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fMRIACL-fMRI-TNMTNCT07097077

Study of Functional Magnetic Resonance Signal Variations in Patients Undergoing Anterior Cruciate Ligament Reconstruction With the Application of a Dedicated Neuromotor Training

A study testing Effect of targeted neuromotor training in patients undergoing ACL reconstruction on the volumetric activation of cerebral cortex regions during fMRI. in people with fMRI and ACL Injury, run by Stefano Zaffagnini at 1 site in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Lower limb injuries represent the majority of sports-related injuries, with knee injuries being among the most common. In particular, anterior cruciate ligament (ACL) injuries are considered highly devastating and career-threatening for both professional and amateur athletes. Read more about this study

Who is it for?
Ages 18 to 30 years
Conditions the study is for
fMRI, ACL Injury, Rehabilitation Exercise
What is being tested?
Effect of targeted neuromotor training in patients undergoing ACL reconstruction on the volumetric activation of cerebral cortex regions during fMRI.
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteItaly
Study dates
7 Feb 2026to Jul 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

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 30 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Patients who have undergone anterior cruciate ligament reconstruction surgery at any healthcare facility
  • Able to understand and consent, adults, who have provided informed consent to participate in the study
  • Male or female
  • Age between 18 and 30 years at the time of signing the informed consent
  • Tegner activity level > 6

Who cannot join

  • History and/or evidence of any neurological disorder or functional impairment;
  • Evidence of previous surgeries on the lower limb;
  • Inability to provide informed consent;
  • Inability to perform the tasks required by the procedure;
  • Pregnant or breastfeeding women;
  • Oncology patients;
  • Contraindications to undergoing MRI examinations.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Italy1 site, 1 recruiting
  • IRCCS Istituto Ortopedico Rizzoli

    Bologna, Bologna, 40136

    Stefano Zaffagnini, 051636 ext. 6075, stefano.zaffagnini@ior.it

    Recruiting

Other trials in Italy

About this study

Lower limb injuries represent the majority of sports-related injuries, with knee injuries being among the most common. In particular, anterior cruciate ligament (ACL) injuries are considered highly devastating and career-threatening for both professional and amateur athletes. Current surgical and rehabilitation treatments often fail to provide fully satisfactory short- and long-term outcomes. A very high risk of re-injury exists, especially in younger patients, with up to 35% experiencing a second ACL injury, alongside a significant long-term risk of early knee osteoarthritis.

Most ACL injuries are non-contact or indirect contact injuries, implicating biomechanical factors and neuromuscular control as key determinants of injury mechanisms. Recent literature shows that patients suffering a non-contact ACL injury have a higher risk of re-injury compared to those with contact injuries, suggesting a significant cognitive component in injury processing, surgery, rehabilitation, and return to sport.

Read more

Recent rehabilitation studies have introduced targeted neuromotor training designed to "rebuild" biomechanical and neuromuscular patterns to avoid mechanisms leading to re-injury. Movement quality tests are used post-training to confirm the reduction of risky biomechanical patterns, often resulting in a score indicating movement quality.

Given the brain's involvement in such injuries, pioneering studies have used functional magnetic resonance imaging (fMRI) to investigate changes in cortical brain areas following ACL injury and reconstruction. Evidence shows adaptations in both central and peripheral nervous systems, with altered sensorimotor cortex activation in patients during simple motor tasks, differing from healthy subjects. Prefrontal cortex alterations correlate with severe quadriceps muscle activation asymmetries, linking these brain patterns to post-injury return-to-sport outcomes.

However, no studies have yet evaluated the interaction between cortical activation (neural compensations) measured by fMRI and outcomes from targeted neuromotor training during ACL rehabilitation. Understanding brain activation implications is crucial for developing large-scale rehabilitation protocols to reduce the risk of a second, potentially more devastating, knee injury.

This study aims to reveal whether a neuromotor training protocol can positively influence cognitive brain areas related to human movement, particularly by reducing risky injury patterns. It will be the first to test whether dedicated neuromuscular training effectively reduces neural compensations and cortical activation related to non-automated movement, favoring automation areas important for a safe return to sport.

Patients will directly benefit from participating in the innovative neuromotor training program, with functional MRI scans conducted before training begins (post-surgery) and after training completion. Indirectly, the study will assess whether neuromotor training can adapt patient neuromotor patterns to reduce re-injury risk, ultimately benefiting future patients undergoing ACL reconstruction.

Being tested
Effect of targeted neuromotor training in patients undergoing ACL reconstruction on the volumetric activation of cerebral cortex regions during fMRI.
Medical subject headings
Anterior Cruciate Ligament Injuries

What participants receive

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

  • Effect of targeted neuromotor training in patients undergoing ACL reconstruction on the volumetric activation of cerebral cortex regions during fMRI.Other

    The effect of targeted neuromotor training in patients undergoing ACL reconstruction on the volumetric activation of cerebral cortex regions during fMRI. Differences in brain activation will be assessed between timepoint t0 (after ACL reconstruction surgery and before the start of training) and timepoint t1 (after completion of the training).

