Skeletal Muscle Atrophy and Dysfunction in Human Cancer
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Nonsmall Cell Lung Cancer
- Sponsor
- University of Vermont
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- Mitochondrial function
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
Cancer and its treatment can have profound effects on skeletal muscle, the most well-recognized being atrophy, weakness and diminished oxidative capacity. These adaptations negatively impact quality of life, treatment decisions and survival. Despite these consequences, the factors promoting these adaptations remain poorly defined and understudied in human patients. To address this gap in knowledge, our goal in this study is to examine the role of muscle disuse as a regulator of muscle size and function in human cancer patients
Investigators
Michael J. Toth, Ph.D.
Associate Professor of Medicine
University of Vermont
Eligibility Criteria
Inclusion Criteria
- •50-75 yrs of age
- •histologically-documented, stage III or IV non-small cell lung carcinoma (NSCLC)
- •estimated life expectancy \>6 mos
- •Karnofsky's performance score of ≥70
Exclusion Criteria
- •history, signs or symptoms of inflammatory or autoimmune disease
- •uncontrolled hypertension
- •heart or renal failure
- •exercise limitations from peripheral vascular disease or stroke
- •neuromuscular disease
- •knee/hip replacement
- •additional, actively-treated malignancy or history of malignancy, except non-melanoma skin cancer
- •taking medication that can have anti-coagulant effects that cannot be stopped prior to the muscle biopsy
Outcomes
Primary Outcomes
Mitochondrial function
Time Frame: Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks
Mitochondrial function will be assessed on isolated mitochondria
Cross-sectional area of skeletal muscle fibers
Time Frame: Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks
Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types
Mitochondrial content
Time Frame: Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks
Mitochondrial content will be assessed by electron microscopy.
Single muscle fiber contractile function
Time Frame: Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks
Segments of chemically-skinned single human muscle fibers will be assessed for cellular and molecular contractile parameters under maximal calcium-activated conditions, with muscle fiber type determined post-measurement by gel electrophoresis
Secondary Outcomes
- Whole muscle isokinetic function(Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks)
- Whole muscle isometric function(Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks)
- Whole muscle size(Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks)