Ketogenic Diet Therapy Major Depressive Disorder

NCT05558995 | Unknown

• 1 other identifier: KETOOPEN
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This research program will examine the feasibility as assessed through rates of adherence, tolerability, and safety of the ketogenic diet for individuals with Major Depressive Disorder (MDD) who are not achieving symptomatic remission with first line antidepressants such as the Serotonin Selective Inhibitors (SSRIs). Driven by robust data on the benefits of ketogenic diet in epilepsy and by preliminary data in animal models demonstrating its effects on depressive behaviors, there is a hypothesis that ketogenic diet could be useful to treat residual depressive symptoms. As deficits in reward and pleasure (anhedonia) are the most common residual symptoms in MDD individuals with partial response to SSRIs, the ketogenic diet could be a potential adjuvant in the treatment for depression. In addition, a preliminary assessment of neuroplasticity-related biomarkers in the plasma to determine possible biological substrates for the mechanism of action of ketogenic diet in the brain will be conducted.

Conditions

Major Depressive Disorder

Keywords

Ketogenic Diet; Major depressive disorder

Outcome Measures

Primary Outcomes (1)

• Participant Adherence

  Number of participants that completed the trial/Total number of participants enrolled

  Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.

Secondary Outcomes (44)

• Changes in the Effort-based decision making

  Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.

• Changes in the serum levels of the brain-derived neurotrophic factor

  Baseline (week 0) and week 12.

• Changes in the serum level of TNF-alpha

  Baseline (week 0) and week 12.

• Changes in the serum level of Interleukin-1(IL-1)

  Baseline (week 0) and week 12.

• Changes in the serum level of Interleukin-6 (IL-6)

  Baseline (week 0) and week 12.

Study Arms (1)

MDD patient

EXPERIMENTAL

Male and female participants (N=10) with ages between 18 and 50 have a confirmed diagnosis of major depressive episode, are experiencing a current episode (following DSM-5 criteria),

Other: ketogenic diet

Interventions

ketogenic diet OTHER

All the subjects will be instructed by a nutrition professional to have at least 3 meals per day consisting of 20 g to 30 g of carbohydrate in the form of green vegetables and salad, and 80 g to 100 g of protein in the form of meat, fish, fowl, eggs, shellfish and cheese for 12 weeks. Polyunsaturated and monounsaturated fats will also be included in the diet. Micronutrients (vitamins and minerals) will be given to each subject in the form of one capsule per day. The adherence to diet will be confirmed weekly through a food log and urinary ketones assessment using dipstick to ensure that all individuals remain in a ketotic state.

MDD patient

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnostic criteria for single episode or recurrent MDD, without psychotic features, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and confirmed by the Mini International Neuropsychiatric Interview (MINI).
• \-- Moderate or severe depressive syndrome, as defined by a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater than or equal to (\>=) 20 at baseline.
• Treatment with SSRIs for at least 6 weeks, with no changes in dosing for the past 3 weeks.
• Must be capable of providing informed consent, based on the opinion of the participating physician.
• No vitamin and mineral deficiencies, specifically: vitamin B (B1, B3, B6, B9, and B12), vitamin D, iron, zinc, electrolytes (Na, K), calcium, and magnesium.

You may not qualify if:

• Has a current or prior diagnosis of schizophrenia spectrum disorders or bipolar disorder or related disorders, or intellectual disability, according to DSM-5.
• Has current or prior diagnosis of epilepsy
• Has homicidal ideation/intent or is at imminent risk of suicide per the physician's clinical judgment and/or based on the Columbia-Suicide Severity Rating Scale (C-SSRS) corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent)
• Adoption of specific dietetic habits: vegan, gluten-free, lactose-free diets or currently doing fasting for religious purposes.
• Has evidence of alcohol or drug dependence (except for nicotine and caffeine) according to DSM-5 or within 6 months prior to enrolment
• Has participated in or is currently enrolled in any clinical trial or observational study within the current episode.
• Has a medical contra-indication for ketogenic diet (e.g. metabolic disorder, cardiac arrhythmia, pregnancy or breastfeeding).

Sponsors & Collaborators

• Queen's University: lead

Study Sites (1)

Queen's University - Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

RECRUITING

Related Publications (7)

• Malhi GS, Mann JJ. Depression. Lancet. 2018 Nov 24;392(10161):2299-2312. doi: 10.1016/S0140-6736(18)31948-2. Epub 2018 Nov 2.

  PMID: 30396512 BACKGROUND

• Shelton RC, Tomarken AJ. Can recovery from depression be achieved? Psychiatr Serv. 2001 Nov;52(11):1469-78. doi: 10.1176/appi.ps.52.11.1469.

  PMID: 11684742 BACKGROUND

• Cooper JA, Arulpragasam AR, Treadway MT. Anhedonia in depression: biological mechanisms and computational models. Curr Opin Behav Sci. 2018 Aug;22:128-135. doi: 10.1016/j.cobeha.2018.01.024.

  PMID: 29503842 BACKGROUND

• Ceolin G, Breda V, Koning E, Meyyappan AC, Gomes FA, Moreira JD, Gerchman F, Brietzke E. A Possible Antidepressive Effect of Dietary Interventions: Emergent Findings and Research Challenges. Curr Treat Options Psychiatry. 2022;9(3):151-162. doi: 10.1007/s40501-022-00259-1. Epub 2022 Apr 23.

  PMID: 35496470 BACKGROUND

• Grigolon RB, Gerchman F, Schoffel AC, Hawken ER, Gill H, Vazquez GH, Mansur RB, McIntyre RS, Brietzke E. Mental, emotional, and behavioral effects of ketogenic diet for non-epileptic neuropsychiatric conditions. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Aug 30;102:109947. doi: 10.1016/j.pnpbp.2020.109947. Epub 2020 Apr 17.

  PMID: 32305355 BACKGROUND

• Brietzke E, Mansur RB, Subramaniapillai M, Balanza-Martinez V, Vinberg M, Gonzalez-Pinto A, Rosenblat JD, Ho R, McIntyre RS. Ketogenic diet as a metabolic therapy for mood disorders: Evidence and developments. Neurosci Biobehav Rev. 2018 Nov;94:11-16. doi: 10.1016/j.neubiorev.2018.07.020. Epub 2018 Jul 31.

  PMID: 30075165 BACKGROUND

• Brietzke E, Fabe J, Bambokian A, Breda V, Chaves C, Shelp J, Terpstra A, Koning E, Groll D, Milev R, McIntyre RS, Mansur RB, Soares CN, Gomes FA. Medically supervised ketogenic diet as an adjunctive treatment for moderate to severe depression: A pilot study. J Affect Disord. 2026 Apr 15;399:121079. doi: 10.1016/j.jad.2025.121079. Epub 2025 Dec 29.

  PMID: 41475571 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Elisa Brietzke, MD,PhD

  Queen's University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elisa Brietzke, MD,Ph.D

CONTACT

+1 (613) 548- 3232; Elisa.brietzke@queensu.ca

Fabiano Gomes, MD, PhD

CONTACT

fabiano.alvesgomes@queensu.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD,PhD,Professor

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: September 29, 2022
• Study Start: January 2, 2024
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)