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

NCT07097077 | Recruiting

• 1 other identifier: ACL-fMRI-TNMT
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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.

Conditions

fMRI; ACL Injury; Rehabilitation Exercise; Neuromuscular Control

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (5)

• 2D kinematics (in degrees)

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

• Ground reaction forces

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

• MAT score

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

• Changes in functional and structural connectivity of brain networks

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

• Serious and non-serious adverse events

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

Study Arms (1)

ACL Patients performing neuromotor training

EXPERIMENTAL

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

Interventions

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).

ACL Patients performing neuromotor training

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stefano Zaffagnini: lead
• IRCCS Istituto delle Scienze Neurologiche di Bologna: collaborator
• ISOKINETIC ER SRL: collaborator

Study Sites (1)

IRCCS Istituto Ortopedico Rizzoli

Bologna, Bologna, 40136, Italy

RECRUITING

MeSH Terms

Conditions

Anterior Cruciate Ligament Injuries

Condition Hierarchy (Ancestors)

Knee Injuries; Leg Injuries; Wounds and Injuries

Central Study Contacts

Stefano Zaffagnini

CONTACT

051636; stefano.zaffagnini@ior.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Full Professor Medicine and Surgery, University of Bologna

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: July 31, 2025
• Study Start: February 7, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

IT (1)