Anterior Cruciate Ligament ReconstructionPhase 1/2NCT02945553

Prevention of Skeletal Muscle Adaptations to Traumatic Knee Injury and Surgery

A Phase 1/2 study testing Neuromuscular electrical stimulation and Microstimulation in people with Anterior Cruciate Ligament Reconstruction, run by University of Vermont at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 50 years
Conditions the study is for: Anterior Cruciate Ligament Reconstruction
What is being tested?: Neuromuscular electrical stimulation and Microstimulation
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 1 siteUnited States
Study dates: Oct 2016to Sep 2019
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Vermont College of Medicine
Burlington, Vermont, 05405

Other trials in United States

About this study

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: Anterior Cruciate Ligament Reconstruction
Being tested: Neuromuscular electrical stimulation, Microstimulation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Neuromuscular electrical stimulationDevice
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.
MicrostimulationDevice
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.

Study groups in NCT02945553
Study group	Role	What they receive
NMES	Experimental	Neuromuscular electrical stimulation (NMES) group Receives: Device: Neuromuscular electrical stimulation
Microstimulation	Active comparator	Microstimulation Receives: Device: Microstimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Difference between injured and non-injured leg at 3 weeks post-surgery

Secondary outcomes (1)

Knee Extensor Peak Isokinetic Torque
Peak isokinetic torque is measures in injured and non-injurd leg at 60 deg/s using dynamometry
Measured: Difference between injured and non-injured leg at 6 months post-surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2016Sep 2019

First posted26 Oct 2016 (estimated)
Study startOct 2016
Primary completionSep 2019
Study completionSep 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Anterior Cruciate Ligament ReconstructionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Investigator, Outcomes assessor
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02945553
Sponsor's protocol ID: M16-609
Status last verified: Nov 2020
First submitted: 24 Oct 2016
Last updated: 5 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: 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.

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.
PubMed 32631074

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Stair Biomechanics and Vibration Study After ACLR
Anterior Cruciate Ligament Reconstruction (ACLR), Anterior Cruciate Ligament Injury
Not yet recruiting
Nerve Block of the Vastus Medialis and Anterior Obturator Branch in Anterior Cruciate Ligament Reconstruction With DIDT Graft
Anterior Cruciate Ligament (ACL) Reconstruction Surgery
Not yet recruiting
Supporting Athletes' Return to Sports After ACL Reconstruction: A Study of a Psychological Readiness Program
Anterior Cruciate Ligament Reconstruction, Anterior Cruciate Ligament Injuries
Recruiting
Interventions to Enhance Quadriceps Output After ACLR
ACL
Recruiting
Graded Exposure and Mindfulness Meditation for Patients Post-ACL Reconstruction
Anterior Cruciate Ligament Injuries

All Anterior Cruciate Ligament Reconstruction trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Prevention of Skeletal Muscle Adaptations to Traumatic Knee Injury and Surgery
ClinicalTrials.gov ID: NCT02945553
Acronym / sponsor ID: M16-609
Conditions: Anterior Cruciate Ligament Reconstruction
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: University of VermontUniversity, hospital or other
Study start: Oct 2016 (actual)
Primary completion: Sep 2019 (actual)
Study completion: Sep 2019 (actual)
First posted: 26 Oct 2016 (estimated)
Results: Posted 5 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
NMES	Experimental	Device: Neuromuscular electrical stimulationNeuromuscular electrical stimulation (NMES) group
Microstimulation	Active comparator	Device: MicrostimulationMicrostimulation

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Neuromuscular electrical stimulationNeuromuscular 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.	Device	NMES
MicrostimulationMicrostimulation 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.	Device	Microstimulation

Primary outcome

Cross-sectional Area of Skeletal Muscle Fibers (All Fibers)
Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery
Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types
Maximal Calcium-activated Tension Single Muscle Fiber Tension (Myosin Heavy Chain (MHC) IIA Fibers)
Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery
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
Maximal Single Muscle Fiber Shortening Velocity (Myosin Heavy Chain (MHC) IIA Fibers)
Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery
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
Cross-sectional Area of Skeletal Muscle Fibers (Myosin Heavy Chain (MHC) I Fibers)
Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery
Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types
Cross-sectional Area of Skeletal Muscle Fibers (MHC IIA)
Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery
Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types

