Chronic Ankle Instability, CAINCT06971705
fMRI Study on Cerebral Localization and Network Mechanisms of rTMS in Chronic Ankle Instability Treatment
A study testing repetitive transcranial magnetic stimulation, rTMS and ankle stability training in people with Chronic Ankle Instability, CAI and Functional Magnetic Resonance Imaging (fMRI), run by Wuhan University at 1 site in China.
Trial summary
Chronic ankle instability (CAI) is a common sports injury that often leads to recurrent injuries and functional deficits. While conventional rehabilitation can restore ankle stability, the underlying neurophysiological mechanisms remain poorly understood, and the long-term efficacy of current treatments is limited. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Chronic Ankle Instability, CAI, Functional Magnetic Resonance Imaging (fMRI)
- What is being tested?
- repetitive transcranial magnetic stimulation, rTMS and ankle stability training
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 20 Mar 2025to 31 Oct 2026
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-60 years.
- History of at least one significant ankle sprain within the past 12 months, accompanied by inflammatory response (including pain resulting in at least one day of restricted physical activity).
- The most recent ankle sprain must have occurred more than 3 months prior to enrollment.
- Self-reported symptoms of ankle instability, defined by one or more of the following: At least two episodes of "giving way" in the affected ankle within the past 6 months; Recurrent sprains (≥2 documented sprains in the same ankle); Subjective perception of instability confirmed by any one of the following validated instruments: Ankle Instability Instrument (AII): ≥5 affirmative responses; Cumberland Ankle Instability Tool (CAIT): Score <24; Identification of Functional Ankle Instability (IdFAI): Score >11.
- Foot and Ankle Ability Measure (FAAM): Activities of Daily Living (ADL) subscale <90%; FAAM Sports subscale <80%; Foot and Ankle Outcome Score (FAOS): Scores <75% in ≥3 subcategories.
Who cannot join
- Chronic ankle instability caused by bilateral ankle sprains;
- History of lower extremity musculoskeletal or neurological surgery;
- History of lower extremity fractures;
- Acute musculoskeletal injuries in other lower extremity joints within 3 months that compromised joint integrity and function, resulting in ≥1 day of interrupted daily or sports activities;
- Concomitant severe systemic diseases (cardiac, pulmonary, hepatic, renal, etc.);
- Severe psychiatric disorders or cognitive impairments;
- Presence of metal implants or inability to tolerate MRI examinations.
- Patient refusal to participate.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Study on Precise Cerebral Localization and Network Mechanisms of Repetitive Transcranial Magnetic Stimulation in Treating Chronic Ankle Instability Based on High-resolution Functional Magnetic Resonance Imaging
Chronic ankle instability (CAI) is a common sports injury that often leads to recurrent injuries and functional deficits. While conventional rehabilitation can restore ankle stability, the underlying neurophysiological mechanisms remain poorly understood, and the long-term efficacy of current treatments is limited. This study aims to investigate the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) in combination with conventional ankle stability training for CAI and to evaluate its impact on ankle-stabilizing muscle activation and cerebral cortex excitability.
The study design is a single-center, randomized, single-blind, parallel-controlled trial. Participants with CAI will be randomly assigned to either an ankle stability training plus real rTMS group or an ankle stability training plus sham rTMS group. The primary outcome measure is the Cumberland Ankle Instability Tool (CAIT) score, which assesses the severity of ankle instability. Secondary outcomes include the Karlsson-Peterson Ankle Function Score (KPAFS), American Orthopedic Foot and Ankle Society Score (AOFAS), surface electromyography (sEMG) data, and task-based functional magnetic resonance imaging (fMRI) data. These secondary outcomes will provide a comprehensive evaluation of ankle function, muscle activation patterns, and neural activity changes.
Read more
The intervention will consist of a 4-week program, with participants receiving rTMS sessions three times per week. Each rTMS session will target key brain regions. The ankle stability training will include exercises designed to improve strength, balance, and proprioception. The sham rTMS group will receive identical ankle stability training but with a placebo rTMS protocol to ensure blinding.
Data will be collected at baseline, 2 weeks, and 4 weeks. The primary outcome, CAIT score, will be used to assess the overall improvement in ankle stability. The KPAFS and AOFAS scores will provide additional measures of ankle function and pain. sEMG data will be collected during specific functional tasks to evaluate the activation patterns of the tibialis anterior, peroneus longus, and other relevant muscles. Task-based fMRI will be used to assess changes in brain activity in motor and sensory areas before and after the intervention.
