Strength Training for Skeletal Muscle Adaptation After Stroke

• ClinicalTrials.gov Identifier: NCT00827827
• Recruitment Status: Completed
• First Posted: January 23, 2009
• Results First Posted: January 19, 2015
• Last Update Posted: July 9, 2018
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

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	Not Applicable

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 (Clinical Trial)
• 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: April 1, 2009
• Actual Primary Completion Date: August 31, 2013
• Actual Study Completion Date: June 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) [ Time Frame: Baseline, 3 months ]
2. Change in 1-RM Muscle Strength (Leg Press, Non-Paretic Side) [ Time Frame: Baseline, 3 months ]
3. Change in 1-RM Muscle Strength (Leg Extension, Paretic Side) [ Time Frame: Baseline, 3 Months ]
4. Change in 1-RM Muscle Strength (Leg Extension, Non-Paretic Side) [ Time Frame: Baseline, 3 Months ]
5. Change in Leg Muscle Endurance (Paretic Side) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline, 3 Months ]
8. Change in 10 Meter Walking Speed (Self-Selected) [ Time Frame: Baseline, 3 months ]
9. Change in 10 Meter Walking Speed (Fastest) [ Time Frame: Baseline, 3 Months ]
10. Change in Peak Aerobic Capacity (VO2 Peak) [ Time Frame: Baseline, 3 Months ]
11. Change in Berg Balance Scale [ Time Frame: 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) [ Time Frame: Baseline, 3 months ]
    This and other measures come from Instrumented Walkway (Gait Rite)
13. Change in Paretic Limb Step Time (Fastest) [ Time Frame: Baseline, 3 Months ]
    This and other measures come from Instrumented Walkway (Gait Rite)
14. Change in Non-Paretic Limb Step Time (Self-Selected) [ Time Frame: Baseline, 3 months ]
    This and other measures come from Instrumented Walkway (Gait Rite)
15. Change in Non-Paretic Limb Step Time (Fastest) [ Time Frame: Baseline, 3 Months ]
    This and other measures come from Instrumented Walkway (Gait Rite)
16. Change in Paretic Limb Step Length (Self-Selected) [ Time Frame: Baseline, 3 Months ]
    This and other measures come from Instrumented Walkway (Gait Rite)
17. Change in Paretic Limb Step Length (Fastest) [ Time Frame: Baseline, 3 months ]
    This and other measures come from Instrumented Walkway (Gait Rite)
18. Change in Non-Paretic Limb Step Length (Self-Selected) [ Time Frame: Baseline, 3 Months ]
    This and other measures come from Instrumented Walkway (Gait Rite)
19. Change in Non-Paretic Limb Step Length (Fastest) [ Time Frame: Baseline, 3 Months ]
    This and other measures come from Instrumented Walkway (Gait Rite)

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, Maryland

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

More Information

Publications of Results:

Ivey FM, Prior SJ, Hafer-Macko CE, Katzel LI, Macko RF, Ryan AS. Strength Training for Skeletal Muscle Endurance after Stroke. J Stroke Cerebrovasc Dis. 2017 Apr;26(4):787-794. doi: 10.1016/j.jstrokecerebrovasdis.2016.10.018. Epub 2016 Nov 16.

Ivey FM, Ryan AS. Resistive training improves insulin sensitivity after stroke. J Stroke Cerebrovasc Dis. 2014 Feb;23(2):225-9. doi: 10.1016/j.jstrokecerebrovasdis.2012.12.014. Epub 2013 Jan 22.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT00827827
• Other Study ID Numbers: B6737-R; H30631 ( Other Identifier: Baltimore VAMC )
• First Posted: January 23, 2009
• Results First Posted: January 19, 2015
• Last Update Posted: July 9, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• 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; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases