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Exercise to Augment TMS in Those With Treatment Resistant Depression

Primary Purpose

Treatment Resistant Depression

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Aerobic Exercise
Video Watching
Sponsored by
Butler Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment Resistant Depression focused on measuring Aerobic Exercise, Transcranial Magnetic Stimulation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Butler Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Aerobic Exercise

Video Condition

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Intervention Acceptability
Percentage of participants approached for the study who agree to participate
Feasibility of Intervention
Percentage of sessions attended (out of a possible 30 sessions)

Secondary Outcome Measures

Resting state motor thresholds
A measure of corticolspinal excitation
short-interval intracortical inhibition (SICI)
A measure of GABAa channel activity
short-interval intracortical facilitation (SICF)
A reflection of glutamatergic tone uninhibited by GABA interneurons

Full Information

First Posted
June 12, 2023
Last Updated
October 5, 2023
Sponsor
Butler Hospital
Collaborators
National Institute of General Medical Sciences (NIGMS)
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1. Study Identification

Unique Protocol Identification Number
NCT05913401
Brief Title
Exercise to Augment TMS in Those With Treatment Resistant Depression
Official Title
Aerobic Exercise to Augment the Plasticity Effect of rTMS in Patients With Treatment-resistant Depression
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2023 (Anticipated)
Primary Completion Date
August 30, 2024 (Anticipated)
Study Completion Date
January 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Butler Hospital
Collaborators
National Institute of General Medical Sciences (NIGMS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Depression
Keywords
Aerobic Exercise, Transcranial Magnetic Stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Aerobic Exercise
Arm Type
Experimental
Arm Description
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.
Arm Title
Video Condition
Arm Type
Other
Arm Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Aerobic Exercise
Intervention Description
20 minutes of supervised aerobic exercise on a treadmill prior to each TMS session
Intervention Type
Behavioral
Intervention Name(s)
Video Watching
Intervention Description
20 minutes of watching documentaries or educational videos prior to each TMS session
Primary Outcome Measure Information:
Title
Intervention Acceptability
Description
Percentage of participants approached for the study who agree to participate
Time Frame
Baseline
Title
Feasibility of Intervention
Description
Percentage of sessions attended (out of a possible 30 sessions)
Time Frame
6-weeks
Secondary Outcome Measure Information:
Title
Resting state motor thresholds
Description
A measure of corticolspinal excitation
Time Frame
6-weeks
Title
short-interval intracortical inhibition (SICI)
Description
A measure of GABAa channel activity
Time Frame
6-weeks
Title
short-interval intracortical facilitation (SICF)
Description
A reflection of glutamatergic tone uninhibited by GABA interneurons
Time Frame
6-weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Butler Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Data will be made available to other researchers upon request.

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Exercise to Augment TMS in Those With Treatment Resistant Depression

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