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Completed

NCT Number: NCT03626857

MiACLR: Michigan Initiative for Anterior Cruciate Ligament Rehabilitation

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.

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Key information

Age range

14 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

MedSport, Ann Arbor, Michigan, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Neuromuscular Electrical Stimulation (NMES)

Device

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

Eccentric Exercise (ECC)

Other

4 sets of 10 repetitions of an eccentric leg press exercise performed at 70-90% of the 1 repetition maximum

Neuromuscular Electrical Stimulation (NMES) placebo

Device

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.

Eccentric Exercise (ECC) placebo

Other

4 sets of 10 repetitions of an eccentric leg press exercise performed at 10-20% of the 1 repetition maximum

Primary outcomes

  1. Immediately Post NMES+ECC Intervention Isokinetic Quadriceps Strength Index

    Time frame: Post-NMES+ECC intervention (approximately 16 weeks post-ACL reconstruction)

    Bilateral concentric isokinetic muscle strength at 60 degrees per second. Limb symmetry index is calculated as (ACL strength/Non-ACL strength)*100

  2. 9 Months Isokinetic Quadriceps Strength Limb Symmetry Index

    Time frame: 9 months (9 months post-ACL reconstruction)

    Bilateral concentric isokinetic muscle strength at 60 degrees per second. Limb symmetry index is calculated as (ACL strength/Non-ACL strength)*100

Secondary outcomes

  1. Knee Flexion Angle at 9 Months

    Time frame: 9 months post-ACL reconstruction

    Peak knee flexion angle of the ACL leg recorded during a single-legged hop (units: degrees)

  2. Knee Flexion Moment at 9 Months

    Time frame: 9 months post-ACL reconstruction

    Peak knee flexion moment recorded during a single-legged hop (units: Nm/kg*m)

  3. Knee Flexion Angle at 18 Months

    Time frame: 18 months post-ACL reconstruction

    Peak knee flexion angle recorded during a single-legged hop (units: degrees)

  4. Knee Flexion Moment at 18 Months

    Time frame: 18 months post-ACL reconstruction

    Peak knee flexion moment recorded during a single-legged hop (units: Nm/kg*m)

  5. T1 Rho Relaxation Time Symmetry Score for Femoral Knee Joint Cartilage

    Time frame: 18 months post-ACL reconstruction

    [T1rho value at the weight bearing region of medial femur from MRI for ACL knee (msec)/T1rho value at the weight bearing region of medial femur for NonACL knee (msec)] x 100

  6. T2 Relaxation Time Symmetry Score for Femoral Knee Joint Cartilage

    Time frame: 18 months post-ACL reconstruction

    [T2 value from MRI at the central weight bearing region of femur for the ACL knee (msec)/T2 value from MRI at the central weight bearing region of femur for the NonACL knee (msec)] x 100

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Collaborators

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

Registry information

Acronym: MiACLR

Important dates

Study start
2019
Primary completion
2025
Study completion
2025
First posted
Aug 13, 2018
Registry last updated
Jan 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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