Ketogenic Diet and Neuromodulation in Treatment Resistant Depression (NCT07376018) | Clinical Trial Compass
Not Yet RecruitingNot Applicable
Ketogenic Diet and Neuromodulation in Treatment Resistant Depression
Canada60 participantsStarted 2026-04-01
Plain-language summary
The goal of this clinical trial is to test whether combining a ketogenic diet (KD) with personalized, accelerated intermittent theta burst stimulation (iTBS) produces greater reductions in depressive symptoms than iTBS combined with a standard healthy diet in adults with treatment-resistant depression. The trial also aims to determine whether participants can feasibly follow a ketogenic diet during an accelerated iTBS treatment course and whether the diet produces measurable changes in ketone levels.
Specifically, the study aims to determine whether the combined intervention:
1. Reduces depressive symptoms
2. Increases circulating ketone levels
3. Is feasible and tolerable during accelerated iTBS treatment
Participants will begin either a KD or a Canadian Food Guide-aligned diet (CFGD) with a 3-week dietary lead-in period, after which they will undergo a course of personalized, accelerated iTBS while continuing their assigned diet. Before and after the iTBS treatment course, participants will complete clinical assessments, provide blood samples for metabolic testing, and undergo MRI scans to assess brain connectivity. Ketone levels will be measured daily throughout the 12-week dietary intervention. Within-group and between-group differences will be compared to characterize changes in clinical outcomes, metabolism, and brain functioning.
Who can participate
Age range
18 Years – 65 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Age 18-65 of any sex, gender identity, ethnicity and socioeconomic status
* Currently experiencing a major depressive episode as defined by DSM-5-TR criteria and confirmed by a study physician
* Presenting with at least moderate symptom severity (MADRS ≥ 20)
* Meeting criteria for treatment-resistant depression (TRD), defined as non-response to at least two adequate antidepressant trials
* Neuromodulation-naïve (no past rTMS or electroconvulsive therapy)
* Able to provide informed consent
* Available for the 15-week intervention and willing to follow either a ketogenic or Canadian Food Guide-aligned diet
Exclusion Criteria:
* Medical/psychiatric co-morbidities that prevent participation in the study or where depression is not the primary psychiatric symptom of concern
* History of epilepsy, stroke, or major neurological conditions, psychosis, or substance dependence within the last 6 months
* Physical or cognitive disability interfering with participation
* Females who are pregnant (self-report or via blood work), nursing, or planning a pregnancy during the timespan of the study BMI \< 20 kg/m²
* Suicide attempts in the past 12 months
* Active suicidal intent as confirmed by study psychiatrist
* Active eating disorder in the past 12 months
* Currently following a KD
* Habitual low-carb diet in the past 6 months
* GI disorders or food allergies incompatible with dietary protocols
* Alcohol use \>3 drinks/day or \>14/week
* Use of anticonvulsants (benzo…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Change in Depression Score on the Montgomery-Asberg Depression Rating Scale (MADRS)