Prevention of Skeletal Muscle Adaptations to Traumatic Knee Injury and Surgery

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.

Study Overview

• Status: Completed
• Conditions: Anterior Cruciate Ligament Reconstruction
• Intervention / Treatment: Device: Neuromuscular electrical stimulation; Device: Microstimulation

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NMES; Neuromuscular electrical stimulation (NMES) group	Device: 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.
Active Comparator: Microstimulation	Device: 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Vermont
• Investigators: Principal Investigator: Michael J. Toth, Ph.D., University of Vermont; Principal Investigator: Bruce D. Beynnon, Ph.D., University of Vermont

Publications and helpful links

General Publications

• Toth MJ, Tourville TW, Voigt TB, Choquette RH, Anair BM, Falcone MJ, Failla MJ, Stevens-Lapslaey JE, Endres NK, Slauterbeck JR, Beynnon BD. Utility of Neuromuscular Electrical Stimulation to Preserve Quadriceps Muscle Fiber Size and Contractility After Anterior Cruciate Ligament Injuries and Reconstruction: A Randomized, Sham-Controlled, Blinded Trial. Am J Sports Med. 2020 Aug;48(10):2429-2437. doi: 10.1177/0363546520933622. Epub 2020 Jul 6.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: October 24, 2016
• First Submitted That Met QC Criteria: October 24, 2016
• First Posted (Estimate): October 26, 2016

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: January 1, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: M16-609

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Research data (deidentified) which documents, supports and validates research findings will be stored on the University of Vermont College of Medicine computer system and will be made available upon final acceptance for publication of the major findings from the proposed studies. This includes raw data generated from all clinical and laboratory-based assessments under a data-sharing agreement.