Statistical analyses will be performed using SPSS 22.0. Data will be presented as mean ± standard deviation. Between-group differences will be compared using independent samples t-tests, and overall differences across time points will be assessed via two-way repeated-measures ANOVA or mixed-effects models. Post-hoc analyses will be conducted to identify specific time points and conditions where significant differences occur.
The study timeline spans from March 2025 to December 2026, including participant recruitment, intervention implementation, data collection, and analysis, as well as manuscript drafting. This research aims to provide new insights into the neurophysiological mechanisms of CAI and to offer a novel, evidence-based approach to the rehabilitation of CAI, potentially improving long-term outcomes and reducing the risk of recurrent injuries.
- Being tested
- repetitive transcranial magnetic stimulation, rTMS, ankle stability training, Sham repetitive transcranial magnetic stimulation, SrTMS
- Keywords
- Chronic ankle instability, functional magnetic resonance imaging, repetitive transcranial magnetic stimulation, ankle stability training
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
repetitive transcranial magnetic stimulation, rTMSDevice
Participants underwent rTMS intervention prior to daily ankle stability training. The interventional targets were the key cortical brain regions identified in preliminary studies, with stimulation applied to the contralateral cortical areas corresponding to the affected ankle joint. Parameters included a figure-of-8 coil, 10 Hz frequency, 2-second stimulation duration, 8-second inter-train intervals, 60 repetitions, totaling 1,200 pulses per session, with each session lasting 10 minutes. Ankle stability training commenced within 10 minutes post-rTMS, following the same duration and intensity as the Ankle Stability Training Group + Sham rTMS Group. The treatment was conducted three times per week for a total of 4 weeks.
ankle stability trainingBehavioural
The ankle stability training protocol comprised three modalities: neuromuscular training, balance training, and proprioceptive training. Specific exercises included single-leg stance, balance pad training, heel raises, resistive ankle inversion/eversion exercises, MOBO board balance exercises, alphabet tracing (toe-writing), lateral walking, heel walking, toe walking, and jump and landing control drills. The training progressed from stable to unstable surfaces, starting at low intensity and gradually increasing in difficulty and intensity. The training was conducted three times per week for a total of 4 weeks.
Sham repetitive transcranial magnetic stimulation, SrTMSDevice
Before each session of ankle stability training, participants received sham rTMS intervention. The sham stimulation mimicked the sensory experience of real rTMS but did not produce any physiological effects.
| Study group | Role | What they receive |
|---|---|---|
| Sham rTMS plus ankle stability training | Placebo comparator | Not described Receives: Behavioral: ankle stability training; Device: Sham repetitive transcranial magnetic stimulation, SrTMS |
| rTMS plus ankle stability training | Experimental | Not described Receives: Device: repetitive transcranial magnetic stimulation, rTMS; Behavioral: ankle stability training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumberland Ankle Instability Tool score, CAIT
A self-reported questionnaire designed to assess functional ankle instability. It consists of 9 items with a total score ranging from 0 to 30, where higher scores indicate better ankle stability.
Measured: Before treatment, 2 week after treatment and 4 weeks after treatment
Secondary outcomes (4)
Karlsson-Peterson Ankle Function Score, KPAFS
The KPAFS is a scoring system used to evaluate ankle dysfunction. It includes 10 items: pain, daily activities, walking ability, need for support, squatting ability, ankle range of motion, limb positioning, limb length, limb circumference, and limb appearance. Each item is scored based on the patient's condition, with a total possible score of 100. Higher scores indicate better ankle function.
Measured: Before treatment, 2 week after treatment and 4 weeks after treatment
American Orthopedic Foot and Ankle Society score, AOFAS
The AOFAS is a widely used assessment tool for evaluating functional outcomes in foot and ankle disorders. It includes domains such as pain, function, gait, range of motion, stability, and foot alignment. The total score ranges from 0 to 100, with higher scores reflecting better foot and ankle function.
Measured: Before treatment, 2 week after treatment and 4 weeks after treatment
Surface electromyography
The surface electromyography of the tibialis anterior, gastrocnemius, and peroneus longus muscles was tested while the subjects were standing on one leg and undergoing the star excursion balance test (SEBT). The following indicators were collected:
- Time-domain analysis indicators: Root Mean Square (RMS), Integrated Electromyography (iEMG), and Averaged Electromyography (AEM).
