Skeletal Muscle Atrophy and Dysfunction in Human Cancer

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

Study Overview

• Status: Completed
• Conditions: Nonsmall Cell Lung Cancer
• Intervention / Treatment: Behavioral: Exercise

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Behavioral: Exercise; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Vermont
• Collaborators: University of South Carolina
• Investigators: Principal Investigator: Michael J. Toth, Ph.D., University of Vermont

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: October 25, 2016
• First Submitted That Met QC Criteria: October 26, 2016
• First Posted (Estimated): October 31, 2016

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Neurologic Manifestations; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Muscular Atrophy; Atrophy
• Other Study ID Numbers: 16-506

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Research data (deidentified) which documents, supports and validates research findings will be stored on the University of Vermont College of Medicine computer system and will be made available upon final acceptance for publication of the major findings from the proposed studies. This includes raw data generated from all clinical and laboratory-based assessments under a data-sharing agreement.