Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty

NCT ID: NCT03051984

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-01
• Study Completion Date: 2023-06-30

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.

Conditions

Knee Osteoarthristis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

NMES

Neuromuscular electrical stimulation (NMES) will be administered for 5 weeks post-TKA in the quadriceps of the surgical leg. Treatment will occur 5 days per week, twice daily for 45 minutes on each occasion.

Group Type: EXPERIMENTAL

Neuromuscular electrical stimulation

Intervention Type: DEVICE

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.

Control

No intervention will be administered during the 5 weeks post-TKA in the surgical leg.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Neuromuscular electrical stimulation

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.

Intervention Type: DEVICE

Other Intervention Names

NMES

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Vermont

OTHER

Sponsor Role: lead

Responsible Party

Michael J. Toth, Ph.D.

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Vermont College of Medicine

Burlington, Vermont, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

R01AG050305

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M16-528

Identifier Type: -

Identifier Source: org_study_id