Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty
Condition: Knee Osteoarthritis
MeSH terms: Muscular Atrophy; Atrophy
Study type: Interventional

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.
    

Intervention name(s): Neuromuscular electrical stimulation
Intervention type(s): Device
Intervention description(s): NMES will be conducted on the quadriceps of the operative leg using a portable stimulation device, starting within 48-72 hrs of surgery. The operative leg will be immobilized at a neutral angle (~30º), with electrodes affixed to the anterior surface of the thigh. Symmetrical, biphasic pulses (400 µs duration at 50 Hz) will be used, with a duty cycle of 25% (10 s on, 30 s off), with patient-selected stimulation intensity to cause visible contractions below pain threshold. NMES sessions will occur 5 d/week, twice daily for 45 min (5 min warm-up) for 5 wks.
Other intervention name(s): NMES
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Other