Inflammation and Exercise in Stroke - Full Text View

Purpose

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	Intervention
Stroke Insulin Resistance Sedentary Lifestyle	Behavioral: Aerobic Exercise Behavioral: Stretching

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Aging, Inflammation and Exercise in Chronic Stroke

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Exercise and Physical Fitness

U.S. FDA Resources

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:

TNFalpha (tumor necrosis factor alpha), adiponectin in adipose tissue and skeletal muscle [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
Whole body insulin sensitivity [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
VO2peak (maximal oxygen consumption) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
Muscle insulin signaling proteins [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Circulating cytokines [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
Glucose [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
Insulin areas under the curve by Oral Glucose Tolerance Test [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
Body composition (total body fat, visceral fat, subcutaneous abdominal fat, mid-thigh low density lean tissue) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
Muscle triglyceride content [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
Number of macrophages [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	May 2009
Estimated Study Completion Date:	April 2014
Estimated Primary Completion Date:	April 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Treadmill	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: 2 Stretch	Behavioral: Stretching Stretching, balance exercises, and components of conventional physical therapy-- begins at 15 minutes and progresses to 45 minutes for 6 months

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.

Eligibility

Ages Eligible for Study:	40 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00891514

Contacts

Contact: Jessica Hammers

410-605-7000 ext 4842

jhammers@grecc.umaryland.edu

Locations

United States, Maryland
University of Maryland, VAMC	Recruiting
Baltimore, Maryland, United States, 20705
Contact: Alice S. Ryan, PhD 410-605-7851 aryan@grecc.umaryland.edu
Contact: Jessica Hammers 410-605-7000 ext 4842 jhammers@grecc.umaryland.edu
Principal Investigator: Alice S. Ryan, PhD
Sub-Investigator: Charlene Hafer-Macko, MD

Sponsors and Collaborators

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

More Information

Publications:

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.

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.

Responsible Party:	Alice S. Ryan, PhD, University of Maryland, VA Research Service
ClinicalTrials.gov Identifier:	NCT00891514 History of Changes
Other Study ID Numbers:	AG0118, RO1 AG030075
Study First Received:	April 30, 2009
Last Updated:	September 29, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Institute on Aging (NIA):

Exercise
Inflammation
Insulin Sensitivity

Additional relevant MeSH terms:

Inflammation
Insulin Resistance
Stroke
Cerebral Infarction
Pathologic Processes
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases

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 May 16, 2013