Prevention of Skeletal Muscle Adaptations to Traumatic Knee Injury and Surgery

Study Overview
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Brief Summary
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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.

Conditions
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Anterior Cruciate Ligament Reconstruction

Intervention / Treatment
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* Device: Neuromuscular electrical stimulation
* Device: Microstimulation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NMES<br>Neuromuscular electrical stimulation (NMES) group | Device: Neuromuscular electrical stimulation<br>* 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.<br>|
| Active Comparator: Microstimulation<br>Microstimulation | Device: Microstimulation<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Difference between injured and non-injured leg at 3 weeks post-surgery | 
| 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 | Difference between injured and non-injured leg at 3 weeks post-surgery | 
| 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 | Difference between injured and non-injured leg at 3 weeks post-surgery | 
| 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 | Difference between injured and non-injured leg at 3 weeks post-surgery | 
| 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 | Difference between injured and non-injured leg at 3 weeks post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee Extensor Peak Isokinetic Torque | Peak isokinetic torque is measures in injured and non-injurd leg at 60 deg/s using dynamometry | Difference between injured and non-injured leg at 6 months post-surgery |