Combining rTMS and aerobic exercise to reduce depression and improve walking after stroke

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

This study will try combining repetitive transcranial magnetic stimulation (rTMS) with treadmill aerobic exercise to see if it reduces depression and improves walking in people 12–60 months after a stroke.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 21 Years to 70 Years
• Sex: All
• Sponsor: Medical University of South Carolina (other)
• Locations: 2 sites (Durham, North Carolina and 1 other locations)
• Trial ID: NCT07050355 on ClinicalTrials.gov

What this trial studies

This is a two-site, randomized, double-blind, sham-controlled phase II trial enrolling 96 participants 12–60 months after stroke to receive 12 weeks of treatment delivered three times per week. Participants will be assigned to receive rTMS, treadmill aerobic exercise (AEx), or the combination (rTMS+AEx) with symptom and function assessments every two weeks during treatment and at 12- and 24-week follow-ups. Primary outcomes are depressive symptoms (HAM-D17) and walking capacity (6MWT); secondary outcomes include community walking (steps/day) and quality of life (Stroke Impact Scale). The protocol also includes exploratory biomarker studies using PAS-induced plasticity testing and MRI measures of cortical grey matter thickness.

Who should consider this trial

Good fit: Adults aged 21–70 who had a stroke 12–60 months ago, screen positive for probable major depressive disorder (PHQ-9 >10 and HAM-D17 ≥14), have residual lower‑extremity weakness but can walk unassisted at 0.2–1.0 m/s, and are not changing antidepressant medications would be ideal candidates.

Not a fit: People with unstable cardiac or severe pulmonary disease, a history of traumatic brain injury or psychosis, severe visual impairment, inability to ambulate prior to stroke, or active high suicide risk are unlikely to benefit or may be excluded for safety.

Why it matters

Potential benefit: If successful, combining rTMS with aerobic exercise could reduce depressive symptoms and produce larger, more durable improvements in walking and daily function after stroke.

How similar studies have performed: rTMS and aerobic exercise each have evidence of antidepressant benefit in non-stroke populations and some small studies support rTMS in post-stroke depression, but the specific combination in PSD has not been widely tested.

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.

Where this trial is running

Durham, North Carolina and 1 other locations

• Duke University School of Medicine — Durham, North Carolina, United States (ACTIVE_NOT_RECRUITING)
• Medical University of South Carolina — Charleston, South Carolina, United States (RECRUITING)

Study contacts

• Study coordinator: Chris Gregory, PhD

Conditions: Stroke, Depression - Major Depressive Disorder, Walking Impairment, stroke, rehabilitation, neuromodulation, TMS, walking