- Frequency-domain analysis indicators: Mean Power Frequency (MPF) and Median Frequency (MF).
Measured: Before treatment and 4 weeks after treatment
fMRI
Task - related fMRI data were collected by using the affected lower limb isometric contraction combined with "single - leg standing" motor imagery.
Measured: Before treatment and 4 weeks after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2025
- Study start20 Mar 2025
- Primary completion20 May 2026 (estimated)
- Study completion31 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Ankle Instability, CAIStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wuhan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Qing Shu, Wuhan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06971705
- Sponsor's protocol ID
- 2025AFD635
- Status last verified
- May 2025
- First submitted
- 6 May 2025
- Last updated
- 18 Dec 2025
- 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 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study on Precise Cerebral Localization and Network Mechanisms of Repetitive Transcranial Magnetic Stimulation in Treating Chronic Ankle Instability Based on High-resolution Functional Magnetic Resonance Imaging
- ClinicalTrials.gov ID
- NCT06971705
- Acronym / sponsor ID
- 2025AFD635
- Keywords
- Chronic ankle instability, functional magnetic resonance imaging, repetitive transcranial magnetic stimulation, ankle stability training
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Wuhan UniversityUniversity, hospital or other
- Study start
- 20 Mar 2025 (actual)
- Primary completion
- 20 May 2026 (estimated)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 14 May 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.
Chronic ankle instability (CAI) is a common sports injury that often leads to recurrent injuries and functional deficits. While conventional rehabilitation can restore ankle stability, the underlying neurophysiological mechanisms remain poorly understood, and the long-term efficacy of current treatments is limited. This study aims to investigate the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) in combination with conventional ankle stability training for CAI and to evaluate its impact on ankle-stabilizing muscle activation and cerebral cortex excitability.
The study design is a single-center, randomized, single-blind, parallel-controlled trial. Participants with CAI will be randomly assigned to either an ankle stability training plus real rTMS group or an ankle stability training plus sham rTMS group. The primary outcome measure is the Cumberland Ankle Instability Tool (CAIT) score, which assesses the severity of ankle instability. Secondary outcomes include the Karlsson-Peterson Ankle Function Score (KPAFS), American Orthopedic Foot and Ankle Society Score (AOFAS), surface electromyography (sEMG) data, and task-based functional magnetic resonance imaging (fMRI) data. These secondary outcomes will provide a comprehensive evaluation of ankle function, muscle activation patterns, and neural activity changes.
The intervention will consist of a 4-week program, with participants receiving rTMS sessions three times per week. Each rTMS session will target key brain regions. The ankle stability training will include exercises designed to improve strength, balance, and proprioception. The sham rTMS group will receive identical ankle stability training but with a placebo rTMS protocol to ensure blinding.
Data will be collected at baseline, 2 weeks, and 4 weeks. The primary outcome, CAIT score, will be used to assess the overall improvement in ankle stability. The KPAFS and AOFAS scores will provide additional measures of ankle function and pain. sEMG data will be collected during specific functional tasks to evaluate the activation patterns of the tibialis anterior, peroneus longus, and other relevant muscles. Task-based fMRI will be used to assess changes in brain activity in motor and sensory areas before and after the intervention.
Statistical analyses will be performed using SPSS 22.0. Data will be presented as mean ± standard deviation. Between-group differences will be compared using independent samples t-tests, and overall differences across time points will be assessed via two-way repeated-measures ANOVA or mixed-effects models. Post-hoc analyses will be conducted to identify specific time points and conditions where significant differences occur.
The study timeline spans from March 2025 to December 2026, including participant recruitment, intervention implementation, data collection, and analysis, as well as manuscript drafting. This research aims to provide new insights into the neurophysiological mechanisms of CAI and to offer a novel, evidence-based approach to the rehabilitation of CAI, potentially improving long-term outcomes and reducing the risk of recurrent injuries.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sham rTMS plus ankle stability training | Placebo comparator | Behavioral: ankle stability training, Device: Sham repetitive transcranial magnetic stimulation, SrTMS |
| rTMS plus ankle stability training | Experimental | Device: repetitive transcranial magnetic stimulation, rTMS, Behavioral: ankle stability training |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age 18-60 years.
