Anterior Cruciate Ligament Reconstruction
Conditions
Brief summary
Traumatic knee injury is common and highly debilitating. Surgical reconstruction/repair improves knee biomechanics and function, but neuromuscular dysfunction persist for years despite rehabilitation, hindering resumption of normal activities, increasing risk of further injury and, in a majority of patients, hastening the development of knee osteoarthritis (OA). Our goal in this research study is to evaluate the utility of neuromuscular electrical stimulation (NMES), initiated following injury and maintained through the early post-surgical period, to prevent muscle atrophy and intrinsic contractile dysfunction compared to active control intervention of micro-electrical stimulation.
Interventions
DEVICENeuromuscular electrical stimulation
Neuromuscular electrical stimulation (NMES) will be performed 5 times/week for one hour each day. NMES will start within 1 week of injury and continue till 3 weeks following surgery.
DEVICEMicrostimulation
Microstimulation will be performed 5 times/week for one hour each day. Microstimulation will start within 1 week of injury and continue till 3 weeks following surgery.
Sponsors
University of Vermont
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* 18-50 yrs * BMI \<35 kg/m2 * acute, first-time, ACL rupture with or without meniscus injury * scheduled to undergo reconstruction with a BPTB autograft
Exclusion criteria
* history of prior knee/lower extremity surgery or non-surgical intervention (eg, intra-articular injection) on either leg * abnormal laxity of any lower extremity ligament other than the injured ACL * signs or symptoms of arthritis, autoimmune or inflammatory disease or diabetes * grade IIIb or greater articular cartilage lesions (ICRS criteria) * women who are/plan on becoming pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cross-sectional Area of Skeletal Muscle Fibers (All Fibers) | Difference between injured and non-injured leg at 3 weeks post-surgery | Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types |
| Maximal Calcium-activated Tension Single Muscle Fiber Tension (Myosin Heavy Chain (MHC) IIA Fibers) | Difference between injured and non-injured leg at 3 weeks post-surgery | Tension (force per unit muscle fiber cross-sectional area) from segments of chemically-skinned single human muscle fibers will be assessed under maximal calcium-activated condition, with muscle fiber type determined post-measurement by gel electrophoresis |
| Maximal Single Muscle Fiber Shortening Velocity (Myosin Heavy Chain (MHC) IIA Fibers) | Difference between injured and non-injured leg at 3 weeks post-surgery | Maximal shortening velocity from segments of chemically-skinned single human muscle fibers will be assessed, with muscle fiber type determined post-measurement by gel electrophoresis |
| Cross-sectional Area of Skeletal Muscle Fibers (Myosin Heavy Chain (MHC) I Fibers) | Difference between injured and non-injured leg at 3 weeks post-surgery | Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types |
| Cross-sectional Area of Skeletal Muscle Fibers (MHC IIA) | Difference between injured and non-injured leg at 3 weeks post-surgery | Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Knee Extensor Peak Isokinetic Torque | Difference between injured and non-injured leg at 6 months post-surgery | Peak isokinetic torque is measures in injured and non-injurd leg at 60 deg/s using dynamometry |
Countries
United States
Participant flow
Recruitment details
Enrollment started in October 2016 and ended in December 2018. Patients were enrolled from an academic orthopedic surgical clinic.
Participants by arm
| Arm | Count |
|---|---|
| NMES Neuromuscular electrical stimulation (NMES) group
Neuromuscular electrical stimulation: Neuromuscular electrical stimulation (NMES) will be performed 5 times/week for one hour each day. NMES will start within 1 week of injury and continue till 3 weeks following surgery. | 14 |
| Microstimulation Microstimulation
Microstimulation: Microstimulation will be performed 5 times/week for one hour each day. Microstimulation will start within 1 week of injury and continue till 3 weeks following surgery. | 11 |
| Total | 25 |
Baseline characteristics
| Characteristic | Microstimulation | Total | NMES |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 25 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 25 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 24 Participants | 14 Participants |
| Region of Enrollment United States | 11 Participants | 25 Participants | 14 Participants |
| Sex: Female, Male Female | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 7 Participants |
| Type of Injury ACL rupture + Cartilage | 3 Participants | 5 Participants | 2 Participants |
| Type of Injury ACL rupture + Meniscus injury | 1 Participants | 4 Participants | 3 Participants |
| Type of Injury ACL rupture + Meniscus injury + Cartilage injury | 1 Participants | 5 Participants | 4 Participants |
| Type of Injury ACL rupture only | 4 Participants | 7 Participants | 3 Participants |
| Type of Injury Exclusion found at surgery (Avulsion) | 1 Participants | 2 Participants | 1 Participants |
| Type of Injury Withdrew prior to surgery | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 14 |
| other Total, other adverse events | 2 / 11 | 2 / 14 |
| serious Total, serious adverse events | 0 / 11 | 0 / 14 |
Outcome results
Primary
Cross-sectional Area of Skeletal Muscle Fibers (All Fibers)
Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types
Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NMES | Cross-sectional Area of Skeletal Muscle Fibers (All Fibers) | Non-injured leg | 2827 micrometer squared | Standard Error 141 |
| NMES | Cross-sectional Area of Skeletal Muscle Fibers (All Fibers) | Injured leg | 2206 micrometer squared | Standard Error 125 |
| Microstimulation | Cross-sectional Area of Skeletal Muscle Fibers (All Fibers) | Non-injured leg | 3318 micrometer squared | Standard Error 153 |
| Microstimulation | Cross-sectional Area of Skeletal Muscle Fibers (All Fibers) | Injured leg | 2376 micrometer squared | Standard Error 130 |
p-value: <0.05ANOVA
Primary
Cross-sectional Area of Skeletal Muscle Fibers (MHC IIA)
Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types
Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NMES | Cross-sectional Area of Skeletal Muscle Fibers (MHC IIA) | Injured leg | 2290 micrometer squared | Standard Error 170 |
| NMES | Cross-sectional Area of Skeletal Muscle Fibers (MHC IIA) | Non-injured leg | 3739 micrometer squared | Standard Error 217 |
| Microstimulation | Cross-sectional Area of Skeletal Muscle Fibers (MHC IIA) | Injured leg | 2206 micrometer squared | Standard Error 167 |
| Microstimulation | Cross-sectional Area of Skeletal Muscle Fibers (MHC IIA) | Non-injured leg | 3318 micrometer squared | Standard Error 204 |
Primary
Cross-sectional Area of Skeletal Muscle Fibers (Myosin Heavy Chain (MHC) I Fibers)
Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types
Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NMES | Cross-sectional Area of Skeletal Muscle Fibers (Myosin Heavy Chain (MHC) I Fibers) | Injured leg | 2552 micrometer squared | Standard Error 134 |
| NMES | Cross-sectional Area of Skeletal Muscle Fibers (Myosin Heavy Chain (MHC) I Fibers) | Non-injured leg | 3217 micrometer squared | Standard Error 151 |
| Microstimulation | Cross-sectional Area of Skeletal Muscle Fibers (Myosin Heavy Chain (MHC) I Fibers) | Injured leg | 2206 micrometer squared | Standard Error 125 |
| Microstimulation | Cross-sectional Area of Skeletal Muscle Fibers (Myosin Heavy Chain (MHC) I Fibers) | Non-injured leg | 2827 micrometer squared | Standard Error 141 |
Primary
Maximal Calcium-activated Tension Single Muscle Fiber Tension (Myosin Heavy Chain (MHC) IIA Fibers)
Tension (force per unit muscle fiber cross-sectional area) from segments of chemically-skinned single human muscle fibers will be assessed under maximal calcium-activated condition, with muscle fiber type determined post-measurement by gel electrophoresis
Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery
Population: Difference in sample size in NMES group is due to the fact that one volunteer did not have sufficient tissue to allow assessment of muscle fiber mechanical properties.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NMES | Maximal Calcium-activated Tension Single Muscle Fiber Tension (Myosin Heavy Chain (MHC) IIA Fibers) | Injured leg | 127 mN/mm2 | Standard Error 7 |
| NMES | Maximal Calcium-activated Tension Single Muscle Fiber Tension (Myosin Heavy Chain (MHC) IIA Fibers) | Non-injured leg | 169 mN/mm2 | Standard Error 7 |
| Microstimulation | Maximal Calcium-activated Tension Single Muscle Fiber Tension (Myosin Heavy Chain (MHC) IIA Fibers) | Injured leg | 137 mN/mm2 | Standard Error 8 |
| Microstimulation | Maximal Calcium-activated Tension Single Muscle Fiber Tension (Myosin Heavy Chain (MHC) IIA Fibers) | Non-injured leg | 175 mN/mm2 | Standard Error 7 |
Primary
Maximal Single Muscle Fiber Shortening Velocity (Myosin Heavy Chain (MHC) IIA Fibers)
Maximal shortening velocity from segments of chemically-skinned single human muscle fibers will be assessed, with muscle fiber type determined post-measurement by gel electrophoresis
Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery
Population: Difference in sample size in NMES group is due to the fact that one volunteer did not have sufficient tissue to allow assessment of muscle fiber mechanical properties.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NMES | Maximal Single Muscle Fiber Shortening Velocity (Myosin Heavy Chain (MHC) IIA Fibers) | Injured leg | 1.74 muscle length per second (ML/s) | Standard Error 0.1 |
| NMES | Maximal Single Muscle Fiber Shortening Velocity (Myosin Heavy Chain (MHC) IIA Fibers) | Non-injured leg | 1.95 muscle length per second (ML/s) | Standard Error 0.09 |
| Microstimulation | Maximal Single Muscle Fiber Shortening Velocity (Myosin Heavy Chain (MHC) IIA Fibers) | Injured leg | 1.67 muscle length per second (ML/s) | Standard Error 0.09 |
| Microstimulation | Maximal Single Muscle Fiber Shortening Velocity (Myosin Heavy Chain (MHC) IIA Fibers) | Non-injured leg | 1.92 muscle length per second (ML/s) | Standard Error 0.09 |
Secondary
Knee Extensor Peak Isokinetic Torque
Peak isokinetic torque is measures in injured and non-injurd leg at 60 deg/s using dynamometry
Time frame: Difference between injured and non-injured leg at 6 months post-surgery
Population: Difference in number of volunteers in analysis is due to loss of patients during 6-month follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NMES | Knee Extensor Peak Isokinetic Torque | 59.4 % (injured to non-injured leg) | Standard Error 7.5 |
| Microstimulation | Knee Extensor Peak Isokinetic Torque | 66.4 % (injured to non-injured leg) | Standard Error 6.5 |
p-value: <0.05t-test, 2 sided