Feasibility Trial of Exercise as a Priming Strategy for rTMS Treatment in Difficult-to-Treat Depression

NCT06773949 | Recruiting

• 1 other identifier: 0227
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to collect feasibility data on combining structured exercise aimed to improve physical fitness, and intermittent TBS (iTBS) in treating individuals diagnosed with difficult-to-treat depression who are physically inactive. By conducting this trial, we will compare the therapeutic benefits of the combined approach against the standard treatment of iTBS alone (without exercise). These findings will be used to inform future large-scale projects in which we will investigate, in a larger sample size, whether structured exercise aimed to improve fitness as recommended by most public exercise guidelines (i.e., ≥3x/week, moderate-to-vigorous intensity) serves as an active ingredient that amplifies the effectiveness of iTBS. Ultimately, the insights gained from this study will be valuable for clinicians seeking to alleviate depressive symptoms in MDD through neuromodulation techniques such as iTBS.

Conditions

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

Keywords

iTBS; rTMS; Exercise; Physical inactivity

Outcome Measures

Primary Outcomes (2)

• Assessing feasibility on combining structured exercise and intermittent Theta Burst Stimulation (iTBS) in participants with treatment-resistant depression (TRD)

  Feasibility outcomes are crucial metrics that will guide the refinement of our protocols, thereby enhancing our preparedness for future design endeavors. These will include: 1) recruitment, 2) adherence, 3) compliance, 4) retention, 5) satisfaction, and 6) adverse events.

  Assessed at the end of the study once all participants have completed the study.

• Compare the effects on clinical response of exercise on enhancing iTBS treatment efficacy vs. iTBS alone

  Clinical response will be defined as a ≥ 50% reduction in the 17-item Grid Hamilton Rating Scale for Depression (Grid-HRSD-17). The Grid HRSD is a clinician-rated instrument with seventeen items used to measure the severity of depressive episodes. The overall score ranges from 0 to 52, where scores of 0 to 7 are considered as being normal, 8 to 16 suggest mild depression, 17 to 23 moderate depression, and scores ≥ 24 indicate severe depression.

  Administered at screening, before iTBS treatment course (week 4), at the end of the treatment course (week 10), then at the 6-week follow-up (week 16)

Secondary Outcomes (7)

• Change in self-reported depression symptoms as measured by Beck Depression Inventory (BDI-II).

  Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)

• Change in self-reported anxiety symptoms as measured by Beck Anxiety Inventory (BAI)

  Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)

• Change in self-reported suicidal thoughts symptoms as measured by Beck Scale for Suicidal Ideation (BSS)

  Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)

• Change in self-reported hopelessness as measured by State Hope Scale (SHS)

  Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)

• Change in neuroplasticity as measured by neurophysiology (TMS) and MRI (Arterial Spin Labelling measures of brain blood flow)

  Administered at pre-assessment (baseline), before iTBS treatment course (week 4), end of iTBS treatment course (week 10)

Other Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events

  Daily Monday-Friday throughout study (16 weeks).

• Side Effects

  Daily Monday-Friday throughout study (16 weeks).

Study Arms (2)

Intervention Group

EXPERIMENTAL

4-weeks of exercise (moderate-to-vigorous intensity) followed by 6 weeks of iTBS combined with exercise.

Device: Theta burst stimulation

Standard Group

OTHER

Standard care of 4 weeks of stable treatment (i.e. no changes to antidepressant regimen or physical activity) followed by 6 weeks of iTBS alone.

Device: Theta burst stimulation

Interventions

Theta burst stimulation DEVICE

Cool B70 cooled-coil (left DLPFC) with X100 MagPro rTMS Device (Magventure A/S, Farum, Denmark)

Also known as: rTMS

Intervention Group; Standard Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are between 18-75 years old.
• Able to provide voluntary informed consent.
• Diagnosis of MDD or Persistent Depressive Disorder, without psychotic features, confirmed by MINI for DSM-5.
• 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).
• Baseline score of ≥15 on the HRSD-17.
• No change in psychotropic medications or psychotherapy regimen at least 4 weeks prior to entering the trial
• Physically inactive as per the International Physical Activity Questionnaire - Short Form (IPAQ-SF).
• Able to engage in structured exercise as per the Get Active Questionnaire (GAQ).
• Able to adhere to the proposed treatment schedule.

You may not qualify if:

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

Sponsors & Collaborators

• The Royal Ottawa Mental Health Centre: lead
• University of Ottawa: collaborator

Study Sites (1)

Royal Ottawa Mental Health Centre

Ottawa, Ontario, k1z 7k4, Canada

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Motor Activity; Sedentary Behavior

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavior

Study Officials

• Sara Tremblay, PhD

  Royal Ottawa Mental Health Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stacey Shim, MSc

CONTACT

613-722-6521; stacey.shim@theroyal.ca

Emma Cummings, BSc

CONTACT

6137226521; emma.cummings@theroyal.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientist

Study Record Dates

• First Submitted: January 8, 2025
• First Posted: January 14, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: De-identified data may become available (upon request) when the study is completed and published (anticipated time frame: the year of 2027)
• Access Criteria: De-identified data will be accessible only through the permission of the lead research scientist. All requests must be made and accepted by her.

Locations

CA (1)