Conditioning Brain Responses to Improve Thigh Muscle Function After Anterior Cruciate Ligament Reconstruction

November 25, 2025 updated by: Chandramouli Krishnan, University of Michigan

Operant Conditioning of Motor Evoked Responses to Improve Quadriceps Function in Individuals With Anterior Cruciate Ligament Reconstruction

The purpose of this study is to examine if thigh muscle weakness and the lack of muscle activation that accompanies ACL injury can be improved through a form of mental coaching and encouragement, known as operant conditioning.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Thigh muscle weakness is a common result after anterior cruciate ligament (ACL) injury and reconstruction surgery. Therefore, reducing thigh muscle weakness after ACL injury and reconstructive surgery is important as the quadriceps muscles act as shock absorbers that protect the knee joint. If significant weakness is present in the quadriceps, the knee is exposed to increased forces and often results in degeneration of the structures in the joint leading to osteoarthritis. Thus, it is important to investigate activation and strength rehabilitation methods for the quadriceps muscles. This research study is being done to learn if thigh muscle weakness and the lack of muscle activation that accompanies ACL injury can be improved by conditioning brain responses (elicited by non-invasive transcranial magnetic stimulation) using a form of training called as operant conditioning.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Chandramouli Krishnan, PhD
  • Phone Number: 734.936.4031
  • Email: mouli@umich.edu

Study Contact Backup

  • Name: Riann Palmieri-Smith, PhD
  • Phone Number: 734-615-3154
  • Email: riannp@umich.edu

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48108
        • University of Michigan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • aged 18-45 years
  • suffered an acute, complete ACL rupture
  • have undergone ACL reconstructive surgery
  • willingness to participate in testing and follow-up as outlined in the protocol

Exclusion Criteria:

  • have suffered a previous ACL injury;
  • have undergone previous major surgery to either knee;
  • have a history of recent significant knee injury (other than ACL) or lower-extremity fracture;
  • have a history of uncontrolled diabetes or hypertension;
  • be pregnant or plan to become pregnant;
  • have metal implants in the head;
  • have electronic devices in their ear or heart (e.g., cochlear implants or cardiac pacemakers);
  • have unexplained recurrent headaches;
  • have a recent history of seizures;
  • be taking drugs that reduce seizure threshold;
  • have a history of repeated fainting spells;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Operant Conditioning
Participants will receive operant conditioning training and single pulse transcranial magnetic stimulation 2-3 times a week for about 8 weeks.
Behavioral: Operant Conditioning
Active encouragement and feedback to increase motor evoked response when stimulated.
Device: Single Pulse Transcranial Magnetic Stimulation
Transcranial magnetic stimulation to elicit a motor evoked response from the quadriceps muscles.
Experimental: Control
Participants will receive single pulse transcranial magnetic stimulation 2-3 times a week for about 8 weeks without operant conditioning training.
Behavioral: Control
Absence of active encouragement and feedback to increase motor evoked response when stimulated.
Device: Single Pulse Transcranial Magnetic Stimulation
Transcranial magnetic stimulation to elicit a motor evoked response from the quadriceps muscles.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in Quadriceps muscle strength
Time Frame: Approximately 8 weeks after the start of intervention
Quadriceps strength will be measured using an isokinetic dynamometer. Improvements in quadriceps strength from baseline to the end of intervention will be assessed and compared between groups.
Approximately 8 weeks after the start of intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes in voluntary activation
Time Frame: Approximately 8 weeks after the start of intervention
Voluntary activation will be measured using an electrical superimposition technique. Improvements in voluntary activation from baseline to the end of intervention will be assessed and compared between groups.
Approximately 8 weeks after the start of intervention

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes in mid-point quadriceps muscle strength
Time Frame: Approximately 4 weeks after the start of intervention (mid-time point evaluation)
Quadriceps strength will be measured using an isokinetic dynamometer. Improvements in quadriceps strength from baseline to the mid-point of intervention will be assessed and compared between groups.
Approximately 4 weeks after the start of intervention (mid-time point evaluation)
Changes in mid-point voluntary activation as measured by percentage activation deficit
Time Frame: Approximately 4 weeks after the start of intervention (mid-time point evaluation)
Voluntary activation will be measured using an electrical superimposition technique. Improvements in voluntary activation from baseline to the mid-point of intervention will be assessed and compared between groups.
Approximately 4 weeks after the start of intervention (mid-time point evaluation)
Changes in motor cortical excitability measures
Time Frame: Approximately after 8 weeks after the start of intervention
Motor cortical excitability will be measured using single- and paired-pulse transcranial magnetic stimulation protocols. Improvements in motor cortical excitability from baseline to the end of intervention will be assessed and compared between groups.
Approximately after 8 weeks after the start of intervention
Changes in Knee Injury and Osteoarthritis Outcome Score
Time Frame: Approximately after 8 weeks after the start of intervention
Knee Injury and Osteoarthritis Outcome Score (KOOS) will be measured using the KOOS questionnaire, which is a self-administered survey of knee function across five domains: pain, symptoms, activities of daily living, sport and recreation function, and knee related quality of life (scores range from 0 to 100, with 0 indicating extreme symptoms and 100 indicating no symptoms). The improvements in KOOS from baseline to the end of intervention will be assessed and compared between groups.
Approximately after 8 weeks after the start of intervention
Changes in International Knee Documentation Committee Score
Time Frame: Approximately after 8 weeks after the start of intervention
International Knee Documentation Committee (IKDC) score will be measured using the IKDC subjective knee evaluation form, which is a survey of self-reported level of knee functioning across different domains (scores range from 0 to 100, with 0 indicating extreme symptoms and 100 indicating no symptoms).The improvements in IKDC score from baseline to the end of intervention will be assessed and compared between groups.
Approximately after 8 weeks after the start of intervention
Changes in Lysholm Knee Score
Time Frame: Approximately after 8 weeks after the start of intervention
Lysholm knee score will be measured using the Lysholm Knee Scoring Scale, which is a questionnaire that assesses knee function after conservatively or surgically treated knee ligament injuries based on activities that require knee movement (scores range from 0 to 100, with 0 indicating extreme symptoms and 100 indicating no symptoms). The improvements in Lysholm score from baseline to the end of intervention will be assessed and compared between groups.
Approximately after 8 weeks after the start of intervention
Changes in Tegner Activity Score
Time Frame: Approximately after 8 weeks after the start of intervention
Tegner activity score will be measured using the Tegner Activity level scale, which is a self-reported measure of activity level (scores range from 0 to 10, with 0 indicating no activity because of knee problems and 10 indicating extremely active in competitive sports). The improvements in Tegner activity score from baseline to the end of intervention will be assessed and compared between groups.
Approximately after 8 weeks after the start of intervention
Changes in Marx Activity Rating Score
Time Frame: Approximately after 8 weeks after the start of intervention
Marx activity rating score will be measured using the Marx Activity Rating Scale, which is a self-reported rating scale designed to measure a subject's level of physical activity in four different categories: running, cutting, deceleration and pivoting (scores range from 0 to 16, with 0 indicating very low activity [< one time in a month] because of knee problems and 16 indicating very high activity [> 4 times in a week] in the four categories). The improvements in Marx activity score from baseline to the end of intervention will be assessed and compared between groups.
Approximately after 8 weeks after the start of intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Michigan

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medical University of South Carolina
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center of Neuromodulation for Rehabilitation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Chandramouli Krishnan, PhD, Assistant Professor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 21, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 24, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 24, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 30, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 3, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 6, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 26, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 25, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HUM00130845
  • P2CHD086844 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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