[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100621853":3},{"organization":4,"armGroups":7,"interventions":19,"overallOfficials":27,"centralContacts":28,"locations":37,"responsibleParty":53,"collaborators":57,"id":61,"slug":62,"hasResults":63,"nctId":64,"briefTitle":65,"officialTitle":66,"acronym":67,"eligibilityCriteria":68,"healthyVolunteers":63,"sex":69,"minAge":70,"maxAge":71,"enrollmentInfo":72,"targetDuration":27,"studyType":75,"phases":76,"briefSummary":78,"conditions":79,"keywords":82,"overallStatus":96,"whyStopped":27,"lastUpdateSubmitDate":97,"lastUpdatePostDateStruct":98,"startDateStruct":101,"completionDateStruct":103,"leadSponsor":105,"locationsCount":106},{"fullName":5,"class":6},"Sunnybrook Health Sciences Centre","OTHER",[8,14],{"label":9,"type":10,"description":11,"interventionNames":12},"Ketogenic Diet","EXPERIMENTAL","Participants in this arm will begin a well-formulated ketogenic diet (low carbohydrate, moderate protein, high fat) for a 3-week dietary lead-in period prior to neuromodulation, and will continue the diet for a total of 12 weeks. The diet is designed to achieve and maintain nutritional ketosis (blood ketone levels of 0.5 to 3 mmol\u002FL). Dietitian support will be provided through scheduled counseling and ongoing monitoring using daily finger-stick ketone and glucose testing.",[13],"Device: Accelerated Intermittent Theta Burst Stimulation (iTBS)",{"label":15,"type":16,"description":17,"interventionNames":18},"Canadian Food Guide-Aligned Diet","ACTIVE_COMPARATOR","Participants in this arm will begin a Canadian Food Guide-aligned diet for a 3-week dietary lead-in period prior to neuromodulation and will continue the diet for a total of 12 weeks. The diet will emphasize balanced intake of vegetables, fruits, whole grains, and protein foods, without specific macronutrient restrictions. Dietitian counseling will be matched in frequency and duration to the ketogenic diet arm. Nutritional monitoring will include dietary logs and metabolic assessments without targeted induction of ketosis. Participants will perform daily finger-stick glucose testing.",[13],[20],{"type":21,"name":22,"description":23,"armGroupLabels":24,"otherNames":25},"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 image-guided, neuronavigated left dorsolateral prefrontal cortex (DLPFC) iTBS targeted based on functional connectivity with the subgenual anterior cingulate cortex (sgACC). Stimulation will consist of 600 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.",[15,9],[26],"repetitive transcranial magnetic stimulation (rTMS)",null,[29,34],{"name":30,"role":31,"phone":32,"phoneExt":27,"email":33},"Sean M Nestor, M.D., PhD","CONTACT","416-347-0257","sean.nestor@utoronto.ca; sean.nestor@sunnybrook.ca",{"name":35,"role":31,"phone":27,"phoneExt":27,"email":36},"Jo Donguk, PhD","donguk.jo@sri.utoronto.ca",[38],{"facility":5,"status":27,"city":39,"state":40,"zip":41,"country":42,"countryCode":43,"cosmosGeoPoint":44,"geoPoint":49,"contacts":50},"Toronto","Ontario","M4N 3M5","Canada","CA",{"type":45,"coordinates":46},"Point",[47,48],-79.39864,43.70643,{"lat":48,"lon":47},[51],{"name":30,"role":31,"phone":32,"phoneExt":27,"email":52},"sean.nestor@utoronto.ca",{"type":54,"investigatorFullName":55,"investigatorTitle":56,"investigatorAffiliation":5,"oldNameTitle":27,"oldOrganization":27},"PRINCIPAL_INVESTIGATOR","Dr. Sean Michael Nestor","Psychiatrist",[58],{"name":59,"class":60},"Baszucki Group","UNKNOWN","100621853","ketogenic-diet-and-neuromodulation-in-treatment-resistant-depression-100621853",false,"NCT07376018","Ketogenic Diet and Neuromodulation in Treatment Resistant Depression","Adjunctive Low-carb Ketogenic Diet to Enhance Imaging-guided Neuromodulation in Treatment Resistant Depression","ALIGN","Inclusion Criteria:\n\n* Age 18-65 of any sex, gender identity, ethnicity and socioeconomic status\n* Currently experiencing a major depressive episode as defined by DSM-5-TR criteria and confirmed by a study physician\n* Presenting with at least moderate symptom severity (MADRS ≥ 20)\n* Meeting criteria for treatment-resistant depression (TRD), defined as non-response to at least two adequate antidepressant trials\n* Neuromodulation-naïve (no past rTMS or electroconvulsive therapy)\n* Able to provide informed consent\n* Available for the 15-week intervention and willing to follow either a ketogenic or Canadian Food Guide-aligned diet\n\nExclusion Criteria:\n\n* Medical\u002Fpsychiatric co-morbidities that prevent participation in the study or where depression is not the primary psychiatric symptom of concern\n* History of epilepsy, stroke, or major neurological conditions, psychosis, or substance dependence within the last 6 months\n* Physical or cognitive disability interfering with participation\n* Females who are pregnant (self-report or via blood work), nursing, or planning a pregnancy during the timespan of the study BMI \\\u003C 20 kg\u002Fm²\n* Suicide attempts in the past 12 months\n* Active suicidal intent as confirmed by study psychiatrist\n* Active eating disorder in the past 12 months\n* Currently following a KD\n* Habitual low-carb diet in the past 6 months\n* GI disorders or food allergies incompatible with dietary protocols\n* Alcohol use \\>3 drinks\u002Fday or \\>14\u002Fweek\n* Use of anticonvulsants (benzodiazepines with a dose of \\\u003C2 lorazepam equivalents will be permitted), GABA agonists, or medications reducing TMS efficacy\n* Serious medical illness\n* Contraindications to MRI\n* Unwillingness to perform daily finger-stick testing","ALL","18 Years","65 Years",{"count":73,"type":74},60,"ESTIMATED","INTERVENTIONAL",[77],"NA","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.\n\nSpecifically, the study aims to determine whether the combined intervention:\n\n1. Reduces depressive symptoms\n2. Increases circulating ketone levels\n3. Is feasible and tolerable during accelerated iTBS treatment\n\nParticipants 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.",[80,81],"Major Depressive Disorder (MDD)","Treatment Resistant Depression (TRD)",[83,84,85,86,87,9,88,89,90,91,92,93,94,95],"Major Depressive Disorder","MDD","TRD","TMS","Glucose Control","Metabolic Health","Transcranial Magnetic Stimulation","iTBS","Dietary Intervention","Metabolic Psychiatry","MRS","fMRI","Intermittent Theta-Burst Stimulation","NOT_YET_RECRUITING","2026-02-03",{"date":99,"type":100},"2026-02-05","ACTUAL",{"date":102,"type":74},"2026-04-01",{"date":104,"type":74},"2027-10-01",{"name":5,"class":6},1]