Chronic Muscle Disuse in the Elderly

Osteoarthritis Clinical Trial

Official title:

Muscle Disuse and Contractile Dysfunction in the Elderly

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01190046
• Other study ID #: 033547
• Secondary ID: R01AG033547
• Status: Completed
• Phase: N/A
• First received: August 25, 2010
• Last updated: November 15, 2016
• Start date: October 2010
• Est. completion date: June 2016

Study information

• Verified date: November 2016
• Source: University of Vermont
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to define the effects of chronic disuse on skeletal muscle structure and function in elderly individuals at the cellular and molecular level by examining elderly characterized by chronic muscle disuse (patients with knee osteoarthritis) and healthy elderly no evidence of knee osteoarthritis and normal physical activity levels.

Description:

Skeletal muscle disuse is an important contributing factor to physical disability. Disuse is more frequent in the elderly and they are more susceptible to its debilitating effects because of their diminished physiological reserve. Despite these facts, the mechanisms whereby disuse promotes skeletal muscle contractile dysfunction in this population remain largely undetermined. Therefore, the investigators will systematically test for modifications of single skeletal muscle fiber structure and function that underlie contractile dysfunction. Elderly individuals characterized by chronic muscle disuse (patients with knee osteoarthritis) will be compared to carefully-matched controls with no clinical evidence of knee osteoarthritis and normal activity levels. Thereafter, elderly with chronic disuse will undergo an exercise intervention to remediate muscle disuse. The investigators hypothesize that muscle disuse impairs contractile function, in part, through alterations in myosin kinetics, myofilament protein content and the mechanical properties of the myofilament lattice and that exercise rehabilitation will counteract these deficits. The investigators will specifically examine the effect of disuse on mechanical, kinetic and structural properties and molecular composition of single muscle fibers in cases and controls, as well as determine how increasing muscle use in elderly with chronic disuse via exercise training affects muscle fiber mechanical, kinetic and structural properties and molecular composition. These translational studies will provide the first comprehensive evaluation of the cellular and molecular mechanisms through which muscle disuse alters skeletal muscle structure and contractile function in elderly humans. This knowledge can assist in the development and refinement of preventative and corrective therapies for disability by tailoring these approaches to address specific molecular defects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 60 Years to 80 Years

Eligibility

KNEE OSTEOARTHRITIS PATIENTS

Inclusion Criteria:

• 60-80 yrs of age

• physician-diagnosed, symptomatic knee osteoarthritis

• ambulatory and able to perform lower extremity resistance exercise

Exclusion Criteria:

• rheumatoid arthritis or other autoimmune disease

• chronic heart, lung, kidney or liver disease or hypertension

• diabetes

• history of stroke

• other neurological or musculoskeletal disease

HEALTHY CONTROLS

Criteria are identical to those for knee osteoarthritis patients above, but controls will have no clinical or radiographic evidence of osteoarthritis and will have normal activity physical activity levels.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Osteoarthritis

Intervention

Behavioral:
• Resistance exercise training
Lower extremity resistance exercise training 3x/wk

Locations

Country	Name	City	State
United States	University of Vermont and State Agricultural College	Burlington	Vermont

Sponsors (2)

Lead Sponsor	Collaborator
University of Vermont	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (9)

Callahan DM, Bedrin NG, Subramanian M, Berking J, Ades PA, Toth MJ, Miller MS. Age-related structural alterations in human skeletal muscle fibers and mitochondria are sex specific: relationship to single-fiber function. J Appl Physiol (1985). 2014 Jun 15;116(12):1582-92. doi: 10.1152/japplphysiol.01362.2013. — View Citation

Callahan DM, Miller MS, Sweeny AP, Tourville TW, Slauterbeck JR, Savage PD, Maugan DW, Ades PA, Beynnon BD, Toth MJ. Muscle disuse alters skeletal muscle contractile function at the molecular and cellular levels in older adult humans in a sex-specific man — View Citation

Callahan DM, Tourville TW, Miller MS, Hackett SB, Sharma H, Cruickshank NC, Slauterbeck JR, Savage PD, Ades PA, Maughan DW, Beynnon BD, Toth MJ. Chronic disuse and skeletal muscle structure in older adults: sex-specific differences and relationships to co — View Citation

Callahan DM, Tourville TW, Slauterbeck JR, Ades PA, Stevens-Lapsley J, Beynnon BD, Toth MJ. Reduced rate of knee extensor torque development in older adults with knee osteoarthritis is associated with intrinsic muscle contractile deficits. Exp Gerontol. 2 — View Citation

Gustavson AM, Wolfe P, Falvey JR, Eckhoff DG, Toth MJ, Stevens-Lapsley JE. Men and Women Demonstrate Differences in Early Functional Recovery After Total Knee Arthroplasty. Arch Phys Med Rehabil. 2016 Jul;97(7):1154-62. doi: 10.1016/j.apmr.2016.03.007. — View Citation

Miller MS, Bedrin NG, Ades PA, Palmer BM, Toth MJ. Molecular determinants of force production in human skeletal muscle fibers: effects of myosin isoform expression and cross-sectional area. Am J Physiol Cell Physiol. 2015 Mar 15;308(6):C473-84. doi: 10.1152/ajpcell.00158.2014. — View Citation

Miller MS, Bedrin NG, Callahan DM, Previs MJ, Jennings ME 2nd, Ades PA, Maughan DW, Palmer BM, Toth MJ. Age-related slowing of myosin actin cross-bridge kinetics is sex specific and predicts decrements in whole skeletal muscle performance in humans. J Appl Physiol (1985). 2013 Oct 1;115(7):1004-14. doi: 10.1152/japplphysiol.00563.2013. — View Citation

Miller MS, Callahan DM, Toth MJ. Skeletal muscle myofilament adaptations to aging, disease, and disuse and their effects on whole muscle performance in older adult humans. Front Physiol. 2014 Sep 26;5:369. doi: 10.3389/fphys.2014.00369. Review. — View Citation

Rengo JL, Callahan DM, Savage PD, Ades PA, Toth MJ. Skeletal muscle ultrastructure and function in statin-tolerant individuals. Muscle Nerve. 2016 Feb;53(2):242-51. doi: 10.1002/mus.24722. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Single muscle fiber structure/function		Baseline	No
Primary	Single muscle fiber structure/function		3.5 months (post-training)	No