Comparing Ketogenic Diet with Canadian Food Guide-Aligned Diet for major depressive disorder (MDD)
Official title: Ketogenic Diet and Neuromodulation in Treatment Resistant Depression
Adjunctive Low-carb Ketogenic Diet to Enhance Imaging-guided Neuromodulation in Treatment Resistant Depression
- 2 groups
- One site, in Toronto
- Recruiting
Interventions
- Medical device
Accelerated Intermittent Theta Burst Stimulation (iTBS)
Intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS), is a non-invasive brain stimulation technique approved by the FDA and Health Canada for the treatment of TRD. In this study, participants will receive an accelerated course of imaging-guided, neuronavigated left dorsolateral prefrontal cortex (DLPFC) iTBS targeted based on functional connectivity with the subgenual anterior cingulate cortex (sgACC). Stimulation protocol consists of 1800 pulses per session, delivered at 110% of resting motor threshold, with 50-minute inter-session intervals, for 8 sessions per day over 5 consecutive days.
- Behavioural therapy
Ketogenic Diet
A well-formulated ketogenic diet consisting of low carbohydrate, moderate protein, and high fat intake, designed to achieve and maintain nutritional ketosis (blood ketone levels of 0.5 to 3 mmol/L). Delivered with dietitian-led counseling and monitored via finger-stick ketone and glucose testing.
- Behavioural therapy
Canadian Food Guide-Aligned Diet
A Canadian Food Guide-aligned diet emphasizing balanced intake of vegetables, fruits, whole grains, and protein foods, without specific macronutrient restrictions. Delivered with dietitian counseling matched in frequency and duration to the ketogenic diet arm, and monitored via dietary logs, metabolic assessments, and finger-stick glucose testing.
Canadian Sites (1)
1 of 1 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario
Eligibility Criteria
See who this study is looking for29 criteria
The trial’s own eligibility text, word for word from the registry. Only the trial site can say who takes part.
Inclusion
- +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 (PHQ ≥ 10)
- +Meeting criteria for treatment-resistant depression (TRD), defined as either: (1) failure to achieve a clinical response to ≥2 adequate antidepressant treatment trials for unipolar depression, OR (2) inability to tolerate ≥2 separate antidepressant treatment trials for unipolar depression, as assessed using the Antidepressant Treatment History Form (ATHF), with a score of ≥3 in the current episode
- +No rTMS treatment received in the current depressive episode (prior rTMS in a previous episode is permitted); no failure to respond to a course of electroconvulsive therapy (ECT) in the current depressive episode
- +Able to provide informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more →
- +Available for the 12-week intervention and willing to follow either a ketogenic or Canadian Food Guide-aligned diet
- +No increase or initiation of any antidepressant or antipsychotic medication in the 4 weeks prior to screeningScreeningThe checks done before joining, to see whether a study fits.Read more →
Exclusion
- −GI disorders or food allergies incompatible with dietary protocols
- −Concomitant major unstable medical illness as determined by a study physician
- −Lifetime diagnosis of bipolar I or bipolar II disorder, or a primary psychotic disorder, as confirmed by a structured psychiatric interview
- −Current psychotic symptoms
- −Diagnosis of obsessive-compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalised anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → to be primary and causing greater impairment than MDD
- −Diagnosis of any personality disorder assessed by a study investigator to be primary and/or causing greater impairment than MDD
- −History of epilepsy, stroke, or major neurological conditions, or a history of a primary seizure disorder or a seizure associated with an intracranial lesion
- −Physical or cognitive disability interfering with participation
- −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 Ketogenic diet
- −Habitual low-carb diet in the past 6 months
- −Alcohol use \>3 drinks/day or \>14/week
- −Use of anticonvulsants (benzodiazepines with a dose of \<2 lorazepam equivalents will be permitted), GABA agonists, or medications reducing TMS efficacy
- −Contraindications to MRI
- −Unwillingness to perform daily finger-stick testing
- −Inability to access or prepare KD-compliant foods if assigned
- −Unable to provide informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → on their own
- −Pregnancy, nursing, or intent to become pregnant during study
In plain language
Assembled directly from this trial’s registry record. Every sentence traces to a field below — nothing here is generated or interpreted.