1 secondary outcome

Knee Extensor Peak Isokinetic Torque
Time frame: Difference between injured and non-injured leg at 6 months post-surgery

Results and safety

Results posted to the registry on 5 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
NMES	14	11
Microstimulation	11	9

Primary outcome: Cross-sectional Area of Skeletal Muscle Fibers (All Fibers)

Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery. Mean (Standard Error). Unit: micrometer squared

Measure	NMES n = 11	Microstimulation n = 9
Non-injured leg	2827 (141)	3318 (153)
Injured leg	2206 (125)	2376 (130)

NMES vs Microstimulation: Mean Difference (Final Values): 1596, p <0.05, ANOVA

Primary outcome: Maximal Calcium-activated Tension Single Muscle Fiber Tension (Myosin Heavy Chain (MHC) IIA Fibers)

Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery. Mean (Standard Error). Unit: mN/mm2

Measure	NMES n = 10	Microstimulation n = 9
Injured leg	127 (7)	137 (8)
Non-injured leg	169 (7)	175 (7)

Population analysed: Difference in sample size in NMES group is due to the fact that one volunteer did not have sufficient tissue to allow assessment of muscle fiber mechanical properties.

Primary outcome: Maximal Single Muscle Fiber Shortening Velocity (Myosin Heavy Chain (MHC) IIA Fibers)

Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery. Mean (Standard Error). Unit: muscle length per second (ML/s)

Measure	Microstimulation n = 9	Neuromuscular Electrical Stimlulation n = 10
Injured leg	1.74 (0.1)	1.67 (0.09)
Non-injured leg	1.95 (.09)	1.92 (0.09)

Population analysed: Difference in sample size in NMES group is due to the fact that one volunteer did not have sufficient tissue to allow assessment of muscle fiber mechanical properties.

Primary outcome: Cross-sectional Area of Skeletal Muscle Fibers (Myosin Heavy Chain (MHC) I Fibers)

Time frame: Difference between injured and non-injured leg at 3 weeks post-surgery. Mean (Standard Error). Unit: micrometer squared

Measure	Microstimulation n = 9	Neuromuscular Electrical Stimlulation n = 11
Injured leg	2552 (134)	2206 (125)
Non-injured leg	3217 (151)	2827 (141)

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 6 months post-surgery. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Microstimulation	0 of 11 (0%)	2 of 11 (18.2%)	0 of 11
Neuromuscular Electrical Stimlulation	0 of 14 (0%)	2 of 14 (14.3%)	0 of 14

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32631074Toth 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.
Individual participant dataSharing planned: Yes. 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.

Related trials for Anterior Cruciate Ligament Reconstruction

Not yet recruiting
Stair Biomechanics and Vibration Study After ACLR
Anterior Cruciate Ligament Reconstruction (ACLR), Anterior Cruciate Ligament Injury
Not yet recruiting
Nerve Block of the Vastus Medialis and Anterior Obturator Branch in Anterior Cruciate Ligament Reconstruction With DIDT Graft
Anterior Cruciate Ligament (ACL) Reconstruction Surgery
Not yet recruiting
Supporting Athletes' Return to Sports After ACL Reconstruction: A Study of a Psychological Readiness Program
Anterior Cruciate Ligament Reconstruction, Anterior Cruciate Ligament Injuries
Recruiting
Interventions to Enhance Quadriceps Output After ACLR
ACL
Recruiting
Graded Exposure and Mindfulness Meditation for Patients Post-ACL Reconstruction
Anterior Cruciate Ligament Injuries

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael J. Toth, Ph.D. principal investigator

University of Vermont

Bruce D. Beynnon, Ph.D. principal investigator

University of Vermont

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Neuromuscular electrical stimulation and Microstimulation in people with Anterior Cruciate Ligament Reconstruction, run by University of Vermont at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cross-sectional Area of Skeletal Muscle Fibers (All Fibers) (time frame: Difference between injured and non-injured leg at 3 weeks post-surgery). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02945553, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.