Clinical trial NCT03051984: Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty
Official title: Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Knee Osteoarthritis
Lead sponsor: University of Vermont
Sponsor class: OTHER
First posted: 2017-02-14
Enrollment: 23
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Cross-sectional area of muscle fibers
timeFrame: Change from baseline cross-sectional area at 5 weeks
measure: Intermyofibrillar mitochondrial content
timeFrame: Change from baseline cross-sectional area at 5 weeks
measure: Maximal calcium-activated tension single muscle fiber tension and shortening velocity
timeFrame: Change from baseline cross-sectional area at 5 weeks
measure: Mitochondrial function
timeFrame: Change from baseline cross-sectional area at 5 weeks
Secondary outcomes:
measure: Physical activity level
timeFrame: Change from baseline cross-sectional area at 5 weeks
measure: Quadriceps muscle cross-sectional area
timeFrame: Change from baseline cross-sectional area at 5 weeks
measure: Physical functional measures
timeFrame: Change from baseline cross-sectional area at 5 weeks
measure: Whole muscle strength
timeFrame: Change from baseline cross-sectional area at 5 weeks
Other outcomes:
Locations:
city: Burlington
country: United States
facility: University of Vermont College of Medicine
state: Vermont
Study officials:
References: