Trial of Aerobic Exercise Training in Stroke Survivors

• Sponsor: Baltimore VA Medical Center (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00891514
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 98
• Location: 1
• Arms: 2
• Actual Duration (Months): 106.9
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the effects of treadmill training on inflammation in the skeletal muscle and adipose tissue, insulin action in the skeletal muscle, and whole body glucose metabolism in stroke survivors. The fundamental hypothesis of this study is that key inflammatory markers in adipose tissue and skeletal muscle are abnormal, skeletal muscle insulin signaling is impaired, and systemic insulin sensitivity is reduced in hemiparetic stroke patients and that these factors are modifiable and improved by exercise training in stroke patients.

Condition or Disease	Intervention/Treatment	Phase
Stroke; Insulin Resistance; Sedentary Lifestyle	Behavioral: Aerobic Exercise; Behavioral: Stretching	N/A

Detailed Description

Many stroke survivors are sedentary and are at risk for the development of diabetes. We will study the interactions of adipose tissue and the paretic and non-paretic muscle inflammation, insulin signaling and action in hemiparetic stroke patients and the ability to employ exercise training to reverse these abnormalities in this ethnically diverse population. Participants aged 40-75 years with chronic stroke will be randomized to treadmill training versus stretch control group using a one-two-one blocked randomization on race (black vs. white), sex (male vs. female), and glucose tolerance status (normal vs. impaired and type 2 diabetes).

Stroke occurs in over 780,000 persons each year in the U.S., the vast majority reported in persons older than 55 years of age. Following stroke, patients remain at continued high risk for recurrent stroke. Inflammatory processes lead to cardiovascular events/stroke and contribute to disease risk progression by impacting insulin resistance and the development of type 2 diabetes. Interventions that reduce inflammation and improve insulin sensitivity have important clinical implications, especially in the stroke population.

Task-oriented treadmill training is utilized to improve cardiovascular fitness and functional mobility in hemiparetic stroke patients. Additionally, preliminary data indicates that progressive treadmill training in this population improves glucose tolerance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Aging, Inflammation and Exercise in Chronic Stroke
• Actual Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jul 31, 2018
• Actual Study Completion Date: Jul 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aerobic Exercise Treadmill training	Behavioral: Aerobic Exercise; Treadmill training- begins at 15 minutes total duration at 40-50% maximal heart rate reserve 3 times per week, increasing to 60-70% maximal heart rate reserve for 45-60 minutes for 6 months
Active Comparator: Stretch Control Stretching exercises	Behavioral: Stretching; Stretching, balance exercises, and components of conventional physical therapy-- begins at 15 minutes and progresses to 45 minutes for 6 months

Outcome Measures

Primary Outcome Measures

1. VO2peak [Baseline and 6 months]

   maximal oxygen consumption during a treadmill test

Secondary Outcome Measures

1. Whole body insulin sensitivity [Baseline and 6 months]

   glucose utilization during a glucose clamp

2. Cytokines [Baseline and 6 months]

   circulating TNF alpha levels

3. Body fat [Baseline and 6 months]

   whole body percent fat

4. Muscle mass [Baseline and 6 months]

   whole body lean mass

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ischemic or hemorrhagic stroke greater than or equal to 6 months prior with stable residual hemiparetic gait deficits

• Already completed all conventional inpatient and outpatient physical therapy

• Adequate language and neurocognitive function to safely participate in exercise testing and training

• Men or women ages 40-75 years

• Body mass index between 20 to 50 kg/m2

• Non-smoker, or history of no smoking for more than 5 years

• Under the care of a primary care medical provider

Exclusion Criteria:

• Already performing aerobic exercise 3 times a week

• Increased alcohol consumption defined as greater than 2 oz. liquor or 8 oz. of wine or 24 oz. of beer per day

• Cardiac history of:

1. unstable angina

2. recent (less than 3 months prior to study entry) myocardial infarction, congestive heart failure

3. hemodynamically significant valvular dysfunction

• Medical History:

1. recent hospitalization (less than 3 months prior to study entry) for severe medical disease

2. peripheral arterial disease with vascular claudication

3. orthopedic or chronic pain condition restricting exercise

4. pulmonary or renal failure

5. active cancer

6. untreated poorly controlled hypertension measured on at least 2 occasions (greater than 160/100)

7. type I diabetes mellitus, insulin therapy, untreated and/or poorly controlled diabetes with fasting blood glucose of greater than 160

8. smoking within the last 5 years

9. allergy to lidocaine

10. medications: heparin, warfarin, lovenox, beta-blockers, oral steroids

• Neurological history of:

1. dementia with Mini-Mental Status Score less than 23 (less than 17 if education level at or below 8th grade), and diagnostic confirmation by neurologist or psychiatrist

2. severe receptive or global aphasia which confounds testing and training, operationally defined as unable to follow 2 point commands

3. hemiparetic gait from a prior stroke preceding the index stroke defining eligibility (more than one stroke)

4. neurologic disorder restricting exercise, such as Parkinsons Syndrome or myopathy

5. untreated major depression

• Adipose tissue and muscle biopsy exclusion criteria:

1. anti-coagulation therapy with heparin, warfarin, or lovenox (anti-platelet therapy is permitted)

2. bleeding disorder

3. allergy to lidocaine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland, VAMC	Baltimore	Maryland	United States	20705

Sponsors and Collaborators

• Baltimore VA Medical Center
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Alice S. Ryan, PhD, University of Maryland, VA Research Service
• Principal Investigator: Charlene Hafer-Macko, MD, University of Maryland, VA Research Service, Department of Neurology

Study Documents (Full-Text)

None provided.

More Information

Publications

• Hafer-Macko CE, Yu S, Ryan AS, Ivey FM, Macko RF. Elevated tumor necrosis factor-alpha in skeletal muscle after stroke. Stroke. 2005 Sep;36(9):2021-3. Epub 2005 Aug 18.
• Ivey FM, Ryan AS, Hafer-Macko CE, Goldberg AP, Macko RF. Treadmill aerobic training improves glucose tolerance and indices of insulin sensitivity in disabled stroke survivors: a preliminary report. Stroke. 2007 Oct;38(10):2752-8. Epub 2007 Aug 16.
• Ryan AS, Dobrovolny CL, Smith GV, Silver KH, Macko RF. Hemiparetic muscle atrophy and increased intramuscular fat in stroke patients. Arch Phys Med Rehabil. 2002 Dec;83(12):1703-7.

• Responsible Party: Alice S. Ryan, PhD, Professor, Baltimore VA Medical Center
• ClinicalTrials.gov Identifier: NCT00891514
• Other Study ID Numbers: AG0118; R01AG030075
• First Posted: May 1, 2009
• Last Update Posted: Oct 11, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Alice S. Ryan, PhD, Professor, Baltimore VA Medical Center: Exercise; Inflammation; Insulin Sensitivity
• Additional relevant MeSH terms: Stroke; Insulin Resistance

Study Results

No Results Posted as of Oct 11, 2018