Stroke
Conditions
Brief summary
This project will assess the effects of aerobic exercise training (AET), repetitive transcranial magnetic stimulation (rTMS) or their combination on depressive severity as well as locomotor function in persons with post-stroke depression (PSD). Both AET and rTMS are established stand-alone treatments for non-stroke related depression, though neither has been adequately studied post-stroke. Furthermore, substantive research indicates that AET improves post-stroke locomotor function, thus offering a novel approach for treating PSD as well as an established vehicle to study the effects of PSD on response to rehabilitation. The purpose of this project is to determine the impact of AET, rTMS and their combination (AET+rTMS) treatments on post-stroke depressive symptoms and locomotor function so as to guide the development of a future clinical trial. A total of 40 depressed post-stroke subjects will be randomly assigned to one of four groups 1) AET; 2) rTMS; 3) combined AET and rTMS (AET+rTMS) or 4) control (sham rTMS) group (n=10 per condition; equally distributed with mild and moderate MDD). Further, an additional 10 non-depressed post-stroke subjects will complete 8 weeks of AET so as to allow us to determine the effects of PSD on response to training (Aim 2). Training (AET, rTMS and AET+rTMS) will take place over an 8-week period, three times per week on non-consecutive days. Measures of depression (HRSD17) as well as self-selected walking speed (SSWS) will be performed prior to the initial treatment session of each week as well as 8 weeks following cessation of treatment. Additional measures of locomotor function (walking endurance and amount of daily community stepping) will be assessed prior to training (pre), following 4 weeks of training (mid), upon completion of 8 weeks of training (post) as well as 8 weeks following cessation of training (follow-up), allowing determination of the efficacy (and persistence) of training on these outcomes.
Interventions
BEHAVIORALAerobic exercise
treadmill aerobic exercise; 3 sessions per week, 40 minutes per session
OTHERRepetitive transcranial magnetic stimulation
Repeated non-invasive brain stimulation to the left dorsolateral prefrontal cortex.
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. age 50-70 2. stroke within the past 6 to 60 months, 3. major depressive disorder (PHQ-9 \> 10) and diagnosed using the Structured Clinical Interview for Depression (SCID) according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), 4. residual paresis in the lower extremity (Fugl-Meyer LE motor score \<34), 5. ability to walk without assistance and without an AFO on the treadmill ≥ 30 seconds at speeds ranging from 0.2-0.8 m/s, 6. no antidepressant medications or clinically able to discontinue medications, 7. HRSD question #9 regarding suicide \<2, 8. provision of informed consent. In addition, all subjects who meet criteria for the training portion must complete an exercise tolerance test and be cleared for participation by the study cardiologist.
Exclusion criteria
1. Unable to ambulate at least 150 feet prior to stroke, or experienced intermittent claudication while walking; 2. history of congestive heart failure, unstable cardiac arrhythmias, hypertrophic cardiomyopathy, severe aortic stenosis, angina or dyspnea at rest or during ADL's; 3. History of oxygen dependence; 4. Preexisting neurological disorders, dementia or previous stroke; 5. History of major head trauma; 6. Legal blindness or severe visual impairment; 7. history of psychosis or other Axis I disorder that is primary; 8. Life expectancy \<1 yr.; 9. Severe arthritis or other problems that limit passive range of motion; 10. History of DVT or pulmonary embolism within 6 months; 11. Uncontrolled diabetes with recent weight loss, diabetic coma, or frequent insulin reactions; 12. Severe hypertension with systolic \>200 mmHg and diastolic \>110 mmHg at rest; 13. attempt of suicide in the last 2 years or at suicidal risk assessed by SCID interview; 14. Previous or current enrollment in a clinical trial to enhance motor recovery; 15. currently exercising ≥ 2 times per week (≥20 minutes); 16. Presence of non-MR compatible implants, pregnancy or severe claustrophobia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Post Training in Hamilton Rating Scale for Depression | assessed at baseline and weekly throughout the 8 week intervention. Change from baseline to week 8 reported as primary outcome | The Hamilton Rating Scale for Depression is a clinician-administered depression assessment scale containing 17 items pertaining to symptoms of depression experienced over the past week. A total score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a total score of 20 or higher indicates at least moderate severity depression. Score range 0-58. Higher total scores indicate higher levels of depression, while a score of 0 would indicate no depressive symptoms. |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline to Week 8 in Self-selected Walking Speed | assessed at baseline as well as weekly throughout the 8 week intervention. Change from baseline to week 8 reported as outcome |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aerobic Exercise Treadmill aerobic exercise
Aerobic exercise: treadmill aerobic exercise; 3 sessions per week, 40 minutes per session | 4 |
| rTMS repetitive transcranial magnetic stimulation
Repetitive transcranial magnetic stimulation: Repeated non-invasive brain stimulation to the left dorsolateral prefrontal cortex. | 6 |
| AET+rTMS Combined aerobic exercise and rTMS
Aerobic exercise: treadmill aerobic exercise; 3 sessions per week, 40 minutes per session
Repetitive transcranial magnetic stimulation: Repeated non-invasive brain stimulation to the left dorsolateral prefrontal cortex. | 6 |
| Sham Sham rTMS
Repetitive transcranial magnetic stimulation: Repeated non-invasive brain stimulation to the left dorsolateral prefrontal cortex. | 7 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | move out of area | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Aerobic Exercise | rTMS | AET+rTMS | Sham | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 3 Participants | 2 Participants | 1 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 4 Participants | 6 Participants | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 5 Participants | 3 Participants | 4 Participants | 13 Participants |
| Region of Enrollment United States | 4 participants | 6 participants | 6 participants | 7 participants | 23 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 1 / 4 | 0 / 6 | 1 / 6 | 0 / 7 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 7 |
Outcome results
Primary
Change From Baseline to Post Training in Hamilton Rating Scale for Depression
The Hamilton Rating Scale for Depression is a clinician-administered depression assessment scale containing 17 items pertaining to symptoms of depression experienced over the past week. A total score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a total score of 20 or higher indicates at least moderate severity depression. Score range 0-58. Higher total scores indicate higher levels of depression, while a score of 0 would indicate no depressive symptoms.
Time frame: assessed at baseline and weekly throughout the 8 week intervention. Change from baseline to week 8 reported as primary outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aerobic Exercise | Change From Baseline to Post Training in Hamilton Rating Scale for Depression | -2.75 units on a scale | Standard Deviation 4.5 |
| rTMS | Change From Baseline to Post Training in Hamilton Rating Scale for Depression | -7.5 units on a scale | Standard Deviation 5.46 |
| AET+rTMS | Change From Baseline to Post Training in Hamilton Rating Scale for Depression | -7.83 units on a scale | Standard Deviation 4.49 |
| Sham | Change From Baseline to Post Training in Hamilton Rating Scale for Depression | -2.29 units on a scale | Standard Deviation 2.63 |
Secondary
Change From Baseline to Week 8 in Self-selected Walking Speed
Time frame: assessed at baseline as well as weekly throughout the 8 week intervention. Change from baseline to week 8 reported as outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aerobic Exercise | Change From Baseline to Week 8 in Self-selected Walking Speed | 8.2 centimeters per second | Standard Deviation 9.52 |
| rTMS | Change From Baseline to Week 8 in Self-selected Walking Speed | 7.7 centimeters per second | Standard Deviation 15.43 |
| AET+rTMS | Change From Baseline to Week 8 in Self-selected Walking Speed | 30.65 centimeters per second | Standard Deviation 20.24 |
| Sham | Change From Baseline to Week 8 in Self-selected Walking Speed | 2.19 centimeters per second | Standard Deviation 15.04 |