Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty

NCT03051984 | Completed Results FDA Device

• 2 other identifiers: M16-528R01AG050305
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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

Conditions

Knee Osteoarthristis

Outcome Measures

Primary Outcomes (3)

• Cross-sectional Area (CSA) of Muscle Fibers

  CSA of skeletal muscle fibers via myosin heavy chain (MHC) immunohistochemistry

  Baseline and 5-weeks post-TKA surgery

• Intermyofibrillar Mitochondrial Content

  Fractional area of intermyofibrillar (IMF) mitochondria via electron microscopy

  Baseline and 5-weeks post-TKA surgery

• Maximal Calcium-activated Tension Single Muscle Fiber Tension

  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

  Baseline and 5-weeks post-TKA surgery

Secondary Outcomes (5)

• 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

Study Arms (2)

NMES

EXPERIMENTAL

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.

Device: Neuromuscular electrical stimulation

Control

NO INTERVENTION

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

Interventions

Neuromuscular electrical stimulation 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.

Also known as: NMES

NMES

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• symptomatic, primary knee osteoarthritis (OA)
• being considered for total knee arthroplasty

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Vermont: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Vermont College of Medicine

Burlington, Vermont, 05405, United States

Location

Limitations and Caveats

Recruitment for the study was curtailed by the COVID-19 pandemic and its associated research closures.

Results Point of Contact

• Title: Michael Toth
• Organization: University of Vermont College of Medicine

michael.toth@med.uvm.edu

802-656-7989

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: February 7, 2017
• First Posted: February 14, 2017
• Study Start: January 1, 2017
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: October 2, 2025
• Results First Posted: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)