MiACLR: Michigan Initiative for Anterior Cruciate Ligament Rehabilitation (MiACLR)

This clinical trial evaluates interventions to maximize muscle function and improve cartilage health following anterior cruciate ligament reconstruction. Improving muscle function may improve patient outcomes, improve joint mechanics, and potentially serve as a prevention approach for post-traumatic knee osteoarthritis. Knee osteoarthritis (OA) is a disabling disease that carries a substantial burden to society and to the individual affected.

Study Overview

• Status: Active, not recruiting
• Conditions: Anterior Cruciate Ligament Injury
• Intervention / Treatment: Device: Neuromuscular Electrical Stimulation (NMES); Other: Eccentric Exercise (ECC); Device: Neuromuscular Electrical Stimulation (NMES) placebo; Other: Eccentric Exercise (ECC) placebo

Detailed Description

Restoring quadriceps muscle strength following anterior cruciate ligament reconstruction (ACLR) may help prevent the post-traumatic knee osteoarthritis that affects over 50% of knees 10-20 years after surgical reconstruction. However, a fundamental gap exists in current understanding of how to maximize muscle strength following ACLR, as current rehabilitation fails to restore symmetrical quadriceps strength. The investigators pilot work shows that when patients return to activity, quadriceps strength is ~70% of the uninjured side, which is far below the recommended 90%. Further, these data suggest that embedding high-intensity neuromuscular electrical stimulation (NMES) and eccentric exercise into standard of care ACL rehabilitation leads to higher quadriceps strength when compared with standard of care alone. However, the true efficacy of these interventions is unknown, as controlled trials with adequate sample sizes are currently lacking. The absence of this information serves as the driving force and focus of the proposed trial. Therefore, the investigators propose a double-blind randomized controlled trial where ACLR patients will be randomized to 1 of 2 arms. Study arms will include: 1) 8 weeks of NMES+8 weeks of eccentric exercise; 2) 8 weeks of NMES placebo+8 weeks of eccentric placebo. All study arms will receive standard of care ACL rehabilitation in addition to the study interventions. The investigators hypothesize that subjects receiving NMES+eccentric exercise (Arm 1) will realize greater improvements in strength and biomechanical function at 6 months following ACLR than patients in the placebo study arm. Further, the investigators anticipate that patients in the NMES+eccentric exercise arm (Arm 1) will best eliminate negative changes in cartilage health at 18 months following ACLR. This study is innovative, because it employs interventions that directly target the primary mechanisms that result in strength loss following ACLR and will also evaluate whether improving muscle strength can minimize early changes in cartilage health, which may be indicative of future osteoarthritis. The proposed research is significant because it will identify evidence-based treatment approaches that can successfully counteract the muscle weakness which plagues ACLR patients for years after injury and contributes to the onset of post-traumatic osteoarthritis.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elizabeth Tropiano; Phone Number: 734-615-5373; Email: etropian@umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Ann Arbor, Michigan, United States, 48109
      • MedSport

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acute, complete ACL rupture
• ACL reconstruction with autograft
• Scheduled to undergo ACLR at U of Michigan
• Willingness to participate in testing and follow-up as outlined

Exclusion Criteria:

