NCT06091163: DIME

Ketogenic Diet for Treatment-Resistant Depression: Dietary Interventions for MEntal Health Study (DIME)

Completed NA Last updated 12 February 2025

What this trial tests

NA trial testing Ketogenic Diet in Treatment Resistant Depression in 88 participants. Completed in 30 September 2024.

Timeline

22 February 2024

Primary endpoint
15 June 2024

30 September 2024

Quick facts

Lead sponsor	University of Oxford
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	88
Start date	22 February 2024
Primary completion	15 June 2024
Estimated completion	30 September 2024
Sites	1 location across United Kingdom

Drugs / interventions tested

• Ketogenic Diet — full drug profile →
• Phytonutrient Diet

Conditions studied

• Treatment Resistant Depression — all drugs for Treatment Resistant Depression →
• Depression — all drugs for Depression →
• Mental Illness — all drugs for Mental Illness →
• Mental Disorder — all drugs for Mental Disorder →

Sponsor

University of Oxford

Who can join

Adults 18 to 65, any sex, with Treatment Resistant Depression or Depression. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. The Potential Role of the Ketogenic Diet in Serious Mental Illness: Current Evidence, Safety, and Practical Advice.
   Rog J, Wingralek Z, Nowak K, Grudzień M, et al · · 2024 · cited 12× · PMID 38792361 · DOI 10.3390/jcm13102819
2. A Ketogenic Diet for Treatment-Resistant Depression: A Randomized Clinical Trial.
   Gao M, Kirk M, Knight H, Lash E, et al · · 2026 · PMID 41637092 · DOI 10.1001/jamapsychiatry.2025.4431