Ketogenic Diet and Neuromodulation in Treatment Resistant Depression

Summary

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

Conditions

• Major Depressive Disorder (MDD)
• Treatment Resistant Depression (TRD)

Interventions

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.

BEHAVIORAL

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.

BEHAVIORAL

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.

Sponsors & Collaborators

• Baszucki Group

  collaborator UNKNOWN

• Sunnybrook Health Sciences Centre

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-31

Primary Completion

2028-01-31

Completion

2028-01-31

Countries

• Canada

Study Locations