Strength Training for Skeletal Muscle Adaptation After Stroke

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00827827
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 2
• Actual Duration (Months): 110.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Chronically disabled stroke survivors experience accelerated skeletal muscle atrophy and other detrimental changes to muscle and surrounding tissues on the paretic side. This unilateral tissue-level damage contributes to worsening disability and insulin resistance. This VA Merit Award will advance the investigators' understanding of the potential for strength training (ST) to reverse stroke-related muscle abnormalities to improve metabolic health, strength, and function. It will be the first study to thoroughly investigate the effects of ST on muscle atrophy, intramuscular fat, muscle fiber characteristics, capillary density and insulin sensitivity after stroke.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Other: Exercise- Strength Training; Other: Exercise- Stretching Control	N/A

Detailed Description

This study investigates the hypothesis that a novel, high intensity, high repetition ST program will improve abnormalities in paretic and non-paretic leg muscle volume and composition compared to an attention-matched control regimen of supervised stretching over a 3-month intervention period in those disabled by stroke. The investigators further hypothesize that ST-induced skeletal muscle adaptation will translate into improved insulin sensitivity, strength, and function in this population. The specific objectives are to: 1) Determine the effects ST compared to a control intervention on paretic and non-paretic abnormalities in skeletal muscle volume, intramuscular fat, muscle fiber distribution, muscle capillary density, and muscle inflammation in chronically disabled stroke survivors. 2) Determine the effects ST compared to a control intervention on insulin sensitivity in stroke survivors, and whether structural and cellular skeletal muscle mechanisms contribute to improvements in insulin sensitivity after ST. 3) Determine the effects ST compared to a control intervention on physical function (strength, walking speed and balance) in stroke survivors, and whether structural skeletal muscle mechanisms predict ST-induced functional improvement.

The project design consists of 4 phases over 5 months for stroke participants enrolled in either of the two intervention arms (ST vs. CONTROL). During phase 1 the investigators will screen and consent chronic stroke patients with residual gait deficits. Phase 2 (3 weeks) will consist of baseline testing that includes dual energy X-ray absorptiometry (DEXA) scanning, bilateral CT scanning of the legs, bilateral vastus lateralis muscle biopsies, strength testing, timed walks, balance measurements, oral glucose tolerance testing, and hyperglycemic clamp testing. Following completion of baseline testing, volunteers are to be randomized to ST or the CONTROL group. Phase 3 (Intervention Phase, 3 months) will begin with 2 sessions of acclimatization for those assigned to the ST group. ST will then be progressed to 2 sets of 20 repetitions on each leg on each machine (Keiser Leg Press, Leg Extension, Leg Curl) with gradual increases in resistance over 3 months. Those in the CONTROL group will receive equal exposure to health care personnel in the Baltimore VA Exercise facility, performing a full battery of upper and lower body passive and active stretching exercises at each intervention session. In Phase 4 all baseline testing and laboratory analyses will be repeated.

Developing evidence-based therapies to combat skeletal muscle deterioration is highly relevant for chronically disabled stoke survivors. There is mounting evidence that current models of post-stroke rehabilitation are not optimal for maximizing recovery of muscle mass, strength, and metabolic health. The proposed research will develop new insight into the utility of progressive ST for reversing detrimental changes to gross muscle composition, muscle molecular phenotype, muscle inflammation, and muscle capillarization. Changes to any or all of these muscle parameters should have measurable impact on both whole body insulin sensitivity and function. Collectively, the results from this trial may change the current standard of care for stroke survivors by providing evidenced reasons for augmenting physical therapists' treatments, allowing more intense and diverse therapy sessions for maintenance of skeletal muscle.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Strength Training for Skeletal Muscle Adaptation After Stroke
• Actual Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Aug 31, 2013
• Actual Study Completion Date: Jun 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors.	Other: Exercise- Strength Training; 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.
Active Comparator: Arm 2 Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables.	Other: Exercise- Stretching Control; 3x per week upper and lower body stretching mixed with active and passive range of motion exercises

