Skeletal Muscle Atrophy and Dysfunction in Human Cancer

Study Overview
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Brief Summary
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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

Official Title
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Skeletal Muscle Atrophy and Dysfunction in Human Cancer

Conditions
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Nonsmall Cell Lung Cancer

Intervention / Treatment
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* Behavioral: Exercise


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise<br>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. | Behavioral: Exercise<br>* Unilateral lower limb resistance exercise will be performed 3 times per week for 8 weeks in non-small cell lung cancer patients on only one leg, while the contralateral leg serves as a non-exercising control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cross-sectional area of skeletal muscle fibers | Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types | Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks | 
| Single muscle fiber contractile function | 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 | Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks | 
| Mitochondrial content | Mitochondrial content will be assessed by electron microscopy. | Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks | 
| Mitochondrial function | Mitochondrial function will be assessed on isolated mitochondria | Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole muscle size | Whole muscle size will be measured by computed tomography at the mid-thigh level. | Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks | 
| Whole muscle isometric function | 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. | Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks | 
| Whole muscle isokinetic function | Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks by isokinetic dynamometry | Difference between the change in the exercised and non-exercised leg from baseline to 8 weeks |