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Strokes are very common in the United States and occur more in the elderly. The number of strokes is likely to double in the next 50 years. Many stroke survivors are sedentary and have a poor dietary intake, which results in abnormalities in fuel utilization (eg carbohydrate versus fat). This study will examine the effects of dietary modification and treadmill training on fuel utilization and physical function. We will study skeletal muscle oxidative stress in chronic stroke patients and the ability to employ dietary modification and exercise training to reverse these abnormalities in this ethnically diverse population.
In acute stroke settings, it is known that energy imbalance is associated with poorer rehabilitation and functional outcomes, and importantly, increased risk of institutionalization. However, nutrition and eating habits of chronic stroke rehabilitative care have received very little consideration, especially if the survivor is living in a free living environment. Studies have shown deficiencies in energy and protein intake versus recommendations in chronic stroke survivors. Perry et al. found ~7% of chronic stroke survivors were at moderate and ~5% at high nutritional risk. Although little is known regarding total daily energy expenditure and dietary intake in chronic stroke, energy and macronutrient imbalance may have a profound impact on stroke recovery and risk of development of chronic disease and recurrent stroke by altering substrate oxidation and result in systemic and tissue level oxidative stress. Conversely, cardiovascular disease risk increases with excess calorie and fat intake and two-thirds of stroke survivors are overweight or obese. In obese, non-stroke populations, energy dense, high fat meals are associated with increases in plasma oxidative stress markers. Oxidative stress can lead to mitochondrial damage and abnormal accumulation of metabolite intermediates and lipid accumulation in non-adipose tissues, which can impair heart function, increasing CVD and stroke recurrence risk.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stretching (Control) | Other | Six months of stretching |
|
| Treadmill Exercise | Experimental | Six months of treadmill training |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treadmill Exercise | Behavioral | Training will be started conservatively with a goal of 15 minutes total duration at 40-50% HRR. Training target HR = %(HRmax - HRrest) + HRrest. HR max is defined as peak HR based on 2 maximal exercise tests at baseline. Individuals unable to walk continuously will exercise intermittently for several minutes as tolerated, with rest intervals, and advanced as tolerated with HR, blood pressure monitoring, and Borg Perceived Exertion to assess subjective cardiopulmonary exercise tolerance, as previously described. Treadmill training velocity will advance as tolerated by week 6 to a target intensity of 70-80% maximal HRR. Duration will similarly advance to a target of 30 minutes by week 6. Following week 6, the progressive training protocol will continue with attempts to increase velocity on a weekly basis and increase duration by 5 minutes bi-weekly to peak at 50 minutes. After week 6, the target HR goal will be 75-85% of HRR as tolerated by the subject. |
| Measure | Description | Time Frame |
|---|---|---|
| The Change in Total Daily Energy Expenditure | Subjects will wear an accelerometer activity monitor on their belt for 5 to 7 days to determine caloric expenditure in daily activities. | measured at baseline and following 6 months of treadmill training or stretching (control) |
| Measure | Description | Time Frame |
|---|---|---|
| The Change in Substrate Oxidation | After a 12 hour fast, economy of hemiparetic gait will be measured using open circuit spirometry during a standard constant load submaximal effort treadmill walking task at a pre-established gait velocity (60% of self-selected floor walking velocity). This slower walking velocity is selected because untrained subjects with stroke usually cannot maintain their self-selected walking pace, precluding steady state measures of oxygen consumption that defines gait economy. We will calculate the change in respiratory exchange ratio from rest to the final 3 minutes of a 10-minute walk under steady state oxygen consumption conditions (RER at 60%VO2peak-RER at rest). Subjects not achieving a plateau in VO2 will be re-tested at a lower velocity on a different date to eliminate potential confounding effects of fatigue on testing. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Monica C Serra, PhD | South Texas Health Care System, San Antonio, TX | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD | Baltimore | Maryland | 21201 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35839921 | Derived | Serra MC, Hafer-Macko CE, Robbins R, O'Connor JC, Ryan AS. Randomization to Treadmill Training Improves Physical and Metabolic Health in Association With Declines in Oxidative Stress in Stroke. Arch Phys Med Rehabil. 2022 Nov;103(11):2077-2084. doi: 10.1016/j.apmr.2022.06.011. Epub 2022 Jul 12. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Stretching (Control) | Six months of stretching Stretching (control): Stretch controls will be enrolled in supervised stretching program for 2 days/week for 1 hour sessions. The stretch program will focus on basic mobility skills, including balance, endurance, sit-to-stand, weight shifting, and truncal stability-coordination. Stretching will be done in groups up to 6 participants. Exercises will be performed in standing, seated, and lying positions. |
| FG001 | Treadmill Exercise | Six months of treadmill training Treadmill Exercise: Training will occur 3 days/week and will be started conservatively with a goal of 15 minutes total duration at 40-50% HRR. Training target HR = %(HRmax - HRrest) + HRrest. Individuals unable to walk continuously will exercise intermittently for several minutes as tolerated, with rest intervals, and advanced as tolerated with HR, blood pressure monitoring, and Borg Perceived Exertion to assess subjective cardiopulmonary exercise tolerance. Treadmill training velocity will advance as tolerated by week 6 to a target intensity of 70-80% maximal HRR. Duration will similarly advance to a target of 30 minutes by week 6. Following week 6, the progressive training protocol will continue with attempts to increase velocity on a weekly basis and increase duration by 5 minutes bi-weekly to peak at 50 minutes. After week 6, the target HR goal will be 75-85% of HRR as tolerated by the subject. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Stretching (Control) | Six months of stretching Stretching (control): Stretch controls will be enrolled in supervised stretching program for 2 days/week for 1 hour sessions. The stretch program will focus on basic mobility skills, including balance, endurance, sit-to-stand, weight shifting, and truncal stability-coordination. Stretching will be done in groups up to 6 participants. Exercises will be performed in standing, seated, and lying positions. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Change in Total Daily Energy Expenditure | Subjects will wear an accelerometer activity monitor on their belt for 5 to 7 days to determine caloric expenditure in daily activities. | Posted | Mean | Standard Deviation | change in kcal/day | measured at baseline and following 6 months of treadmill training or stretching (control) |
|
6 months from baseline
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stretching (Control) | Six months of stretching Stretching (control): Stretch controls will be enrolled in supervised stretching program for 2 days/week for 1 hour sessions. The stretch program will focus on basic mobility skills, including balance, endurance, sit-to-stand, weight shifting, leg strength, and truncal stability-coordination. Stretching will be done in groups up to 6 participants. Exercises will be performed in standing, seated, and lying positions. A log book on the stretching exercise participation and progression will be maintained and reviewed by the instructor with the participant at each session. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Recurrent stroke | Vascular disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Monica Serra | South Texas Veterans Health Care System | 210-617-5300 | 15313 | monica.serra@va.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 16, 2019 | Jan 13, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020521 | Stroke |
| D057185 | Sedentary Behavior |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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Subjects are randomized to either stretching or treadmill training.
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|
| Stretching (control) | Behavioral | Stretch controls will be enrolled in supervised stretching program for 2 days/week for 1 hour sessions. The stretch program will focus on basic mobility skills, including balance, endurance, sit-to-stand, weight shifting, leg strength, and truncal stability-coordination. Stretching will be done in groups up to 6 participants. Exercises will be performed in standing, seated, and lying positions. A log book on the stretching exercise participation and progression will be maintained and reviewed by the instructor with the participant at each session. |
|
| measured at baseline and following 6 months of treadmill training or stretching (control) |
| The Change in Circulating Nitrotyrosine | Plasma will be used to quantitate circulating nitrotyrosine concentrations | measured at baseline and following 6 months of treadmill training or stretching (control) |
| South Texas Health Care System, San Antonio, TX |
| San Antonio |
| Texas |
| 78229 |
| United States |
| BG001 | Treadmill Exercise | Six months of treadmill training Treadmill Exercise: Training will occur 3 days/week and will be started conservatively with a goal of 15 minutes total duration at 40-50% HRR. Training target HR = %(HRmax - HRrest) + HRrest. Individuals unable to walk continuously will exercise intermittently for several minutes as tolerated, with rest intervals, and advanced as tolerated with HR, blood pressure monitoring, and Borg Perceived Exertion to assess subjective cardiopulmonary exercise tolerance. Treadmill training velocity will advance as tolerated by week 6 to a target intensity of 70-80% maximal HRR. Duration will similarly advance to a target of 30 minutes by week 6. Following week 6, the progressive training protocol will continue with attempts to increase velocity on a weekly basis and increase duration by 5 minutes bi-weekly to peak at 50 minutes. After week 6, the target HR goal will be 75-85% of HRR as tolerated by the subject. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Treadmill Exercise | Six months of treadmill training Treadmill Exercise: Training will be started conservatively with a goal of 15 minutes total duration at 40-50% HRR. Training target HR = %(HRmax - HRrest) + HRrest. Treadmill training velocity will advance as tolerated by week 6 to a target intensity of 70-80% maximal HRR. Duration will similarly advance to a target of 30 minutes by week 6. Following week 6, the progressive training protocol will continue with attempts to increase velocity on a weekly basis and increase duration by 5 minutes bi-weekly to peak at 50 minutes. After week 6, the target HR goal will be 75-85% of HRR as tolerated. |
|
|
| Secondary | The Change in Substrate Oxidation | After a 12 hour fast, economy of hemiparetic gait will be measured using open circuit spirometry during a standard constant load submaximal effort treadmill walking task at a pre-established gait velocity (60% of self-selected floor walking velocity). This slower walking velocity is selected because untrained subjects with stroke usually cannot maintain their self-selected walking pace, precluding steady state measures of oxygen consumption that defines gait economy. We will calculate the change in respiratory exchange ratio from rest to the final 3 minutes of a 10-minute walk under steady state oxygen consumption conditions (RER at 60%VO2peak-RER at rest). Subjects not achieving a plateau in VO2 will be re-tested at a lower velocity on a different date to eliminate potential confounding effects of fatigue on testing. | Posted | Mean | Standard Deviation | ratio change | measured at baseline and following 6 months of treadmill training or stretching (control) |
|
|
|
| Secondary | The Change in Circulating Nitrotyrosine | Plasma will be used to quantitate circulating nitrotyrosine concentrations | Posted | Mean | Standard Deviation | % change | measured at baseline and following 6 months of treadmill training or stretching (control) |
|
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|
| 0 |
| 19 |
| 1 |
| 19 |
| 0 |
| 19 |
| EG001 | Treadmill Exercise | Six months of treadmill training Treadmill Exercise: Training will be started conservatively with a goal of 15 minutes total duration at 40-50% HRR. Training target HR = %(HRmax - HRrest) + HRrest. Treadmill training velocity will advance as tolerated by week 6 to a target intensity of 70-80% maximal HRR. Duration will similarly advance to a target of 30 minutes by week 6. Following week 6, the progressive training protocol will continue with attempts to increase velocity on a weekly basis and increase duration by 5 minutes bi-weekly to peak at 50 minutes. After week 6, the target HR goal will be 75-85% of HRR as tolerated. | 0 | 20 | 1 | 20 | 0 | 20 |
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D001519 | Behavior |