Outcome Measures

Primary Outcome Measures

1. Change in 1-repetition Maximum (RM) Muscle Strength (Leg Press, Paretic Side) [Baseline, 3 months]

2. Change in 1-RM Muscle Strength (Leg Press, Non-Paretic Side) [Baseline, 3 months]

3. Change in 1-RM Muscle Strength (Leg Extension, Paretic Side) [Baseline, 3 Months]

4. Change in 1-RM Muscle Strength (Leg Extension, Non-Paretic Side) [Baseline, 3 Months]

5. Change in Leg Muscle Endurance (Paretic Side) [Baseline, 3 Months]

   Tests how training impacts the total number of submaximal repetitions a participant can perform according to standardized cadence (at the same absolute level of resistance, pre and post).

6. Change in Leg Muscle Endurance (Non-Paretic Side) [Baseline, 3 months]

   Tests how training impacts the total number of submaximal repetitions a participant can perform according to standardized cadence (at the same absolute level of resistance, pre and post).

7. Change in 6-minute Walk Distance [Baseline, 3 Months]

8. Change in 10 Meter Walking Speed (Self-Selected) [Baseline, 3 months]

9. Change in 10 Meter Walking Speed (Fastest) [Baseline, 3 Months]

10. Change in Peak Aerobic Capacity (VO2 Peak) [Baseline, 3 Months]

11. Change in Berg Balance Scale [Baseline, 3 months]

    This measure is a 14 item scale, with each item scored (0-4) and summed for a maximum score of 56 points. Range is 0-56 and higher values represent a better outcome.

12. Change in Paretic Limb Step Time (Self-Selected) [Baseline, 3 months]

    This and other measures come from Instrumented Walkway (Gait Rite)

13. Change in Paretic Limb Step Time (Fastest) [Baseline, 3 Months]

    This and other measures come from Instrumented Walkway (Gait Rite)

14. Change in Non-Paretic Limb Step Time (Self-Selected) [Baseline, 3 months]

    This and other measures come from Instrumented Walkway (Gait Rite)

15. Change in Non-Paretic Limb Step Time (Fastest) [Baseline, 3 Months]

    This and other measures come from Instrumented Walkway (Gait Rite)

16. Change in Paretic Limb Step Length (Self-Selected) [Baseline, 3 Months]

    This and other measures come from Instrumented Walkway (Gait Rite)

17. Change in Paretic Limb Step Length (Fastest) [Baseline, 3 months]

    This and other measures come from Instrumented Walkway (Gait Rite)

18. Change in Non-Paretic Limb Step Length (Self-Selected) [Baseline, 3 Months]

    This and other measures come from Instrumented Walkway (Gait Rite)

19. Change in Non-Paretic Limb Step Length (Fastest) [Baseline, 3 Months]

    This and other measures come from Instrumented Walkway (Gait Rite)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Stroke greater than 6 months prior with residual hemiparetic gait in women or men aged 40-85 years

• Completion of all regular post-stroke physical therapy

• Adequate language and neurocognitive function to participate in testing and training and to give adequate informed consent

Exclusion Criteria:

• Alcohol consumption greater than 3 oz. liquor, or 3 x 4 oz glasses of wine, or 3 x 12 oz. beers per day, by self-report

• clinical history of:

• unstable angina

• recent (less than 3 months) myocardial infarction or congestive heart failure (NYHA category II)

• hemodynamically significant valvular dysfunction

• peripheral arterial occlusive disease (PAOD) with claudication

• major orthopedic, chronic pain, or non-stroke neuromuscular disorders restricting exercise

• pulmonary or renal failure

• poorly controlled hypertension (greater than 190/110)

• recent hospitalization for severe disease or surgery

• severe or global receptive aphasia which confounds reliable testing and training

• Allergy to lidocaine

• Known muscle disorder

• Taking Coumadin or Lovenox (contraindication for muscle biopsies)

