Complex Regional Pain Syndrome Type ItaVNS-CRPS-INCT07711392
Transcutaneous Auricular Vagus Nerve Stimulation Added to Rehabilitation for Complex Regional Pain Syndrome Type I
A study testing Active Transcutaneous Auricular Vagus Nerve Stimulation and Standard Rehabilitation Program in people with Complex Regional Pain Syndrome Type I, run by Liv Hospital Vadistanbul.
Trial summary
This randomized, participant- and assessor-blinded, sham-controlled study will evaluate the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) added to standard rehabilitation in adults with complex regional pain syndrome type I (CRPS-I) affecting the hand or upper extremity. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Complex Regional Pain Syndrome Type I
- What is being tested?
- Active Transcutaneous Auricular Vagus Nerve Stimulation and Standard Rehabilitation Program
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 15 Jul 2026to 15 Feb 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of complex regional pain syndrome type I according to the Budapest diagnostic criteria
- Age 18 to 65 years
- CRPS type I affecting the hand following a traumatic cause, including surgery, fracture, and/or immobilization of the hand or upper extremity
- Willingness to participate in the study and provision of written informed consent
Who cannot join
- Diagnosis of complex regional pain syndrome type II
- CRPS type I developing after stroke
- Acute or post-acute rehabilitation following hand tendon repair
- Presence of a comorbid condition that may substantially affect functional status or health-related quality of life, including decompensated heart failure, chronic kidney failure, or malignancy
- Arthritis affecting the hand
- Acute arterial or venous thrombosis of the upper extremity
- History of arterial or venous injury of the upper extremity
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Effectiveness of Transcutaneous Auricular Vagus Nerve Stimulation Added to Standard Rehabilitation in Patients With Complex Regional Pain Syndrome Type I: A Randomized Controlled Trial
This randomized, participant- and assessor-blinded, sham-controlled study will evaluate the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) added to standard rehabilitation in adults with complex regional pain syndrome type I (CRPS-I) affecting the hand or upper extremity.
A total of 20 participants will be randomly assigned to two parallel groups. Both groups will receive the same standard rehabilitation program 5 days per week for 4 weeks. In addition, the experimental group will receive active taVNS, while the control group will receive sham taVNS for 30 minutes per session over the same 4-week period.
The primary outcome is change in pain intensity measured using the Numerical Rating Scale. Secondary outcomes include CRPS clinical severity, hand and wrist circumference, hand function and activities of daily living, health-related quality of life, anxiety and depression symptoms, and perceived stress. Assessments will be performed at baseline, at the end of treatment at week 4, and during follow-up at weeks 8 and 12.
Read the detailed description
Complex regional pain syndrome type I is a disabling condition that may develop after trauma, fracture, surgery, or immobilization. It is characterized by pain that is disproportionate to the initial injury and may be accompanied by sensory, autonomic, motor, edema, and trophic abnormalities. Despite multidisciplinary rehabilitation and pharmacological treatment, some patients continue to experience persistent pain and functional impairment.
Transcutaneous auricular vagus nerve stimulation is a non-invasive neuromodulation method that stimulates auricular regions innervated by the vagus nerve. It may affect pain processing, autonomic nervous system regulation, central sensitization, and neuroinflammatory mechanisms that may contribute to CRPS-I. Evidence regarding the clinical effectiveness of taVNS in this patient population remains limited.
The primary objective of this study is to determine whether active taVNS added to standard rehabilitation provides greater pain reduction than sham taVNS added to the same rehabilitation program. Secondary objectives are to compare the effects of the interventions on CRPS clinical severity, edema-related hand and wrist circumference measurements, hand function, activities of daily living, health-related quality of life, anxiety and depression symptoms, and perceived stress.
Participants will be randomly allocated in a 1:1 ratio to standard rehabilitation plus active taVNS or standard rehabilitation plus sham taVNS. Both groups will receive an identical 4-week rehabilitation program. Active and sham stimulation will be delivered with the same session duration and frequency. Participants and the outcomes assessor will be blinded to group allocation. The physiotherapist administering the stimulation will be aware of the allocation and will not participate in outcome assessments. Treatment effects and their persistence will be evaluated at weeks 4, 8, and 12.