- History of at least one significant ankle sprain within the past 12 months, accompanied by inflammatory response (including pain resulting in at least one day of restricted physical activity).
- The most recent ankle sprain must have occurred more than 3 months prior to enrollment.
- Self-reported symptoms of ankle instability, defined by one or more of the following: At least two episodes of "giving way" in the affected ankle within the past 6 months; Recurrent sprains (≥2 documented sprains in the same ankle); Subjective perception of instability confirmed by any one of the following validated instruments: Ankle Instability Instrument (AII): ≥5 affirmative responses; Cumberland Ankle Instability Tool (CAIT): Score <24; Identification of Functional Ankle Instability (IdFAI): Score >11.
- Foot and Ankle Ability Measure (FAAM): Activities of Daily Living (ADL) subscale <90%; FAAM Sports subscale <80%; Foot and Ankle Outcome Score (FAOS): Scores <75% in ≥3 subcategories.
Key exclusion criteria (8 listed)
- Chronic ankle instability caused by bilateral ankle sprains;
- History of lower extremity musculoskeletal or neurological surgery;
- History of lower extremity fractures;
- Acute musculoskeletal injuries in other lower extremity joints within 3 months that compromised joint integrity and function, resulting in ≥1 day of interrupted daily or sports activities;
- Concomitant severe systemic diseases (cardiac, pulmonary, hepatic, renal, etc.);
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 |
|---|---|---|
| repetitive transcranial magnetic stimulation, rTMSParticipants underwent rTMS intervention prior to daily ankle stability training. The interventional targets were the key cortical brain regions identified in preliminary studies, with stimulation applied to the contralateral cortical areas corresponding to the affected ankle joint. Parameters included a figure-of-8 coil, 10 Hz frequency, 2-second stimulation duration, 8-second inter-train intervals, 60 repetitions, totaling 1,200 pulses per session, with each session lasting 10 minutes. Ankle stability training commenced within 10 minutes post-rTMS, following the same duration and intensity as the Ankle Stability Training Group + Sham rTMS Group. The treatment was conducted three times per week for a total of 4 weeks. | Device | rTMS plus ankle stability training |
| ankle stability trainingThe ankle stability training protocol comprised three modalities: neuromuscular training, balance training, and proprioceptive training. Specific exercises included single-leg stance, balance pad training, heel raises, resistive ankle inversion/eversion exercises, MOBO board balance exercises, alphabet tracing (toe-writing), lateral walking, heel walking, toe walking, and jump and landing control drills. The training progressed from stable to unstable surfaces, starting at low intensity and gradually increasing in difficulty and intensity. The training was conducted three times per week for a total of 4 weeks. | Behavioural | Sham rTMS plus ankle stability training, rTMS plus ankle stability training |
| Sham repetitive transcranial magnetic stimulation, SrTMSBefore each session of ankle stability training, participants received sham rTMS intervention. The sham stimulation mimicked the sensory experience of real rTMS but did not produce any physiological effects. | Device | Sham rTMS plus ankle stability training |
Primary outcome
Cumberland Ankle Instability Tool score, CAIT
Time frame: Before treatment, 2 week after treatment and 4 weeks after treatment
A self-reported questionnaire designed to assess functional ankle instability. It consists of 9 items with a total score ranging from 0 to 30, where higher scores indicate better ankle stability.
4 secondary outcomes
Karlsson-Peterson Ankle Function Score, KPAFS
Time frame: Before treatment, 2 week after treatment and 4 weeks after treatment
American Orthopedic Foot and Ankle Society score, AOFAS
Time frame: Before treatment, 2 week after treatment and 4 weeks after treatment
Surface electromyography
Time frame: Before treatment and 4 weeks after treatment
fMRI
Time frame: Before treatment and 4 weeks after treatment
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 18 Dec 2025.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing repetitive transcranial magnetic stimulation, rTMS and ankle stability training in people with Chronic Ankle Instability, CAI and Functional Magnetic Resonance Imaging (fMRI), run by Wuhan University at 1 site in China.
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 8 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: under way, not looking for participants, as of the sponsor's last update on 18 Dec 2025. 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 China. 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. Some participants in this study may receive a placebo. 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?
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?
Cumberland Ankle Instability Tool score, CAIT (time frame: Before treatment, 2 week after treatment and 4 weeks after treatment). 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 18 Dec 2025.