• Dementia

• Untreated major depression

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: Frederick M Ivey, PhD, Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT00827827
• Other Study ID Numbers: B6737-R; H30631
• First Posted: Jan 23, 2009
• Last Update Posted: Jul 9, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: Stroke; Exercise; Strength Training; Skeletal Muscle; Insulin Sensitivity
• Additional relevant MeSH terms: Stroke

Study Results

Participant Flow

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Period Title: Overall Study
STARTED	22	16
COMPLETED	14	16
NOT COMPLETED	8	0

Baseline Characteristics

Arm/Group Title	Strength Training	Stretching Control	Total
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises	Total of all reporting groups
Overall Participants	22	16	38
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 86.4%	14 87.5%	33 86.8%
>=65 years	3 13.6%	2 12.5%	5 13.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.9 (11.5)	55.2 (8.7)	56.2 (10.3)
Sex: Female, Male (Count of Participants)
Female	6 27.3%	4 25%	10 26.3%
Male	16 72.7%	12 75%	28 73.7%
Region of Enrollment (participants) [Number]
United States	22 100%	16 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	Change in 1-repetition Maximum (RM) Muscle Strength (Leg Press, Paretic Side)
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

All participants for whom strength measurements were recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	14	16
Mean (Standard Error) [lbs]	126.1 (22.2)	11.3 (14.6)

2. Primary Outcome

Title	Change in 1-RM Muscle Strength (Leg Press, Non-Paretic Side)
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

All participants for whom strength measurements were recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	14	16
Mean (Standard Error) [lbs]	93.2 (26.1)	22.7 (16.4)

3. Primary Outcome

Title	Change in 1-RM Muscle Strength (Leg Extension, Paretic Side)
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom strength measurements were recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	14	16
Mean (Standard Error) [lbs]	28.6 (4.3)	3.4 (2.4)

4. Primary Outcome

Title	Change in 1-RM Muscle Strength (Leg Extension, Non-Paretic Side)
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom strength measurements were recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	16
Mean (Standard Error) [lbs]	20.8 (0.4)	0.4 (2.6)

5. Primary Outcome

Title	Change in Leg Muscle Endurance (Paretic Side)
Description	Tests how training impacts the total number of submaximal repetitions a participant can perform according to standardized cadence (at the same absolute level of resistance, pre and post).
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom muscle endurance measurements were recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	14	15
Mean (Standard Error) [repetitions]	27.4 (4.5)	2.0 (2.1)

6. Primary Outcome

Title	Change in Leg Muscle Endurance (Non-Paretic Side)
Description	Tests how training impacts the total number of submaximal repetitions a participant can perform according to standardized cadence (at the same absolute level of resistance, pre and post).
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

All participants for whom muscle endurance measurements were recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	14	15
Mean (Standard Error) [repetitions]	27.5 (5.0)	1.8 (1.8)

7. Primary Outcome

Title	Change in 6-minute Walk Distance
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom 6-minute walk distance was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Controls
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	16
Mean (Standard Error) [feet]	132.3 (48.3)	-2.1 (21.6)

8. Primary Outcome

Title	Change in 10 Meter Walking Speed (Self-Selected)
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

All participants for whom 10 Meter walking Speed (Self-Selected) was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Controls
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	14	16
Mean (Standard Error) [meters/ second]	0.16 (0.09)	0.03 (0.06)

9. Primary Outcome

Title	Change in 10 Meter Walking Speed (Fastest)
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom 10 Meter walking Speed (Fastest-Safe) was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Controls
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	14
Mean (Standard Error) [meters/ second]	0.24 (0.10)	0.09 (0.08)

10. Primary Outcome

Title	Change in Peak Aerobic Capacity (VO2 Peak)
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom Peak Aerobic Capacity was recorded during Graded Treadmill Test at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Controls
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	14	15
Mean (Standard Error) [mls/kg/min]	1.2 (0.6)	-0.4 (0.5)

