NCT06091163Completed
Ketogenic Diet for Treatment-Resistant Depression: Dietary Interventions for MEntal Health Study (DIME)
A Randomised Controlled Trial Evaluating the Efficacy and Mechanisms of a Ketogenic Diet as an Adjunctive Treatment for People With Treatment-resistant Depression
Source: ClinicalTrials.gov · Last updated 12 Feb 2025
Brief summary (registry, in English)
Depression is a debilitating chronic illness affecting 1 in 6 adults in the United Kingdom (UK) at any one time. Antidepressants and psychological therapy are the main treatments, but some people do not respond to these. Neurons and signals in the brain are greatly disrupted in people with severe depression. A ketogenic diet, a high-fat and very low-carbohydrate diet, supplies a form of energy that appears to help brain cells communicate and may improve the treatment of depression. Our goal is to find out whether a ketogenic diet could be an additional effective treatment for patients with depression for which antidepressants do not work. Using social media advertising, 100 patients, ages 18-65, who have previously tried at least two different antidepressant medications within the current depressive episode will be recruited. Enrolment, consent, and data collection will be collected online using self-report questionnaires. Participants will be allocated by minimisation 1:1 to the KD group or control group based on depressive severity (moderately severe vs. severe) and body mass index (\<30kg/m2 vs. 30+ kg/m2). The intervention group will receive 6-weeks of prepared ketogenic diet meals (3 meals with snacks per day) and weekly ketogenic diet-focused nutrition counselling. The control group will be asked to follow a diet to reduce their saturated fat intake and increase vegetable consumption by one portion a day. The control group will receive vouchers to assist with purchases and will be provided with weekly nutritional counselling. Existing treatment for depression will remain in both groups. The primary outcome is the change in depression symptoms at six weeks. All participants will complete assessments of depression and anxiety every two weeks, starting before treatment to post-intervention (week 6), and again at week 12. Additional outcomes include participants' ability to experience pleasure, quality of life, ability to socialise and work, cognitive processing, morning cortisol, and gut microbiome. At all stages of the study, adults with lived experience of depression will advise the research team to take into account the needs and views of patients. This study will provide evidence of whether following a ketogenic diet leads to a short-term improvement in depression in people whose depression cannot be relieved by antidepressants.
- Status (registry)
- Completed
- Study type
- Interventional
- Enrollment
- 88 (actual)
- First submitted
- 13 Oct 2023
- Start date
- 22 Feb 2024
- Primary completion date
- 15 Jun 2024
- Lead sponsor
- University of Oxford
- Diseases
- Depression
- NCT number
- NCT06091163
What you commit to
- Study type: Interventional
- Participants enrolled: 88
- From 22 Feb 2024 to the primary completion date, 15 Jun 2024
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Currently receiving, or have received, in-patient psychiatric treatment or electroconvulsive therapy (electric shock to the brain under brief general anaesthetic) within the past year, or scheduled to receive such treatment during the study
- Currently using St John's wort or other remedies for depression that were bought without a doctor's prescription
- Have unstable or severe medical conditions (e.g., cancer, cardiovascular, renal, lung, psychiatric, or bleeding disorders, diabetes, etc.), currently receiving cancer treatment except hormonal treatment for breast cancer or non-melanoma skin cancer treatment
- Have scheduled a major surgery in the next 3 months
Other illness
- Ever had an eating disorder, bipolar disorder, schizophrenia, or psychosis
- Have epilepsy
- Have serious food allergies (experiencing food hypersensitivity that leads to anaphylaxis or other severe symptoms, which may require hospitalisation or are life-threatening) or otherwise require a special diet that cannot be accommodated within a KD such as phenylketonuria or lactose intolerance
- Have gallstones, renal tubular acidosis, kidney stones, small bowel malabsorption or a history of pancreatitis
Lab values
- Treated with insulin, sulfonylureas, Glucagon-like peptide-1 (GLP-1) agonists, or Sodium-glucose co-transporter-2 (SGLT2) inhibitors
Other
- Currently following a low carbohydrate or ketogenic diet
- Currently following a vegan or vegetarian diet as these diets are more challenging to accommodate in a Ketogenic Diet and adding vegetables in the control group is unlikely to be seen as helpful.
- Currently have suicidal ideation with intent\* or attempted suicide within the past two months
- Have substance use or alcohol dependence
- Women who are pregnant, planning pregnancy in the next three months, or breastfeeding
- Have a body mass index (BMI) of \<18.5 kg/m2
- Taking part in other studies that may compromise this study or this study may compromise the other study/ies
- Have read the trial protocol or the clinical trial registration information and therefore are unblinded
- Live in the same household as another participant in the trial
- Not able to complete the online task with a tablet/computer
- Not willing to provide saliva, urine and stool samples
Who the study is looking for
- Aged 18-65 years
- Have been diagnosed with depression
- Currently on an antidepressant medication for a period of 4-weeks or longer
- Have tried 2 or more antidepressant treatment trials of adequate dose and duration within the current depressive episode to which they did not fully respond. An adequate treatment trial is defined as at least 4 weeks of a medication at a minimum National Institute for Health and Care Excellence (NICE) approved dose
- With a Patient Health Questionnaire-9 (PHQ-9) total score greater than or equal to 15 at baseline
- Able to understand and be willing to adhere to the demands of the study
- Provision of written informed consent
- Have access to a tablet/computer for online assessments, follow-ups with the registered dietitian, and able to attend appointments for assessments and treatment and adhere to study procedures
- Have both a fridge and a freezer at home
- Complete all baseline assessments
Age in the registry: 18 years to 65 years · Sex: All · Does not accept healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| University of Oxford Coordinator of this site? Confirm its status | Oxford | United Kingdom | Unknown status |
Related publications
- A Ketogenic Diet for Treatment-Resistant Depression: A Randomized Clinical Trial.JAMA Psychiatry · 2026 · PMID 41637092
This page is information, not medical advice. Discuss any trial with your doctor.