Ketogenic Diet and Neuromodulation for Depression

(ALIGN Trial)

SM
JD
Overseen ByJo Donguk, PhD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Are You a Good Fit for This Trial?

Adults aged 18-65 with treatment-resistant depression, who haven't responded to at least two antidepressant trials and have never had rTMS or electroconvulsive therapy. Participants must be able to consent, follow a specific diet for 15 weeks, and are currently experiencing a major depressive episode with moderate severity.

Inclusion Criteria

I am currently experiencing a major depressive episode.
My depression symptoms are moderate to severe.
I am between 18 and 65 years old.
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dietary Lead-in

Participants begin either a ketogenic diet or a Canadian Food Guide-aligned diet for a 3-week dietary lead-in period

3 weeks
1 visit (in-person) for dietitian counseling

Treatment

Participants undergo a course of personalized, accelerated iTBS while continuing their assigned diet. Clinical assessments, blood samples, and MRI scans are conducted.

9 weeks
Weekly visits (in-person) for iTBS and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

  • Accelerated Intermittent Theta Burst Stimulation (iTBS)
  • Ketogenic Diet

Trial Overview

The trial is testing if a ketogenic diet combined with personalized accelerated iTBS can reduce symptoms of depression more effectively than iTBS with a standard healthy diet. It includes dietary adjustments, iTBS sessions, clinical assessments, blood tests for metabolism, and MRI scans over the course of the study.

How Is the Trial Designed?

2

Treatment groups

Experimental Treatment

Active Control

Group I: Ketogenic DietExperimental Treatment1 Intervention
Group II: Canadian Food Guide-Aligned DietActive Control1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials
693
Recruited
1,569,000+

Baszucki Group

Collaborator