11. Primary Outcome

Title	Change in Berg Balance Scale
Description	This measure is a 14 item scale, with each item scored (0-4) and summed for a maximum score of 56 points. Range is 0-56 and higher values represent a better outcome.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

All participants for whom a Berg Score was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	14	16
Mean (Standard Error) [Scores on a scale]	0.3 (0.6)	-0.1 (0.5)

12. Primary Outcome

Title	Change in Paretic Limb Step Time (Self-Selected)
Description	This and other measures come from Instrumented Walkway (Gait Rite)
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

All participants for whom measurement was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	11
Mean (Standard Error) [seconds]	-0.04 (0.03)	-0.03 (0.03)

13. Primary Outcome

Title	Change in Paretic Limb Step Time (Fastest)
Description	This and other measures come from Instrumented Walkway (Gait Rite)
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom measurement was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	10
Mean (Standard Error) [seconds]	0.00 (0.03)	0.00 (0.02)

14. Primary Outcome

Title	Change in Non-Paretic Limb Step Time (Self-Selected)
Description	This and other measures come from Instrumented Walkway (Gait Rite)
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

All participants for whom measurement was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	11
Mean (Standard Error) [seconds]	-0.01 (0.02)	-0.07 (0.05)

15. Primary Outcome

Title	Change in Non-Paretic Limb Step Time (Fastest)
Description	This and other measures come from Instrumented Walkway (Gait Rite)
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom measurement was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	10
Mean (Standard Error) [seconds]	-0.01 (0.02)	-0.01 (0.01)

16. Primary Outcome

Title	Change in Paretic Limb Step Length (Self-Selected)
Description	This and other measures come from Instrumented Walkway (Gait Rite)
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom measurement was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	11
Mean (Standard Error) [cm]	4.0 (1.5)	1.1 (2.8)

17. Primary Outcome

Title	Change in Paretic Limb Step Length (Fastest)
Description	This and other measures come from Instrumented Walkway (Gait Rite)
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

All participants for whom measurement was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	10
Mean (Standard Error) [cm]	3.8 (2.1)	0.9 (2.7)

18. Primary Outcome

Title	Change in Non-Paretic Limb Step Length (Self-Selected)
Description	This and other measures come from Instrumented Walkway (Gait Rite)
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom measurement was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	11
Mean (Standard Error) [cm]	3.8 (1.4)	0.3 (2.1)

19. Primary Outcome

Title	Change in Non-Paretic Limb Step Length (Fastest)
Description	This and other measures come from Instrumented Walkway (Gait Rite)
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

All participants for whom measurement was recorded at Baseline and 3 months

Arm/Group Title	Strength Training	Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.	Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Measure Participants	13	10
Mean (Standard Error) [cm]	4.6 (1.9)	-0.4 (3.0)

Adverse Events

Arm/Group Title	Strength Training		Stretching Control
Arm/Group Description	Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors. Exercise- Strength Training: 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.		Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables. Exercise- Stretching Control: 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
All Cause Mortality
	Strength Training		Stretching Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Strength Training		Stretching Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/22 (9.1%)		2/16 (12.5%)
General disorders
fell at home	1/22 (4.5%)	1	1/16 (6.3%)	1
hypotensive episode	1/22 (4.5%)	1	0/16 (0%)	0
choked on a pill at home	0/22 (0%)	0	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Strength Training		Stretching Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/22 (13.6%)		9/16 (56.3%)
General disorders
hypotensive event	1/22 (4.5%)	1	2/16 (12.5%)	2
falls outside of training/ testing sessions	0/22 (0%)	0	5/16 (31.3%)	5
muscle strain	1/22 (4.5%)	1	1/16 (6.3%)	1
gout flare-up	0/22 (0%)	0	1/16 (6.3%)	1
adverse reaction to lidocaine during muscle biopsy	1/22 (4.5%)	1	0/16 (0%)	0

Limitations/Caveats

Scanning results and muscle biopsy outcomes are still pending and won't be available for some time. Numbers of participants qualifying for and agreeing to metabolic testing will be too low to yield reportable results.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.