Recruiting

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

Sponsor:

Medical University of South Carolina

Code:

NCT07050355

Conditions

Stroke

Depression - Major Depressive Disorder

Walking Impairment

Eligibility Criteria

Sex: All

Age: 21+

Healthy Volunteers: Not accepted

Interventions

rTMS

AEx

Study Details

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.

Conditions

Stroke

Depression - Major Depressive Disorder

Walking Impairment

Study ID

NCT07050355

Start date

Nov 1, 2024

Status verified date

Aug, 2026

Completion date

Aug 31, 2029

Anticipated

Primary completion date

Aug 31, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 21+

Healthy Volunteers: Not accepted

Inclusion criteria:

age >21
stroke at least 12 months prior
screen positive for depressive symptoms (PHQ-9 > 5) and HAM-D17 ≥ 12
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. I
All subjects who screen for major depressive disorder will be formally diagnosed by the project psychiatrist at each site using the Structured Clinical Interview for DSM5 (SCID-5).
All subjects who meet criteria for the training portion must complete an exercise tolerance test and be cleared for participation by the study physician.

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.

Study Design

Enrollment

96 participants

Anticipated

Allocation

Randomized

Intervention Model

Factorial

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: rTMS

repetitive transcranial magnetic stimulation

active comparator: AEx

treadmill aerobic exercise

experimental: rTMS + AEx

combination of repetitive transcranial magnetic stimulation and treadmill aerobic exercise

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.

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.

Primary outcome measure

Severity of depressive symptoms [ Time Frame: baseline, after 2,4,6,8,10 and 12 weeks of treatment ]

Central Contacts and Locations

Central contacts

Chris Gregory, PhD

(843)792-1078 gregoryc@musc.edu

Locations

Duke University School of Medicine

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Wayne Feng, MD

wayne.feng@duke.edu

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Chris Gregory, PhD

843-792-1078 gregoryc@musc.edu

Catherine Vandewrwerker, PhD, PT

vanderwe@musc.edu

More Information

Sponsor

Medical University of South Carolina

Last update posted

Aug 4, 2026

Last verified

Aug, 2026

Keywords

stroke
rehabilitation
neuromodulation
TMS
walking
exercise

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Medical University of South Carolina on 2026-08-04.