• Previous surgery to either knee
• Bony fracture accompanying ACL injury
• Patients who experienced a knee dislocation
• Female participants who are pregnant or planning pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NMES+ECC; Neuromuscular electrical stimulation (NMES) and Eccentric Exercise (ECC). Patients randomized to the NMES+ECC group will first receive NMES for 2x/week for 8 weeks, beginning at the first post-operative visit. Beginning at 9 weeks after anterior cruciate ligament reconstruction (ACLR) patients will begin to receive eccentric exercise 2x/week for an additional 8 weeks. For NMES, patients will have electrical stimulation delivered to their quadriceps. Fifteen isometric actions lasting 10 seconds each will be elicited during each session. For eccentric exercise, patients will train for 4 sets of 10 repetitions. This group will also receive standard of care ACL rehabilitation alongside the study interventions.	Device: Neuromuscular Electrical Stimulation (NMES); The electrical stimulator will deliver a 2500 Hz alternating current, modulated at 75 bursts/s, with a ramp-up time of 2-seconds, followed by a 50-second rest period. Stimulus intensity set to generate a maximum voluntary isometric contraction (MVIC) of at least 40& of the contralateral MVIC.; Other Names: Electrical Stimulation; Estim; Other: Eccentric Exercise (ECC); 4 sets of 10 repetitions of an eccentric leg press exercise performed at 70-90% of the 1 repetition maximum
Placebo Comparator: NMES placebo + ECC placebo; Neuromuscular electrical stimulation (NMES) placebo + Eccentric Exercise (ECC)placebo arm. Patients randomized to the NMES placebo + ECC placebo group will first receive NMES placebo for 2x/week for 8 weeks, beginning at the first post-operative physical therapy visit. Beginning at 9 weeks after anterior cruciate ligament reconstruction (ACLR) patients will begin to receive an eccentric exercise placebo 2x/week for 8 weeks. For the NMES placebo, patients will have NMES placebo delivered to their quadriceps 2x/week for 8 weeks beginning at the first post-operative visit. Fifteen isometric actions lasting 10 seconds each will be elicited during each session. For the eccentric exercise placebo, patients will begin to receive eccentric exercise two times per week for 8 weeks. Patients will train for 4 sets of 10 repetitions.	Device: Neuromuscular Electrical Stimulation (NMES) placebo; The electrical stimulator will deliver a 2500 Hz alternating current, modulated at 75 bursts/s, with a ramp-up time of 2-seconds, followed by a 50-second rest period. Stimulus intensity set to generate a maximum voluntary isometric contraction (MVIC) of 10-20% of the contralateral MVIC.; Other: Eccentric Exercise (ECC) placebo; 4 sets of 10 repetitions of an eccentric leg press exercise performed at 10-20% of the 1 repetition maximum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to 6 months isokinetic quadriceps strength index	concentric isokinetic muscle strength at 60 degrees per second	Pre-surgery (baseline), 6 months (6 months post-ACL reconstruction)
Change from baseline to 18 months isokinetic quadriceps strength index	concentric isokinetic muscle strength at 60 degrees per second	Pre-surgery (baseline), 18 months (18 months post-ACL reconstruction)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T1 rho relaxation time symmetry scores for knee joint cartilage	[T1rho value from MRI for right knee (msec)/T1rho value for left knee (msec)] x 100	18 months post-ACL reconstruction
T2 relaxation time symmetry scores for knee joint cartilage	[T2 value from MRI for right knee (msec)/T2 value for left knee (msec)] x 100	18 months post-ACL reconstruction
Knee Flexion Angle at 6 months	Peak knee flexion angle recorded during a single-legged hop (units: degrees)	6 months post-ACL reconstruction
Knee Flexion Angle at 18 months	Peak knee flexion angle recorded during a single-legged hop (units: degrees)	18 months post-ACL reconstruction
Knee Flexion Moment at 6 months	Peak knee flexion moment recorded during a single-legged hop (units: Nm/kg)	6 months post-ACL reconstruction
Knee Flexion Moment at 18 months	Peak knee flexion moment recorded during a single-legged hop (units: Nm/kg)	18 months post-ACL reconstruction

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of North Carolina, Chapel Hill; University of Connecticut; University of Delaware

Publications and helpful links

General Publications

• Rodriguez K, Garcia SA, Spino C, Lepley LK, Pang Y, Wojtys E, Bedi A, Angelini M, Ruffino B, Bolley T, Block C, Kellum J, Swartout A, Palmieri-Smith RM. Michigan Initiative for Anterior Cruciate Ligament Rehabilitation (MiACLR): A Protocol for a Randomized Clinical Trial. Phys Ther. 2020 Dec 7;100(12):2154-2164. doi: 10.1093/ptj/pzaa169.

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2019
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: August 8, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 13, 2018

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Rehabilitation; ACL; Knee; Reconstruction; Electrical Stimulation; Eccentric Exercise
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Knee Injuries; Anterior Cruciate Ligament Injuries
• Other Study ID Numbers: HUM00144992

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No