StrokeRESTORATIONNCT07050355
Combining rTMS & Aerobic Exercise to Treat Depression and Improve Post-Stroke Walking
A study testing rTMS and AEx in people with Stroke and Depression - Major Depressive Disorder, run by Medical University of South Carolina at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Stroke, Depression - Major Depressive Disorder, Walking Impairment
- What is being tested?
- rTMS and AEx
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Nov 2024to 31 Aug 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Chris Gregory, PhD, 843-792-1078, gregoryc@musc.edu
Catherine Vandewrwerker, PhD, PT, vanderwe@musc.edu
- Recruiting
Duke University School of Medicine
Durham, North Carolina, 27710
Wayne Feng, MD, wayne.feng@duke.edu
About this study
Official title: Combining rTMS & Aerobic Exercise to Treat Depression and Improve Post-Stroke Walking (RESTORATION)
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.
Read the 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.
- Being tested
- rTMS, AEx
- Keywords
- stroke, rehabilitation, neuromodulation, TMS, walking, exercise
- Medical subject headings
- Stroke, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
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.
AExBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| rTMS | Active comparator | repetitive transcranial magnetic stimulation Receives: Device: rTMS |
| AEx | Active comparator | treadmill aerobic exercise Receives: Behavioral: AEx |
| rTMS + AEx | Experimental | combination of repetitive transcranial magnetic stimulation and treadmill aerobic exercise Receives: Device: rTMS; Behavioral: AEx |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of depressive symptoms
The Hamilton Depression Rating Scale (HAM-D17) is the gold-standard for clinical trial outcomes and samples a broad array of depressive symptoms. Critically, the rater administering the HAM-D17 will be clinically trained and will blinded to all other aspects of the study. For this trial, depression severity will be classified as moderate (HAM-D17 = 14-19) or severe (HAM-D = 20-25) for the purpose of stratification and diagnosed upon enrollment using the Structured Clinical Interview for Depression according to the Diagnostic \& Statistical Manual of Mental Disorders, 5th Edition (DSM-V).
Measured: baseline, after 2,4,6,8,10 and 12 weeks of treatment
Secondary outcomes (3)
six-minute walk test
Distance walked in 6 minutes
Measured: baseline, after 2,4,6,8,10 and 12 weeks of treatment
Step activity monitoring
Daily step count
Measured: baseline, after 2,4,6,8,10 and 12 weeks of treatment
Stroke Impact Scale
Assesses multiple domains of stroke recovery on a scale from 0 to 100, including strength, hand function, activities of daily living and instrumental activities of daily living, mobility, communication, emotion, memory and thinking, and participation, with higher scores representing better recovery
Measured: baseline, after 2,4,6,8,10 and 12 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2025
- Study start1 Nov 2024
- Primary completion31 Aug 2029 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Duke University
- Responsible party
- Principal investigator, Chris Gregory, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07050355
- Sponsor's protocol ID
- Pro00137804
- Other IDs
- R01HD113299
- Acronym
- RESTORATION
- Status last verified
- Aug 2026
- First submitted
- 3 Apr 2025
- Last updated
- 4 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: Unknown at this time
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining rTMS & Aerobic Exercise to Treat Depression and Improve Post-Stroke Walking (RESTORATION)
- ClinicalTrials.gov ID
- NCT07050355
- Acronym / sponsor ID
- RESTORATION / Pro00137804
- Keywords
- stroke, rehabilitation, neuromodulation, TMS, walking, exercise
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Duke University
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 31 Aug 2029 (estimated)
- Study completion
- 31 Aug 2029 (estimated)
- First posted
- 3 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| rTMS | Active comparator | Device: rTMSrepetitive transcranial magnetic stimulation |
| AEx | Active comparator | Behavioral: AExtreadmill aerobic exercise |
| rTMS + AEx | Experimental | Device: rTMS, Behavioral: AExcombination of repetitive transcranial magnetic stimulation and treadmill aerobic exercise |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rTMSSubjects 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. | Device | rTMS, rTMS + AEx |
| AExThe 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. | Behavioural | AEx, rTMS + AEx |
Primary outcome
Severity of depressive symptoms
Time frame: baseline, after 2,4,6,8,10 and 12 weeks of treatment
The Hamilton Depression Rating Scale (HAM-D17) is the gold-standard for clinical trial outcomes and samples a broad array of depressive symptoms. Critically, the rater administering the HAM-D17 will be clinically trained and will blinded to all other aspects of the study. For this trial, depression severity will be classified as moderate (HAM-D17 = 14-19) or severe (HAM-D = 20-25) for the purpose of stratification and diagnosed upon enrollment using the Structured Clinical Interview for Depression according to the Diagnostic \& Statistical Manual of Mental Disorders, 5th Edition (DSM-V).
3 secondary outcomes
six-minute walk test
Time frame: baseline, after 2,4,6,8,10 and 12 weeks of treatment
Step activity monitoring
Time frame: baseline, after 2,4,6,8,10 and 12 weeks of treatment
Stroke Impact Scale
Time frame: baseline, after 2,4,6,8,10 and 12 weeks of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2026.
- Individual participant dataSharing planned: Undecided. Unknown at this time
Related trials for Stroke
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ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
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Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
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Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS and AEx in people with Stroke and Depression - Major Depressive Disorder, run by Medical University of South Carolina at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chris Gregory, PhD ((843)792-1078, gregoryc@musc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severity of depressive symptoms (time frame: baseline, after 2,4,6,8,10 and 12 weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2026.