Skeletal Muscle Atrophy and Dysfunction in Human Cancer

Not Applicable

Completed

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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Exercise	Exercise	Lung cancer patients will undergo unilateral resistance exercise 3 times per week for 8 weeks during cancer treatment, while the other leg remains unexercised and will serve as a within-subject control.

Primary Outcome Measures

Name	Time	Method
Mitochondrial function	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	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	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	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 Outcome Measures

Name	Time	Method
Whole muscle isokinetic function	Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks	Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks by isokinetic dynamometry
Whole muscle isometric function	Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks	Whole muscle volitional contractile function will be measured by isometric Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks by isometric dynamometry.
Whole muscle size	Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks	Whole muscle size will be measured by computed tomography at the mid-thigh level.

Locations (1): University of Vermont College of Medicine
🇺🇸
Burlington, Vermont, United States

Receive instant email notifications about changes in this clinical trial

Receive instant email notifications about changes in this clinical trial