What this study is
This study is testing a treatment for a condition.
This study is not organised into the usual phase numbers — that is common for device, behavioural, and diagnostic research.
From the trial registry
Built from these fields:
- designModule.designInfo.primaryPurpose
- designModule.phases
Who receives what
There are 2 groups in this study.
Group A receives Ketogenic Diet, together with one or more of: Accelerated Intermittent Theta Burst Stimulation (iTBS).
Registry label: A: Ketogenic Diet
Group B, the comparison group, receives Canadian Food Guide-Aligned Diet, together with one or more of: Accelerated Intermittent Theta Burst Stimulation (iTBS).
Registry label: B: Canadian Food Guide-Aligned Diet
From the trial registry
Built from these fields:
- armsInterventionsModule.armGroups[].label
- armsInterventionsModule.armGroups[].type
- armsInterventionsModule.armGroups[].interventionNames
How the study is run
Which group you would be placed in is decided by chance, like a coin flip — not by you and not by your doctor.
One group of people involved — usually the participants — is not told which treatment is which.
From the trial registry
Built from these fields:
- designModule.designInfo.allocation
- designModule.designInfo.maskingInfo.masking
Is there a placebo?
This study does not list a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group.
One group receives an existing treatment, so the two can be compared.
From the trial registry
Built from these fields:
- armsInterventionsModule.armGroups[].type
- armsInterventionsModule.armGroups[].interventionNames
Who the study is looking for
The study lists an age range of 18 years to 65 years.
The study is open to people of any sex.
The study does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
These are the criteria the study lists. Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part.
From the trial registry
Built from these fields:
- eligibilityModule.minimumAge
- eligibilityModule.maximumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How big and how long
The study aims to enrol about 60 people.
The study is currently expected to finish around January 2028.
The main measurement is taken over: BaselineBaselineYour starting measurements, taken before treatment begins.Read more →, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS).
From the trial registry
Built from these fields:
- designModule.enrollmentInfo.count
- statusModule.completionDateStruct.date
- outcomesModule.primaryOutcomes[].timeFrame
What the study measures
Change in Depression Score on the Montgomery-Asberg Depression Rating Scale (MADRS) — measured over BaselineBaselineYour starting measurements, taken before treatment begins.Read more →, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS).
Changes in Ketone Levels — measured over Baseline through week 12.
Incidence of Treatment-Emergent Adverse EventsAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → [Safety and Tolerability] — measured over Baseline through week 12.
From the trial registry
Built from these fields:
- outcomesModule.primaryOutcomes[].measure
- outcomesModule.primaryOutcomes[].timeFrame
Source: NCT07376018 on ClinicalTrials.gov. The full registry text is further down this page — this summary never replaces it.
Not medical advice. What do these terms mean?
What is being tested — in plain terms
About Accelerated Intermittent Theta Burst Stimulation (iTBS)Device
Intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS), is a non-invasive brain stimulation technique approved by the FDA and Health Canada for the treatment of TRD. In this study, participants will receive an accelerated course of imaging-guided, neuronavigated left dorsolateral prefrontal cortex (DLPFC) iTBS targeted based on functional connectivity with the subgenual anterior cingulate cortex (sgACC). Stimulation protocol consists of 1800 pulses per session, delivered at 110% of resting motor threshold, with 50-minute inter-session intervals, for 8 sessions per day over 5 consecutive days.
From the trial registry — its own words, unedited.
What a device is here: A physical instrument, implant, app or piece of equipment being studied.
Read the full explanation → · in clinical review
About Ketogenic DietBehavioural
A well-formulated ketogenic diet consisting of low carbohydrate, moderate protein, and high fat intake, designed to achieve and maintain nutritional ketosis (blood ketone levels of 0.5 to 3 mmol/L). Delivered with dietitian-led counseling and monitored via finger-stick ketone and glucose testing.
From the trial registry — its own words, unedited.
What a behavioural is here: A programme, therapy, education, or lifestyle approach being studied.
Read the full explanation → · in clinical review
About Canadian Food Guide-Aligned DietBehavioural
A Canadian Food Guide-aligned diet emphasizing balanced intake of vegetables, fruits, whole grains, and protein foods, without specific macronutrient restrictions. Delivered with dietitian counseling matched in frequency and duration to the ketogenic diet arm, and monitored via dietary logs, metabolic assessments, and finger-stick glucose testing.
From the trial registry — its own words, unedited.
What a behavioural is here: A programme, therapy, education, or lifestyle approach being studied.
Read the full explanation → · in clinical review
Common questions
Answered from this trial’s registry record. Where the record doesn’t say, these answers say so rather than filling the gap.
Am I eligible for this trial?
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part. Concord cannot make that determination, and neither can any tool that has not examined you.
What the study lists: an age range of 18 years to 65 years.
The full inclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more → and exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → are published on this page, exactly as the study team wrote them.
The useful next step is to bring this trial to your doctor. Answering a few questions first gives them something concrete to review.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.maximumAge
- eligibilityModule.eligibilityCriteria
Is there a placebo?
This study does not list a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group.
One group receives an existing treatment so the two can be compared.
From the trial registry
- armsInterventionsModule.armGroups[].type
Would I know which treatment I am getting?
One group of people involved — usually the participants — is not told which treatment is which.
Which group you would be placed in is decided by chance, like a coin flip — not by you and not by your doctor.
From the trial registry
- designModule.designInfo.maskingInfo.masking
- designModule.designInfo.allocation
Who can join?
The study lists an age range of 18 years to 65 years.
It is open to people of any sex.
It does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can confirm whether a particular person can take part.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.maximumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How long would this take?
The study's main measurement is taken over: BaselineBaselineYour starting measurements, taken before treatment begins.Read more →, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS).
The study as a whole is currently expected to finish around 2028-01.
How long any one person takes part can differ from the study length. The study team can tell you what the schedule looks like in practice.
From the trial registry
- outcomesModule.primaryOutcomes[].timeFrame
- statusModule.completionDateStruct.date
How many people are taking part?
The study aims to enrol about 60 people.
From the trial registry
- designModule.enrollmentInfo.count
Where is this happening?
This study lists one location: Toronto, Ontario, Canada.
Sites can open and close during a study, so confirm with the team before travelling.
From the trial registry
- trial_locations
About This Trial
The goal of this clinical trial is to learn if combining a ketogenic diet with a personalized, accelerated brain stimulation treatment (iTBS) works better than iTBS with a standard healthy diet to reduce depression symptoms in adults with treatment-resistant depression. The main questions it aims to answer are: * Does iTBS combined with a ketogenic diet improve depression symptoms more than iTBS combined with a standard healthy diet? * Does the ketogenic diet change ketone levels over time? * Is it safe, tolerable, and feasible to follow a ketogenic diet during accelerated iTBS treatment? We will compare a ketogenic diet to a Canadian Food Guide-aligned diet, both combined with iTBS, measuring depression severity using standard clinician-rated and self-report scales. Participants will: * Follow either a ketogenic diet or a standard healthy diet for 12 weeks, starting with a 3-week lead-in period before iTBS begins * Undergo a course of personalized, imaging-guided accelerated iTBS while continuing their assigned diet * Complete clinical and cognitive assessments, blood tests, and brain MRI scans before and after treatment * Have their ketone levels checked regularly throughout the 12-week period
Worth passing on?
Save it to the Care Package and send it to them, or to their doctor, in one message. Whether they follow it up is theirs to decide.
Review the Care PackageThis page is for informational purposes only and does not constitute medical advice. Clinical trial eligibility can only be determined by the trial site after proper screening. Trial information is sourced from ClinicalTrials.gov and may not reflect the most current status. Always consult your healthcare provider before making decisions about clinical trial participation.