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.
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
- Recruiting
IRCCS Istituto Ortopedico Rizzoli
Bologna, Bologna, 40136
Stefano Zaffagnini, 051636 ext. 6075, stefano.zaffagnini@ior.it
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.
- Conditions
- fMRI, ACL Injury, Rehabilitation Exercise, Neuromuscular Control
- 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 group | Role | What they receive |
|---|---|---|
| ACL Patients performing neuromotor training | Experimental | Not 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.
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)
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
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
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
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
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.
- First posted31 Jul 2025
- Study start7 Feb 2026
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for fMRIStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stefano Zaffagnini
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS Istituto delle Scienze Neurologiche di Bologna, ISOKINETIC ER SRL
- Responsible party
- Sponsor-investigator, Stefano Zaffagnini, Istituto Ortopedico Rizzoli
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
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Functional Magnetic Resonance Signal Variations in Patients Undergoing Anterior Cruciate Ligament Reconstruction With the Application of a Dedicated Neuromotor Training
- ClinicalTrials.gov ID
- NCT07097077
- Acronym / sponsor ID
- ACL-fMRI-TNMT / ACL-fMRI-TNMT
- Conditions
- fMRI, ACL Injury, Rehabilitation Exercise, Neuromuscular Control
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Stefano ZaffagniniUniversity, hospital or other
- Collaborators
- IRCCS Istituto delle Scienze Neurologiche di Bologna, ISOKINETIC ER SRL
- Study start
- 7 Feb 2026 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 31 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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;
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 |
|---|---|---|
| Effect of targeted neuromotor training in patients undergoing ACL reconstruction on the volumetric activation of cerebral cortex regions during fMRI.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). | Other | ACL Patients performing neuromotor training |
Primary outcome
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
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
5 secondary outcomes
2D kinematics (in degrees)
Time frame: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies
Ground reaction forces
Time frame: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies
MAT score
Time frame: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies
Changes in functional and structural connectivity of brain networks
Time frame: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies
Serious and non-serious adverse events
Time frame: Between 6 and 9 months per patient based on internal analyses and ongoing scientific studies
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
Related trials for fMRI
RecruitingEarly Phase 1
Developing Transcranial Neuromodulation Protocols for Learning and Decision-Making
Normal Physiology
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
RecruitingObservational study
Structural Stressors, Reward Related Decision Making and Substance Use Risk
Substance Use Risk, Structural Stressors
Recruiting
Temporal Interference Methods for Non-invasive Deep Brain Stimulation, Study 1.3
Healthy Volunteers
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
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.
1 site in 1 country: see every site and its status.
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.