Study groups in NCT07097077
Study groupRoleWhat they receive
ACL Patients performing neuromotor trainingExperimentalNot described
Receives: Other: Effect of targeted neuromotor training in patients undergoing ACL reconstruction on the volumetric activation of cerebral cortex regions during fMRI.

What is being measured

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

  1. Variation in the volumetric activation data of the somatosensory cortex

    Variation in the volumetric activation data of the somatosensory cortex (XYZ coordinates of the peak voxel in non-overlapping brain regions) between timepoint t0 (baseline, pre-training) and timepoint t1 (post-training), measured using fMRI (BOLD sequence). This data allows for the identification of changes in brain activation attributable to the neuromotor training, supporting its effectiveness in reducing neural compensations. Based on the reference literature, a variation equal to or greater than 7 mm in the peak activation coordinates (particularly in the medio-lateral direction) will be considered clinically significant

    Measured: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies

Secondary outcomes (5)
  1. 2D kinematics (in degrees)

    2D kinematics (in degrees) measured using high-speed cameras on the frontal and sagittal planes, for example, within the 'Green Room' at the Isokinetic Medical Center in Bologna (a room equipped with synthetic turf, high-speed cameras, and an in-floor force platform, used for conducting functional movement tests (15, 26)). These data will allow for the evaluation of the interaction between neural input and biomechanical output following neuromotor training. A variation of at least 5° in key kinematic angles (e.g., knee valgus, lateral trunk tilt) will be considered significant, in accordance with thresholds reported in the literature.

    Measured: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies

  2. Ground reaction forces

    Ground reaction forces, measured, for example, using the force platform embedded in the floor of the Isokinetic Green Room. This data will allow evaluation of the interaction between neural input and the force profile exerted on the ground during functional movements. Clinically significant variations will be considered as ≥15% compared to the pre-training value in peak vertical ground reaction force (vGRF, in Newtons) and ≥0.5*BW (force normalized to body weight).

    Measured: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies

  3. MAT score

    Movement Analysis Test (MAT) score, calculated based on 2D kinematics and indicative of patient movement quality as recorded, for example, in the 'Green Room' at the Isokinetic Medical Center in Bologna. Specifically, scores of individual sub-criteria (ranging from 0 to 2), which break down movement quality through kinematic thresholds validated in the scientific literature, and the total score (sum of the 5 sub-criteria, ranging from 0 to 10) for each task will be considered. This data will allow evaluation of the interaction between somatosensory cortex activation and a composite index of movement quality across different motor tasks. Any improvement of ≥2 points in the total score (on a 0-10 scale) or ≥1 point improvement in at least three of the five sub-criteria will be considered indicative of significant functional progress, consistent with scientific validation showing a decrease in joint load (dynamic knee valgus moment) as the score increases.

    Measured: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies

  4. Changes in functional and structural connectivity of brain networks

    Changes in functional and structural connectivity of brain networks between timepoints t0 (pre-training) and t1 (post-training) assessed using DTI and resting-state (RS) fMRI techniques. A change of ≥0.1 in Fisher z-transformed correlation coefficients between key regions of the motor network (e.g., premotor area, primary motor cortex, SMA) will be considered significant, in accordance with findings reported by Criss et al.

    Measured: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies

  5. Serious and non-serious adverse events

    Serious and non-serious adverse events: Most of the events potentially associated with the procedures for outcome collection are expected to be non-serious in nature. Among non-serious adverse events, transient episodes of muscle or joint pain resulting from neuromotor training or perceived fatigue during rehabilitation sessions may occur, without leading to significant clinical consequences. Potentially serious adverse events, although unlikely, could include accidental falls during physical activity causing significant trauma that would require immediate cessation of the procedure and medical intervention.

    Measured: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies

Timeline

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

  1. First posted31 Jul 2025
  2. Study start7 Feb 2026
  3. Primary completionJul 2027 (estimated)
  4. Study completionJul 2027 (estimated)

Resources

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 N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07097077
Sponsor's protocol ID
ACL-fMRI-TNMT
Acronym
ACL-fMRI-TNMT
Status last verified
Feb 2026
First submitted
11 Jul 2025
Last updated
27 Feb 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A study testing Effect of targeted neuromotor training in patients undergoing ACL reconstruction on the volumetric activation of cerebral cortex regions during fMRI. in people with fMRI and ACL Injury, run by Stefano Zaffagnini at 1 site in Italy.

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 5 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 27 Feb 2026. 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 Italy. 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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Stefano Zaffagnini (051636 ext. 6075, stefano.zaffagnini@ior.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Variation in the volumetric activation data of the somatosensory cortex (time frame: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 27 Feb 2026.

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