Exercise priming before rTMS (iTBS) for difficult-to-treat depression

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a randomized, two-arm pilot feasibility trial enrolling physically inactive adults with treatment-resistant major depressive disorder. One group completes 4 weeks of moderate-to-vigorous exercise (≈1 hour, 3x/week) followed by 6 weeks of iTBS with ongoing exercise, while the control group has 4 weeks of stable treatment followed by 6 weeks of iTBS alone. The priming phase aims to increase fitness and neuroplasticity to improve responsiveness to iTBS, and the synergetic phase integrates neuromodulation with maintained exercise. Feasibility measures and changes in depressive symptoms will be collected to inform larger future trials.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Are between 18-75 years old.
2. Able to provide voluntary informed consent.
3. Diagnosis of MDD or Persistent Depressive Disorder, without psychotic features, confirmed by MINI for DSM-5.
4. Depressive symptoms have not improved after ≥ 1 adequate antidepressant trial in the current episode (i.e., difficult-to-treat MDD), based on the Antidepressant Treatment History Form (ATHF).
5. Baseline score of ≥15 on the HRSD-17.
6. No change in psychotropic medications or psychotherapy regimen at least 4 weeks prior to entering the trial
7. Physically inactive as per the International Physical Activity Questionnaire - Short Form (IPAQ-SF).
8. Able to engage in structured exercise as per the Get Active Questionnaire (GAQ).
9. Able to adhere to the proposed treatment schedule.

Exclusion Criteria:

1. Diagnosis of bipolar I or II disorder, based on DSM-5 criteria.
2. Current or past (\<3 months) substance (excluding caffeine or nicotine) or alcohol abuse/dependence, as defined in DSM-5 criteria.
3. Current use of illegal substances.
4. Current use of cannabis.
5. Concomitant major unstable medical or neurologic illness (e.g., uncontrolled diabetes or renal dysfunction).
6. Organic cause of the depressive symptoms (e.g. thyroid dysfunctions), determined by the referring physician.
7. Acute suicidality or threat to life from self-neglect.
8. Pregnant or breastfeeding, or thinking of becoming pregnant during course of treatment.
9. Contraindication for TMS and MRI (e.g., personal history of epilepsy or seizure, metallic head implant, pacemaker), confirmed by TMS Adult Safety Scale (TASS) and MRI pre-screener.
10. Unwilling to maintain current psychotropic medication and/or psychotherapy regimen for the four weeks prior to and for the duration of the study.
11. Taking more than 1 mg/day of lorazepam or equivalent.
12. Any other condition that, in the opinion of the investigators which would adversely affect the participant's ability to complete the study.
13. Physically active: performing exercise and/or physical activity levels meeting the cut-off for "minimally active" on the IPAQ-SF.

Where it's running

• Royal Ottawa Mental Health Centre
  Ottawa, Ontario, Canada Recruiting

Study contacts

• Principal investigator: Sara Tremblay, PhD — Royal Ottawa Mental Health Centre
• Study coordinator: Stacey Shim, MSc
• Email: stacey.shim@theroyal.ca
• Phone: 613-722-6521

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.