrolled in an interventional research study

Design outcomes

Primary

Measure	Time frame
Depressive symptoms measured using Patient Health Questionnaire (PHQ-9) score of 6 or more at baseline and 12 week post randomisation	—

Secondary

Measure	Time frame
1. Severity of depression symptoms measured using the Patient Health Questionnaire-9 (PHQ-9) at baseline, 12 weeks and 24 weeks post randomisation 2. Anxiety symptoms measured using the Generalised Anxiety Disorder Questionnaire (GAD-7) at baseline, 12 weeks and 24 weeks post randomisation 3. Mania symptoms measured using the Altman Self-Rating Mania Scale (ASRM) at baseline, 12 weeks and 24 weeks post randomisation 4. Health-related quality of life measured using the EuroQol EQ-5D-5L at baseline, 12 weeks and 24 weeks post randomisation 5. Functional impairment measured using the Functioning Assessment Short Test (FAST) at baseline, 12 weeks and 24 weeks post randomisation 6. Concurrent medication use (psychiatric and other medications) measured using study-recorded medication data at baseline, 12 weeks and 24 weeks post randomisation 7. Continuation of allocated diet intervention measured using study-recorded intervention adherence data at baseline, 12 weeks and 24 weeks post randomisation 8. Feasibility of collecting health economic resource use consequences and associated costs of a nutritional ketosis intervention compared to the NHS EatWell Guide for bipolar depression measured using a bespoke health economic resource use questionnaire at 12 weeks and 24 weeks post randomisation 9. Body mass index (BMI) measured using BMI calculated from measured height and weight at baseline and 12 weeks post randomisation 10. Weight change from baseline (percentage) measured using percentage change in body weight calculated from measured weight at baseline and 12 weeks post randomisation 11. Blood pressure (BP) measured using blood pressure measurement at baseline and 12 weeks post randomisation 12. Glycated haemoglobin (HbA1c) measured using an HbA1c blood test at baseline and 12 weeks post randomisation 13. Insulin resistance (C-peptide and glucose) measured using blood tests for C-peptide and glucose at baseline and 12 weeks post randomisation 14. Lipid profile (total cho	—

Measure

Time frame

1. Severity of depression symptoms measured using the Patient Health Questionnaire-9 (PHQ-9) at baseline, 12 weeks and 24 weeks post randomisation 2. Anxiety symptoms measured using the Generalised Anxiety Disorder Questionnaire (GAD-7) at baseline, 12 weeks and 24 weeks post randomisation 3. Mania symptoms measured using the Altman Self-Rating Mania Scale (ASRM) at baseline, 12 weeks and 24 weeks post randomisation 4. Health-related quality of life measured using the EuroQol EQ-5D-5L at baseline, 12 weeks and 24 weeks post randomisation 5. Functional impairment measured using the Functioning Assessment Short Test (FAST) at baseline, 12 weeks and 24 weeks post randomisation 6. Concurrent medication use (psychiatric and other medications) measured using study-recorded medication data at baseline, 12 weeks and 24 weeks post randomisation 7. Continuation of allocated diet intervention measured using study-recorded intervention adherence data at baseline, 12 weeks and 24 weeks post randomisation 8. Feasibility of collecting health economic resource use consequences and associated costs of a nutritional ketosis intervention compared to the NHS EatWell Guide for bipolar depression measured using a bespoke health economic resource use questionnaire at 12 weeks and 24 weeks post randomisation 9. Body mass index (BMI) measured using BMI calculated from measured height and weight at baseline and 12 weeks post randomisation 10. Weight change from baseline (percentage) measured using percentage change in body weight calculated from measured weight at baseline and 12 weeks post randomisation 11. Blood pressure (BP) measured using blood pressure measurement at baseline and 12 weeks post randomisation 12. Glycated haemoglobin (HbA1c) measured using an HbA1c blood test at baseline and 12 weeks post randomisation 13. Insulin resistance (C-peptide and glucose) measured using blood tests for C-peptide and glucose at baseline and 12 weeks post randomisation 14. Lipid profile (total cho

—

Countries

England, Scotland, United Kingdom

Contacts

Public ContactLorna Dewar

energise-bd.trial@ed.ac.uk-

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Aug 25, 2026