- Conditions
- Complex Regional Pain Syndrome Type I
- Being tested
- Active Transcutaneous Auricular Vagus Nerve Stimulation, Sham Transcutaneous Auricular Vagus Nerve Stimulation, Standard Rehabilitation Program
- Medical subject headings
- Complex Regional Pain Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Transcutaneous Auricular Vagus Nerve StimulationDevice
Active transcutaneous auricular vagus nerve stimulation will be applied to the auricular concha region for 30 minutes per session, 5 days per week for 4 weeks, for a total of 20 sessions. Stimulation intensity will be individually adjusted to produce a tolerable paresthesia without pain. The intervention will be administered by a trained physiotherapist in addition to the standard rehabilitation program.
Sham Transcutaneous Auricular Vagus Nerve StimulationDevice
Sham transcutaneous auricular vagus nerve stimulation will be administered using the same device, session duration, and treatment schedule as active taVNS: 30 minutes per session, 5 days per week for 4 weeks, for a total of 20 sessions. The electrode placement and/or stimulation parameters will be configured according to a prespecified sham protocol intended not to produce therapeutic vagal stimulation. The sham intervention will be administered by a trained physiotherapist in addition to the standard rehabilitation program.
Standard Rehabilitation ProgramOther
All participants will receive the standard physical therapy and rehabilitation program routinely used in our clinic for patients with CRPS-I and based on current literature. The program will include contrast baths, transcutaneous electrical nerve stimulation, desensitization techniques, passive and active range-of-motion exercises, isometric and isotonic strengthening exercises, progressive loading exercises, hand dexterity and coordination activities, and functional training focused on activities of daily living. The rehabilitation program will be administered 5 days per week for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Standard Rehabilitation Plus Active taVNS | Experimental | Participants will receive a standard rehabilitation program 5 days per week for 4 weeks. The program will include contrast baths, transcutaneous electrical nerve stimulation, heat therapy, desensitization techniques, passive and active range-of-motion exercises, strengthening, progressive loading, hand dexterity and coordination activities, and functional training. In addition, active transcutaneous auricular vagus nerve stimulation will be administered for 30 minutes per session, 5 days per week for 4 weeks, for a total of 20 sessions. Receives: Device: Active Transcutaneous Auricular Vagus Nerve Stimulation; Other: Standard Rehabilitation Program |
| Standard Rehabilitation Plus Sham taVNS | Sham comparator | Participants will receive the same standard rehabilitation program 5 days per week for 4 weeks, including contrast baths, transcutaneous electrical nerve stimulation, heat therapy, desensitization techniques, passive and active range-of-motion exercises, strengthening, progressive loading, hand dexterity and coordination activities, and functional training. In addition, sham transcutaneous auricular vagus nerve stimulation will be administered for 30 minutes per session, 5 days per week for 4 weeks, for a total of 20 sessions, using a prespecified sham protocol not expected to produce therapeutic vagal stimulation. Receives: Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation; Other: Standard Rehabilitation Program |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pain Intensity Assessed With the Numerical Rating Scale
Pain intensity will be assessed using an 11-point Numerical Rating Scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. Higher scores indicate greater pain intensity. Change from baseline will be evaluated at weeks 4, 8, and 12.
Measured: Baseline and weeks 4, 8, and 12
Secondary outcomes (4)
Change in Complex Regional Pain Syndrome Severity Assessed With the CRPS Severity Score
Clinical severity of complex regional pain syndrome will be assessed using the CRPS Severity Score, which evaluates CRPS-related symptoms and clinical signs. The total score ranges from 0 to 16, with higher scores indicating greater disease severity. Change from baseline will be evaluated at weeks 4, 8, and 12.
Measured: Baseline and weeks 4, 8, and 12
Change in Hand Circumference
Hand circumference of the affected extremity will be measured in centimeters at a standardized anatomical reference point using a measuring tape. Three consecutive measurements will be obtained at each assessment, and the mean value will be recorded. Higher values indicate greater hand circumference. Change from baseline will be evaluated at weeks 4, 8, and 12.
Measured: Baseline and weeks 4, 8, and 12
Change in Wrist Circumference
Wrist circumference of the affected extremity will be measured in centimeters at a standardized anatomical reference point using a measuring tape. Three consecutive measurements will be obtained at each assessment, and the mean value will be recorded. Higher values indicate greater wrist circumference. Change from baseline will be evaluated at weeks 4, 8, and 12.
