Exercise to Augment TMS in Those With Treatment Resistant Depression

June 1, 2026 updated by: Butler Hospital

Aerobic Exercise to Augment the Plasticity Effect of rTMS in Patients With Treatment-resistant Depression

Given the growing evidence that aerobic increases cortical excitability and promotes neuroplasticity, the scientific premise for its potential priming effect on the brain is strong. Combining AE with rTMS may produce a neural environment optimized for a robust physiological effect of rTMS, thereby leading to improved depression outcomes. With positive findings, this study would provide preliminary support for an innovative, safe and feasible approach for improving outcomes for this significant public health problem.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Depression is highly prevalent and a significant public health concern, resulting in tremendous economic and societal burden. With first-line treatments leaving the majority of patients with unremitted and impairing symptomatology, additional therapies to address treatment-resistant depression (TRD) are critical. One such approach that has received significant empirical attention is repetitive transcranial magnetic stimulation (rTMS). While effective in reducing depression, rTMS's efficacy is not without limits, with remission rates being less than 40%. Therefore, research focused on improving the efficacy of rTMS is timely and critical for decreasing the overall public health burden of TRD. A putative mechanism of the effect of rTMS on depression is through changes in electrophysiological properties of neurons leading to increases in long-term potentiation (LTP) necessary for neuroplasticity. In theory, it may be possible to improve rTMS outcomes by augmenting it with another non-pharmacological treatment known to influence neuroplasticity. One innovative possibility could be aerobic exercise (AE), as it has shown to result in increased neuroplasticity in both animal and human studies and is known to reduce depression. There are a number of neural effects of AE that could serve to prime the brain for rTMS including increased prefrontal oxygenation and increased brain-derived neurotropic factor (BDNF, involved in inducing LTP). Conceivably, bouts of AE just prior to rTMS sessions may create a neural environment that is broadly primed for the more focally delivered TMS, potentially increasing its effectiveness. To date, there have been no studies that have combined AE with rTMS. Therefore, the purpose of the proposed study is to conduct the first test of AE priming among treatment-resistant depressed individuals seeking rTMS treatment. We expect that AE will improve the efficacy of rTMS through changes in exercise-induced neuroplasticity via measurements of motor-evoked potential (MEP). Exercise studies have shown single bouts of aerobic activity can result in increased MEP amplitudes and chronic AE (i.e., multi-sessions) decreases resting motor thresholds (RMT; the lowest intensity of TMS that evokes a MEP), thereby increasing overall cortical excitability. For the proposed pilot study, we will recruit N=30 patients with treatment-resistant depression who are seeking rTMS treatment at Butler Hospital's TMS Clinic. Participants will be randomized to engage in one of two different activities just prior to their scheduled daily TMS treatments: 1) 20 minutes of supervised moderate-intensity AE on an on-site treadmill (n=15) OR 2) 20-minutes of watching an educational video (n=15) while sitting. To examine indicators of neuroplasticity, a TMS cortical excitability protocol (assessing plasticity through measuring MEPs generated by single and paired magnetic pulses) will be conducted at baseline (prior to initiating the course of rTMS) and then again after 30 rTMS treatment sessions. At these same timepoints, depression severity will be measured using the Inventory of Depressive Symptomatology-Self Report scale (IDS-SR). The feasibility and acceptability of the combined AE+TMS approach will also be examined to inform the design of a future larger trial.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Butler Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • adult outpatients (age 18 and above) who are already approved to receive standard TMS therapy through the Butler Hospital TMS clinic.
  • able to safely engage in moderate-intensity aerobic exercise (determined by a study physician)

Exclusion Criteria:

  • Currently pregnant or plans to become pregnant in the next 6 weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Aerobic Exercise
Exercise sessions will be 20 minutes of moderate-intensity aerobic exercise on a treadmill. A treadmill is located on D1A within the space shared by the Butler Hospital TMS Clinic and the COBRE-support Neuromodulation Research Facility. A research staff member will monitor their heart rate and blood pressure to ensure safety and that activity is occurring at a moderate intensity (i.e., 64-76% of age predicted maximal heart rate). Participants will be asked to rate their affect and rating of perceived exertion (RPE) during exercise sessions. Sessions will include a 5-min warm-up and a 5-min cool-down to ensure safe exercise procedures. Participants will be asked to answer questions about affect before, during, and after exercise. These sessions will be supervised (i.e., they provide onsite coverage) by an exercise physiologist or medical staff member (e.g., nurse or physician) to ensure safety.
Behavioral: Aerobic Exercise
20 minutes of supervised aerobic exercise on a treadmill prior to each TMS session
Other: Video Condition
In this condition, participants will be asked to sit and watch various documentaries or educational videos on topics NOT related to physical activity. These will last approximately 20 minutes and will occur before each TMS session.
Behavioral: Video Watching
20 minutes of watching documentaries or educational videos prior to each TMS session

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Intervention Acceptability
Time Frame: Baseline
Percentage of participants approached for the study who agree to participate
Baseline
Feasibility of Intervention
Time Frame: 6-weeks
Percentage of sessions attended (out of a possible 30 sessions)
6-weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Resting state motor thresholds
Time Frame: 6-weeks
A measure of corticolspinal excitation
6-weeks
short-interval intracortical inhibition (SICI)
Time Frame: 6-weeks
A measure of GABAa channel activity
6-weeks
short-interval intracortical facilitation (SICF)
Time Frame: 6-weeks
A reflection of glutamatergic tone uninhibited by GABA interneurons
6-weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Butler Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of General Medical Sciences (NIGMS)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 12, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 12, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 22, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2304-001
  • P20GM130452 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data will be made available to other researchers upon request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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