Strength Training for Skeletal Muscle Adaptation After Stroke

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00827827
First received: January 22, 2009
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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 our 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 Intervention
Stroke
Other: Exercise- Strength Training
Other: Exercise- Stretching Control

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Strength Training for Skeletal Muscle Adaptation After Stroke

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Bilateral Thigh Muscle Area and Volume by CT scan [ Time Frame: baseline and 3 months (post intervention) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bilateral Thigh Intramuscular Fat by CT [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Histochemical analyses of fiber type and capillary density from Bilateral Thigh Muscle Biopsy samples [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Muscle Fiber proportion and mean cross sectional area by immunohistochemistry [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Myosin Heavy Chain Isoform expression by gel electrophoresis [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Skeletal Muscle TNF-alpha transcript expression by RT-PCR [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Muscle Inflammatory Infiltrates by Immunohistochemistry [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Oral Glucose tolerance Test [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Insulin Sensitivity by Hyperglycemic Clamp Test [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Bilateral Single Limb Strength Testing (Leg Extension and Leg Press) [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Timed Walks (10 meter and 6 minute walk tests [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Balance Testing using Berg Balance Scale [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Peak Fitness by graded treadmill VO2 peak testing [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Bilateral Single Limb Muscle Endurance (Static and Dynamic) [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  • Cognitive Function [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: April 2009
Estimated Study Completion Date: December 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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. We 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 we will screen and consent chronic stroke patients with residual gait deficits. Phase 2 (3 weeks) will consist of baseline testing that includes 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.

  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
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
    • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00827827

Locations
United States, Maryland
VA Maryland Health Care System, Baltimore
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
Investigators
Principal Investigator: Fred Ivey, PhD VA Maryland Health Care System, Baltimore
  More Information

Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00827827     History of Changes
Other Study ID Numbers: B6737-R, H30631
Study First Received: January 22, 2009
Last Updated: May 13, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Stroke
Exercise
Strength Training
Skeletal Muscle
Insulin Sensitivity

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia

ClinicalTrials.gov processed this record on September 11, 2014