Combining rTMS & Aerobic Exercise to Treat Depression and Improve Post-Stroke Walking

NCT ID: NCT07050355

Last Updated: 2025-07-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2029-08-31

Brief Summary

Investigators primary aim is to carry out a two-site, randomized, double-blind, sham-controlled, phase II trial to systematically examine the potential for aerobic exercise (AEx) to enhance the anti-depressant benefits of rTMS in individuals with post-stroke depression (PSD).

Investigators propose to determine the efficacy of combining two known anti-depressant treatments shown to be effective in non-stroke depression, aerobic exercise (AEx) and repetitive transcranial magnetic stimulation (rTMS), on post-stroke depressive symptoms. This project is based on the idea that depression negatively affects the potential for the brain to adapt in response to treatment such that rehabilitation may not produce the same changes that it does in non-depressed individuals. Investigators believe that effective treatment for PSD will result in a virtuous cycle whereby reducing depression enhances response to rehabilitation, thereby facilitating functional gains. That is, effectively treating depression will enable individuals to better recover from stroke.

Detailed Description

This project will determine whether aerobic exercise enhances the anti-depressant benefits rTMS in individuals with PSD through a two-site, prospective, randomized trial. Over a five-year period, 96 subjects (12-60 months post-stroke) will be assigned to complete 12 weeks of treatment with rTMS, treadmill AEx or both (i.e., rTMS+AEx). Treatments will take place three times per week on non-consecutive days. Assessments of depression (HAM-D17) and walking capacity (6MWT) will be performed at two-week intervals throughout treatment as well as 12- and 24-weeks following cessation of treatment, allowing determination of the efficacy (and persistence) of training on these outcomes. Secondary outcomes will include measures of community walking (steps per day) and quality of life (Stroke Impact Scale) collected pre-, mid- and post-training, as well as at the follow-up time points. Last, investigators will explore potential biomarkers of response via assessment of PAS-induced neuroplastic potential and MR imaging to identify changes in cortical grey matter thickness.

Conditions

Stroke; Depression - Major Depressive Disorder; Walking Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

rTMS

repetitive transcranial magnetic stimulation

Group Type: ACTIVE_COMPARATOR

rTMS

Intervention Type: DEVICE

Subjects will undergo rTMS to the left dorsolateral prefrontal region as a treatment for depression. Treatment will be performed three times per week for 12 weeks (36 sessions) . We will use a standard resting motor threshold (rMT) determination from unaffected abductor pollicis brevis. Treatments will be delivered at the EEG coordinate for F3 (approximating the left DLPFC) and will be found using the Beam-F3 method. A total of 5000 pulses/session will be delivered at 10Hz with an intensity of 120% of rMT.

AEx

treadmill aerobic exercise

Group Type: ACTIVE_COMPARATOR

AEx

Intervention Type: BEHAVIORAL

The goal of AEx will be 20 minutes of continuous walking at an intensity of \~70% of heart rate reserve (HRR calculated via the Karvonen method). The desired intensity will be achieved by a combination of increasing treadmill speed and incline. Rest breaks will be allowed as needed during training with the goal of progressing to 20 minutes of continuous walking.

rTMS + AEx

combination of repetitive transcranial magnetic stimulation and treadmill aerobic exercise

Group Type: EXPERIMENTAL

rTMS

Intervention Type: DEVICE

Subjects will undergo rTMS to the left dorsolateral prefrontal region as a treatment for depression. Treatment will be performed three times per week for 12 weeks (36 sessions) . We will use a standard resting motor threshold (rMT) determination from unaffected abductor pollicis brevis. Treatments will be delivered at the EEG coordinate for F3 (approximating the left DLPFC) and will be found using the Beam-F3 method. A total of 5000 pulses/session will be delivered at 10Hz with an intensity of 120% of rMT.

AEx

Intervention Type: BEHAVIORAL

The goal of AEx will be 20 minutes of continuous walking at an intensity of \~70% of heart rate reserve (HRR calculated via the Karvonen method). The desired intensity will be achieved by a combination of increasing treadmill speed and incline. Rest breaks will be allowed as needed during training with the goal of progressing to 20 minutes of continuous walking.

Interventions

rTMS

Subjects will undergo rTMS to the left dorsolateral prefrontal region as a treatment for depression. Treatment will be performed three times per week for 12 weeks (36 sessions) . We will use a standard resting motor threshold (rMT) determination from unaffected abductor pollicis brevis. Treatments will be delivered at the EEG coordinate for F3 (approximating the left DLPFC) and will be found using the Beam-F3 method. A total of 5000 pulses/session will be delivered at 10Hz with an intensity of 120% of rMT.

Intervention Type: DEVICE

AEx

The goal of AEx will be 20 minutes of continuous walking at an intensity of \~70% of heart rate reserve (HRR calculated via the Karvonen method). The desired intensity will be achieved by a combination of increasing treadmill speed and incline. Rest breaks will be allowed as needed during training with the goal of progressing to 20 minutes of continuous walking.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• age 21-70
• stroke within the past 12 to 60 months
• screen positive for probable major depressive disorder (PHQ-9 > 10) and HAM-D17 ≥ 14
• residual paresis in the lower extremity (Fugl-Meyer LE motor score <34)
• ability to walk without assistance and without an AFO at speeds ranging from 0.2-1.0 m/s
• not currently on antidepressant medications or no changes in antidepressant dosage in the last 4 weeks and clinically stable
• HAM-D17 question #9 regarding suicide <2
• provision of informed consent.

Exclusion Criteria

• unable to ambulate at least 150 feet prior to stroke, or experienced intermittent claudication while walking
• history of congestive heart failure, unstable cardiac arrhythmias, hypertrophic cardiomyopathy, severe aortic stenosis, angina or dyspnea at rest or during ADL's
• history of COPD or oxygen dependence
• history of traumatic brain injury
• blindness or severe visual impairment
• history of psychosis or other Axis I disorder that is primary
• life expectancy <1 yr.
• severe arthritis or problems that limit participation in testing or training
• history of DVT or pulmonary embolism within 6 months
• uncontrolled diabetes with recent weight loss, diabetic coma, or frequent insulin reactions
• severe hypertension with systolic >200 mmHg and diastolic >110 mmHg at rest
• attempt of suicide in the last 2 years or suicidal risk assessed by SCID
• history of seizures or currently prescribed anti-seizure medications
• current enrollment in a trial to enhance motor recovery
• currently participating in behavioral treatment for depression
• currently exercising ≥ 2 times per week (≥20 minutes)
• contraindications to TMS
• pregnancy or other contraindications to MRI.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Chris Gregory

Professor-Faculty

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Duke University School of Medicine

Durham, North Carolina, United States

Site Status: ACTIVE_NOT_RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Chris Gregory, PhD

Role: CONTACT

gregoryc@musc.edu

(843)792-1078

Facility Contacts

Chris Gregory, PhD

Role: primary

gregoryc@musc.edu

843-792-1078

Catherine Vandewrwerker, PhD, PT

Role: backup

vanderwe@musc.edu

Other Identifiers

R01HD113299

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00137804

Identifier Type: -

Identifier Source: org_study_id