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

• ClinicalTrials.gov Identifier: NCT03626857
• Recruitment Status: Recruiting
• First Posted: August 13, 2018
• Last Update Posted: October 26, 2022
• Sponsor: University of Michigan
• 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
• Information provided by (Responsible Party): Riann Palmieri-Smith, University of Michigan

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Anterior Cruciate Ligament Injury	Device: Neuromuscular Electrical Stimulation (NMES); Other: Eccentric Exercise (ECC); Device: Neuromuscular Electrical Stimulation (NMES) placebo; Other: Eccentric Exercise (ECC) placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: MiACLR: Michigan Initiative for Anterior Cruciate Ligament Rehabilitation
• Actual Study Start Date: February 22, 2019
• Estimated Primary Completion Date: September 30, 2024
• Estimated Study Completion Date: September 30, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change from baseline to 6 months isokinetic quadriceps strength index [ Time Frame: Pre-surgery (baseline), 6 months (6 months post-ACL reconstruction) ]
   concentric isokinetic muscle strength at 60 degrees per second
2. Change from baseline to 18 months isokinetic quadriceps strength index [ Time Frame: Pre-surgery (baseline), 18 months (18 months post-ACL reconstruction) ]
   concentric isokinetic muscle strength at 60 degrees per second

Secondary Outcome Measures :

1. T1 rho relaxation time symmetry scores for knee joint cartilage [ Time Frame: 18 months post-ACL reconstruction ]
   [T1rho value from MRI for right knee (msec)/T1rho value for left knee (msec)] x 100
2. T2 relaxation time symmetry scores for knee joint cartilage [ Time Frame: 18 months post-ACL reconstruction ]
   [T2 value from MRI for right knee (msec)/T2 value for left knee (msec)] x 100
3. Knee Flexion Angle at 6 months [ Time Frame: 6 months post-ACL reconstruction ]
   Peak knee flexion angle recorded during a single-legged hop (units: degrees)
4. 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)
5. Knee Flexion Moment at 6 months [ Time Frame: 6 months post-ACL reconstruction ]
   Peak knee flexion moment recorded during a single-legged hop (units: Nm/kg)
6. 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)

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Riann M Palmieri-Smith, PhD; 734-615-3154; riannp@umich.edu

Contact: Elizabeth Tropiano; 734-615-5373; etropian@umich.edu

Locations

United States, Michigan

MedSport; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Riann Palmieri-Smith, PhD 734-615-3154 riannp@umich.edu

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Riann M Palmieri-Smith, PhD 734-615-3154 riannp@umich.edu

Sponsors and Collaborators

University of Michigan

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

University of Connecticut

University of Delaware

University of North Carolina, Chapel Hill

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Riann Palmieri-Smith, Associate Professor, University of Michigan
• ClinicalTrials.gov Identifier: NCT03626857
• Other Study ID Numbers: HUM00144992
• First Posted: August 13, 2018
• Last Update Posted: October 26, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Riann Palmieri-Smith, University of Michigan:

Knee; ACL; Reconstruction; Rehabilitation; Eccentric Exercise; Electrical Stimulation

Additional relevant MeSH terms:

Anterior Cruciate Ligament Injuries; Knee Injuries; Leg Injuries; Wounds and Injuries