Ketogenic Diet and Neuromodulation in Treatment Resistant Depression

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

NCT Number	NCT07376018
Lead Sponsor	Sunnybrook Health Sciences Centre Collaborators: Baszucki Group
Conditions	Major Depressive Disorder (MDD), Treatment Resistant Depression (TRD)
Enrollment	60 participants
Start Date	2026-08
Primary Completion	2028-01 (estimated)
Study Completion	2028-01 (estimated)
Updated on ClinicalTrials.gov	2026-08-07