Trial Outcomes & Findings for Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty (NCT NCT03051984)
NCT ID: NCT03051984
Last Updated: 2025-10-02
Results Overview
CSA of skeletal muscle fibers via myosin heavy chain (MHC) immunohistochemistry
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
23 participants
Primary outcome timeframe
Baseline and 5-weeks post-TKA surgery
Results posted on
2025-10-02
Participant Flow
Recruitment began on January 1, 2017, and ended on January 13, 2022. Volunteers undergoing assessment for TKA were screened from the Adult Reconstruction Service of our Department of Orthopedics and Rehabilitation and local private practices.
Participant milestones
| Measure |
Experimental: NMES
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
12
|
|
Overall Study
COMPLETED
|
10
|
11
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty
Baseline characteristics by cohort
| Measure |
Experimental: NMES
n=11 Participants
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
n=12 Participants
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.2 Years
STANDARD_DEVIATION 7.1 • n=5 Participants
|
64.8 Years
STANDARD_DEVIATION 6.5 • n=7 Participants
|
64.0 Years
STANDARD_DEVIATION 6.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 5-weeks post-TKA surgeryPopulation: Mixed model analysis statistically adjusted for baseline value and sex
CSA of skeletal muscle fibers via myosin heavy chain (MHC) immunohistochemistry
Outcome measures
| Measure |
Experimental: NMES
n=10 Participants
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
n=10 Participants
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
|---|---|---|
|
Cross-sectional Area (CSA) of Muscle Fibers
MHC I fiber cross-sectional area - Baseline
|
2680 micron squared
Standard Error 113
|
2377 micron squared
Standard Error 86
|
|
Cross-sectional Area (CSA) of Muscle Fibers
MHC I fiber cross sectional area - 5-week post-surgery
|
2028 micron squared
Standard Error 83
|
1882 micron squared
Standard Error 68
|
|
Cross-sectional Area (CSA) of Muscle Fibers
MHC IIA fiber cross sectional area - Baseline
|
2039 micron squared
Standard Error 183
|
1971 micron squared
Standard Error 155
|
|
Cross-sectional Area (CSA) of Muscle Fibers
MHC IIA fiber cross sectional area - 5-week post-surgery
|
1623 micron squared
Standard Error 145
|
1389 micron squared
Standard Error 109
|
PRIMARY outcome
Timeframe: Baseline and 5-weeks post-TKA surgeryPopulation: Mixed model analysis adjusting for baseline value and sex
Fractional area of intermyofibrillar (IMF) mitochondria via electron microscopy
Outcome measures
| Measure |
Experimental: NMES
n=10 Participants
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
n=10 Participants
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
|---|---|---|
|
Intermyofibrillar Mitochondrial Content
IMF mitochondria fractional area - Baseline
|
2.36 percent area
Standard Error 0.20
|
2.34 percent area
Standard Error 0.20
|
|
Intermyofibrillar Mitochondrial Content
IMF mitochondria fractional area - 5-week post-surgery
|
2.1 percent area
Standard Error 0.20
|
1.7 percent area
Standard Error 0.20
|
PRIMARY outcome
Timeframe: Baseline and 5-weeks post-TKA surgeryPopulation: Mixed model analysis adjusting for baseline value and sex.
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
Outcome measures
| Measure |
Experimental: NMES
n=8 Participants
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
n=8 Participants
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
|---|---|---|
|
Maximal Calcium-activated Tension Single Muscle Fiber Tension
MHC I tension - Baseline
|
114 milliNewtons per millimiter squared
Standard Error 5
|
111 milliNewtons per millimiter squared
Standard Error 5
|
|
Maximal Calcium-activated Tension Single Muscle Fiber Tension
MHC I tension - 5-week post-surgery
|
112 milliNewtons per millimiter squared
Standard Error 5
|
103 milliNewtons per millimiter squared
Standard Error 5
|
|
Maximal Calcium-activated Tension Single Muscle Fiber Tension
MHC IIA tension - Baseline
|
173 milliNewtons per millimiter squared
Standard Error 5
|
175 milliNewtons per millimiter squared
Standard Error 6
|
|
Maximal Calcium-activated Tension Single Muscle Fiber Tension
MHC IIA tension - 5-week post-surgery
|
132 milliNewtons per millimiter squared
Standard Error 6
|
107 milliNewtons per millimiter squared
Standard Error 8
|
SECONDARY outcome
Timeframe: Baseline and 5-weeks post-TKA surgeryPopulation: Analysis of variance. Note that one patient in the control group did not complete accelerometry assessments.
Physical activity will be assessed by accelerometry.
Outcome measures
| Measure |
Experimental: NMES
n=10 Participants
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
n=10 Participants
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
|---|---|---|
|
Physical Activity Level
Step counts - Baseline
|
4167 steps per day
Standard Error 688
|
4767 steps per day
Standard Error 691
|
|
Physical Activity Level
Step counts - 5-week post-surgery
|
2088 steps per day
Standard Error 588
|
2500 steps per day
Standard Error 587
|
SECONDARY outcome
Timeframe: Baseline and 5-weeks post-TKA surgeryPopulation: Mixed model analysis with control for baseline value and sex
Quadriceps muscle cross-sectional area will be assessed by computed tomography at the mid-thigh on both surgical and non-surgical non-surgical legs.
