About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Factorial
Treatments tested in this trial
rTMS
DeviceSubjects 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
BehavioralThe 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.
Treatment groups
Trial outcomes
Primary outcomes
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).
Secondary outcomes
six-minute walk test
Distance walked in 6 minutes
Step activity monitoring
Daily step count
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
Sponsors and contacts
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Medical University of South Carolina
Lead sponsor
National Institutes of Health (NIH)
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator
Duke University
Collaborator