RECRUITINGINTERVENTIONAL

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

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

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 willing to sign a consent form. Who Should NOT Join This Trial: - 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. Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

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.

Treatments Being Tested

DEVICE

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.

BEHAVIORAL

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.

Locations (2)

Duke University School of Medicine

Durham, North Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States