Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Not specified
- Sponsor
- University of Vermont
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- Cross-sectional Area (CSA) of Muscle Fibers
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
Total knee replacement, or arthroplasty, is the final clinical intervention available to relieve pain and functional limitations related to advanced stage knee osteoarthritis. Despite its beneficial effects, the early post-surgical period is characterized by the erosion of lower extremity muscle size and strength that cause further disability and slow functional recovery. While the detrimental effects of this period on muscle are widely recognized, the mechanisms underlying these adaptations are poorly understood and there are currently no widely-accepted clinical interventions to counter them
Detailed Description
Total knee arthroplasty (TKA) is currently the most common elective surgery in the US and will increase in frequency nearly five-fold by 2030 to 3.5 million surgeries annually. This surgery is most prevalent among older adults with advanced knee osteoarthritis (OA) and its increase is explained primarily by growth in this population. Although TKA reliably reduces joint pain, it fails to correct objectively-measured functional disability due, in part, to dramatic declines in lower-extremity neuromuscular function during the early, postsurgical period. These deficits are never fully remediated, remaining for years after surgery and contributing to persistent disability. Despite these detrimental effects of TKA, the fundamental skeletal muscle adaptations that occur in the early, post-surgical period are poorly defined and understudied and there is currently no widely-accepted, evidence-based intervention to counter these changes. To address this clinical problem, the investigators goals in this application are to define the skeletal muscle structural and functional adaptations following TKA at the whole body, tissue, cellular, organellar and molecular levels in humans in an effort to identify factors contributing to functional disability and to assess the utility of neuromuscular electrical stimulation (NMES) to counter post-surgical muscle adaptations at these same anatomic levels. We hypothesize that TKA fails to remediate physical disability in patients, in part, because of the profound skeletal muscle myofilament and mitochondrial loss and dysfunction that develops during the early, post-surgical period. Moreover, the investigators posit that NMES will improve functional recovery following TKA by countering these early skeletal muscle adaptations. To test this model, the investigators will evaluate participants with knee OA prior to and following TKA for skeletal muscle structure and function at multiple anatomic levels, with patients randomized to receive NMES or sham control intervention during the first 5 weeks post-surgery.
Investigators
Michael J. Toth, Ph.D.
Associate Professor of Medicine
University of Vermont
Eligibility Criteria
Inclusion Criteria
- •symptomatic, primary knee osteoarthritis (OA)
- •being considered for total knee arthroplasty
Exclusion Criteria
- •knee OA secondary to inflammatory/autoimmune disease
- •untreated/uncontrolled hypertension, diabetes or thyroid disease
- •chronic heart failure, actively-treated malignancy, exercise-limiting peripheral vascular disease, stroke or neuromuscular disease
- •body mass index \>38 kg/m2
- •lower extremity blood clot or known coagulopathies
- •implanted pacemaker/ICD
Outcomes
Primary Outcomes
Cross-sectional Area (CSA) of Muscle Fibers
Time Frame: Baseline and 5-weeks post-TKA surgery
CSA of skeletal muscle fibers via myosin heavy chain (MHC) immunohistochemistry
Intermyofibrillar Mitochondrial Content
Time Frame: Baseline and 5-weeks post-TKA surgery
Fractional area of intermyofibrillar (IMF) mitochondria via electron microscopy
Maximal Calcium-activated Tension Single Muscle Fiber Tension
Time Frame: Baseline and 5-weeks post-TKA surgery
Tension (force per unit muscle fiber cross-sectional area) from segments of chemically-skinned single human muscle fibers assessed under maximal calcium-activated condition, with muscle fiber type determined post-measurement by gel electrophoresis
Secondary Outcomes
- Physical Activity Level(Baseline and 5-weeks post-TKA surgery)
- Quadriceps Muscle Cross-sectional Area(Baseline and 5-weeks post-TKA surgery)
- Short Physical Performance Battery(Baseline and 5-weeks post-TKA surgery)
- Knee Extensor Muscle Strength(Baseline and 5-weeks post-TKA surgery)
- 30-second Sit-to-stand Test(Assessed at baseline and 5 weeks post-surgery)