NCT03051984

Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty

Completed NA Results posted Last updated 2 October 2025

What this trial tests

NA trial testing Neuromuscular electrical stimulation in Knee Osteoarthristis in 23 participants. Completed in 30 June 2023.

Timeline

1 January 2017

Primary endpoint
30 June 2023

30 June 2023

Quick facts

Lead sponsor	University of Vermont
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	other
Enrollment	23
Start date	1 January 2017
Primary completion	30 June 2023
Estimated completion	30 June 2023
Sites	1 location across United States

Drugs / interventions tested

• Neuromuscular electrical stimulation

Conditions studied

• Knee Osteoarthristis — all drugs for Knee Osteoarthristis →

Sponsor

University of Vermont

Who can join

Adults 50 to 75, any sex, with Knee Osteoarthristis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cross-sectional Area (CSA) of Muscle Fibers Primary · Baseline and 5-weeks post-TKA surgery

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

MHC I fiber cross-sectional area - Baseline

Group	Value	95% CI
Experimental: NMES	2680	± 113
Experimental: Control	2377	± 86

MHC I fiber cross sectional area - 5-week post-surgery

Group	Value	95% CI
Experimental: NMES	2028	± 83
Experimental: Control	1882	± 68

MHC IIA fiber cross sectional area - Baseline

Group	Value	95% CI
Experimental: NMES	2039	± 183
Experimental: Control	1971	± 155

MHC IIA fiber cross sectional area - 5-week post-surgery

Group	Value	95% CI
Experimental: NMES	1623	± 145
Experimental: Control	1389	± 109

Intermyofibrillar Mitochondrial Content Primary · Baseline and 5-weeks post-TKA surgery

Fractional area of intermyofibrillar (IMF) mitochondria via electron microscopy

IMF mitochondria fractional area - Baseline

Group	Value	95% CI
NMES	2.36	± 0.20
Control	2.34	± 0.20

IMF mitochondria fractional area - 5-week post-surgery

Group	Value	95% CI
NMES	2.1	± 0.20
Control	1.7	± 0.20

Maximal Calcium-activated Tension Single Muscle Fiber Tension Primary · 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

MHC I tension - Baseline

Group	Value	95% CI
Experimental: NMES	114	± 5
Experimental: Control	111	± 5

MHC I tension - 5-week post-surgery

Group	Value	95% CI
Experimental: NMES	112	± 5
Experimental: Control	103	± 5

MHC IIA tension - Baseline

Group	Value	95% CI
Experimental: NMES	173	± 5
Experimental: Control	175	± 6

MHC IIA tension - 5-week post-surgery

Group	Value	95% CI
Experimental: NMES	132	± 6
Experimental: Control	107	± 8

Physical Activity Level Secondary · Baseline and 5-weeks post-TKA surgery

Physical activity will be assessed by accelerometry.

Step counts - Baseline

Group	Value	95% CI
Experimental: NMES	4167	± 688
Experimental: Control	4767	± 691

Step counts - 5-week post-surgery

Group	Value	95% CI
Experimental: NMES	2088	± 588
Experimental: Control	2500	± 587

Quadriceps Muscle Cross-sectional Area Secondary · Baseline and 5-weeks post-TKA surgery

Quadriceps muscle cross-sectional area will be assessed by computed tomography at the mid-thigh on both surgical and non-surgical non-surgical legs.

Surgical Quadriceps cross-sectional area - Baseline

Group	Value	95% CI
Experimental: NMES	45.5	± 3.0
Experimental: Control	38.8	± 3.1

Surgical Quadriceps cross-sectional area - 5-week post-surgery

Group	Value	95% CI
Experimental: NMES	38.3	± 3.3
Experimental: Control	33.8	± 2.7

Non-surgical Quadriceps cross-sectional area - Baseline

Group	Value	95% CI
Experimental: NMES	52.0	± 3.3
Experimental: Control	46.0	± 4.5

Non-surgical Quadriceps cross-sectional area - 5-week post-surgery

Group	Value	95% CI
Experimental: NMES	48.7	± 3.6
Experimental: Control	44.9	± 3.9

Short Physical Performance Battery Secondary · Baseline and 5-weeks post-TKA surgery

Physical functional assessment based on 2 lower extremity activities (5-time sit-to-stand, 4-m gait speed) and standing balance (side-side, tandem, semi-tandem) based on time or repetitions (0-4 score) with a minimum score of 0 and a maximal score of 12. Each activity is scored from 0 to 4 based on the level of performance (with higher values indicating better physical function and lower values indicating increasing levels of disability). The scores from the 3 activities are summed to give the total score, which is what is reported. Higher total score values indicate higher levels of physical

Short Physical Performance - Baseline

Group	Value	95% CI
Experimental: NMES	9.36	± 0.56
Experimental: Control	9.80	± 0.61

Short Physical Performance Battery - 5-week post-surgery

Group	Value	95% CI
Experimental: NMES	10.45	± 0.53
Experimental: Control	10.10	± 0.55

Knee Extensor Muscle Strength Secondary · Baseline and 5-weeks post-TKA surgery

Knee extensor isometric peak torque assessed by dynamometry on the surgical leg.

Surgical Isometric peak torque - Baseline

Group	Value	95% CI
Experimental: NMES	113.0	± 14.5
Experimental: Control	94.7	± 9.8

Surgical Isometric peak torque - 5-week post-surgery

Group	Value	95% CI
Experimental: NMES	65.8	± 6.9
Experimental: Control	65.7	± 6.9

Surgical Isokinetic peak torque - Baseline

Group	Value	95% CI
Experimental: NMES	89.9	± 9.6
Experimental: Control	58.9	± 9.6

Surgical Isokinetic peak torque - 5-week post-surgery

Group	Value	95% CI
Experimental: NMES	53.3	± 4.2
Experimental: Control	42.5	± 3.9

30-second Sit-to-stand Test Secondary · Assessed at baseline and 5 weeks post-surgery

Number of repetitions that an individual can complete the sit-to-stand transition in 30 seconds

30-s sit-to-stand - Baseline

Group	Value	95% CI
Experimental: NMES	10.45	± 0.97
Experimental: Control	11.78	± 1.39

30-s sit-to-stand - Post-surgery

Group	Value	95% CI
Experimental: NMES	10.55	± 0.59
Experimental: Control	12.56	± 1.22

Adverse events — posted to ClinicalTrials.gov

Time frame: Enrollment to end of follow-up, an average of 5 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Experimental: NMES

Serious: 0/10 (0%)

Deaths: 0/10

Experimental: Control

Serious: 0/11 (0%)

Deaths: 0/11

Other adverse events (3 terms — click to expand)

Reaction	System	Experimental: NMES	Experimental: Control
Low-dose x-ray exposure outside of protocol specified exposure.	General disorders	—	—
Excessive bleeding during muscle biopsy procedure.	Musculoskeletal and connective tissue disorders	—	—
Tinea pedis	Skin and subcutaneous tissue disorders	—	—

Data from ClinicalTrials.gov NCT03051984 adverse events section.

Sponsor's own description

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

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Sustaining neuromuscular activation after total knee arthroplasty preserves skeletal muscle fiber size, contractility, and innervation in older adults.
   Toth MJ, Savage PD, Snoke DB, Bellefleur ER, et al · · 2025 · PMID 40653208 · DOI 10.1016/j.exger.2025.112831