Outcome measures
| Measure |
Experimental: NMES
n=10 Participants
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
n=11 Participants
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
|---|---|---|
|
Quadriceps Muscle Cross-sectional Area
Surgical Quadriceps cross-sectional area - Baseline
|
45.5 centimeters squared
Standard Error 3.0
|
38.8 centimeters squared
Standard Error 3.1
|
|
Quadriceps Muscle Cross-sectional Area
Surgical Quadriceps cross-sectional area - 5-week post-surgery
|
38.3 centimeters squared
Standard Error 3.3
|
33.8 centimeters squared
Standard Error 2.7
|
|
Quadriceps Muscle Cross-sectional Area
Non-surgical Quadriceps cross-sectional area - Baseline
|
52.0 centimeters squared
Standard Error 3.3
|
46.0 centimeters squared
Standard Error 4.5
|
|
Quadriceps Muscle Cross-sectional Area
Non-surgical Quadriceps cross-sectional area - 5-week post-surgery
|
48.7 centimeters squared
Standard Error 3.6
|
44.9 centimeters squared
Standard Error 3.9
|
SECONDARY outcome
Timeframe: Baseline and 5-weeks post-TKA surgeryPopulation: Analysis of variance.
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 function (more healthy), whereas lower values indicate increasing levels of physical disability/frailty.
Outcome measures
| Measure |
Experimental: NMES
n=10 Participants
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
n=11 Participants
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
|---|---|---|
|
Short Physical Performance Battery
Short Physical Performance - Baseline
|
9.36 Scores on a scale
Standard Error 0.56
|
9.80 Scores on a scale
Standard Error 0.61
|
|
Short Physical Performance Battery
Short Physical Performance Battery - 5-week post-surgery
|
10.45 Scores on a scale
Standard Error 0.53
|
10.10 Scores on a scale
Standard Error 0.55
|
SECONDARY outcome
Timeframe: Baseline and 5-weeks post-TKA surgeryPopulation: Analysis of variance model. Note that n=9 for surgical leg isokinetic peak torque in one NMES volunteer because knee pain prevented completing of strength testing protocol.
Knee extensor isometric peak torque assessed by dynamometry on the surgical leg.
Outcome measures
| Measure |
Experimental: NMES
n=9 Participants
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
n=11 Participants
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
|---|---|---|
|
Knee Extensor Muscle Strength
Surgical Isometric peak torque - Baseline
|
113.0 Newton meter
Standard Error 14.5
|
94.7 Newton meter
Standard Error 9.8
|
|
Knee Extensor Muscle Strength
Surgical Isometric peak torque - 5-week post-surgery
|
65.8 Newton meter
Standard Error 6.9
|
65.7 Newton meter
Standard Error 6.9
|
|
Knee Extensor Muscle Strength
Surgical Isokinetic peak torque - Baseline
|
89.9 Newton meter
Standard Error 9.6
|
58.9 Newton meter
Standard Error 9.6
|
|
Knee Extensor Muscle Strength
Surgical Isokinetic peak torque - 5-week post-surgery
|
53.3 Newton meter
Standard Error 4.2
|
42.5 Newton meter
Standard Error 3.9
|
SECONDARY outcome
Timeframe: Assessed at baseline and 5 weeks post-surgeryPopulation: Analysis of variance model.
Number of repetitions that an individual can complete the sit-to-stand transition in 30 seconds
Outcome measures
| Measure |
Experimental: NMES
n=10 Participants
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
n=11 Participants
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
|---|---|---|
|
30-second Sit-to-stand Test
30-s sit-to-stand - Baseline
|
10.45 repetitions
Standard Error 0.97
|
11.78 repetitions
Standard Error 1.39
|
|
30-second Sit-to-stand Test
30-s sit-to-stand - Post-surgery
|
10.55 repetitions
Standard Error 0.59
|
12.56 repetitions
Standard Error 1.22
|
Adverse Events
Experimental: NMES
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Experimental: Control
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Experimental: NMES
n=10 participants at risk
Volunteers randomized to this arm/group will receive neuromuscular electrical stimulation (NMES) for 5 weeks after total knee arthroplasty (TKA)
|
Experimental: Control
n=11 participants at risk
Patients randomized to this arm/group will not receive any experimental intervention, but will receive standard of care.
|
|---|---|---|
|
General disorders
Low-dose x-ray exposure outside of protocol specified exposure.
|
10.0%
1/10 • Enrollment to end of follow-up, an average of 5 weeks
|
0.00%
0/11 • Enrollment to end of follow-up, an average of 5 weeks
|
|
Musculoskeletal and connective tissue disorders
Excessive bleeding during muscle biopsy procedure.
|
0.00%
0/10 • Enrollment to end of follow-up, an average of 5 weeks
|
9.1%
1/11 • Enrollment to end of follow-up, an average of 5 weeks
|
|
Skin and subcutaneous tissue disorders
Tinea pedis
|
0.00%
0/10 • Enrollment to end of follow-up, an average of 5 weeks
|
9.1%
1/11 • Enrollment to end of follow-up, an average of 5 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place