Measured: Baseline and weeks 4, 8, and 12
Change in Hand Function Assessed With the Duruöz Hand Index
Hand function and difficulty performing daily manual activities will be assessed using the 18-item Duruöz Hand Index. Each item is scored from 0 to 5, producing a total score ranging from 0 to 90. Higher scores indicate greater hand-related functional disability. Change from baseline will be evaluated at weeks 4, 8, and 12.
Measured: Baseline and weeks 4, 8, and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2026
- Study start15 Jul 2026 (estimated)
- Primary completion15 Feb 2027 (estimated)
- Study completion15 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Complex Regional Pain Syndrome Type IStudies 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
- Model description
- Participants will be randomly assigned in a 1:1 ratio to two parallel groups: standard rehabilitation plus active transcutaneous auricular vagus nerve stimulation or standard rehabilitation plus sham transcutaneous auricular vagus nerve stimulation. Participants will remain in their assigned groups throughout the study, with no crossover between groups.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Liv Hospital Vadistanbul
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Muhsin Doran, Liv Hospital Vadistanbul
- Investigators
- Muhsin Doran, Principal investigator, Liv Hospital Vadistanbul
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07711392
- Sponsor's protocol ID
- LIV-FTR-taVNS-CRPS1-2026-01
- Acronym
- taVNS-CRPS-I
- Status last verified
- Jul 2026
- First submitted
- 14 Jul 2026
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared because no external IPD-sharing procedure has been established for this study. Study findings will be reported only in aggregate form to protect participant confidentiality.
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Transcutaneous Auricular Vagus Nerve Stimulation Added to Standard Rehabilitation in Patients With Complex Regional Pain Syndrome Type I: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07711392
- Acronym / sponsor ID
- taVNS-CRPS-I / LIV-FTR-taVNS-CRPS1-2026-01
- Conditions
- Complex Regional Pain Syndrome Type I
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Liv Hospital VadistanbulUniversity, hospital or other
- Study start
- 15 Jul 2026 (estimated)
- Primary completion
- 15 Feb 2027 (estimated)
- Study completion
- 15 Feb 2027 (estimated)
- First posted
- 17 Jul 2026 (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.
This randomized, participant- and assessor-blinded, sham-controlled study will evaluate the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) added to standard rehabilitation in adults with complex regional pain syndrome type I (CRPS-I) affecting the hand or upper extremity.
A total of 20 participants will be randomly assigned to two parallel groups. Both groups will receive the same standard rehabilitation program 5 days per week for 4 weeks. In addition, the experimental group will receive active taVNS, while the control group will receive sham taVNS for 30 minutes per session over the same 4-week period.
The primary outcome is change in pain intensity measured using the Numerical Rating Scale. Secondary outcomes include CRPS clinical severity, hand and wrist circumference, hand function and activities of daily living, health-related quality of life, anxiety and depression symptoms, and perceived stress. Assessments will be performed at baseline, at the end of treatment at week 4, and during follow-up at weeks 8 and 12.
Detailed description
Complex regional pain syndrome type I is a disabling condition that may develop after trauma, fracture, surgery, or immobilization. It is characterized by pain that is disproportionate to the initial injury and may be accompanied by sensory, autonomic, motor, edema, and trophic abnormalities. Despite multidisciplinary rehabilitation and pharmacological treatment, some patients continue to experience persistent pain and functional impairment.
Transcutaneous auricular vagus nerve stimulation is a non-invasive neuromodulation method that stimulates auricular regions innervated by the vagus nerve. It may affect pain processing, autonomic nervous system regulation, central sensitization, and neuroinflammatory mechanisms that may contribute to CRPS-I. Evidence regarding the clinical effectiveness of taVNS in this patient population remains limited.
The primary objective of this study is to determine whether active taVNS added to standard rehabilitation provides greater pain reduction than sham taVNS added to the same rehabilitation program. Secondary objectives are to compare the effects of the interventions on CRPS clinical severity, edema-related hand and wrist circumference measurements, hand function, activities of daily living, health-related quality of life, anxiety and depression symptoms, and perceived stress.
Participants will be randomly allocated in a 1:1 ratio to standard rehabilitation plus active taVNS or standard rehabilitation plus sham taVNS. Both groups will receive an identical 4-week rehabilitation program. Active and sham stimulation will be delivered with the same session duration and frequency. Participants and the outcomes assessor will be blinded to group allocation. The physiotherapist administering the stimulation will be aware of the allocation and will not participate in outcome assessments. Treatment effects and their persistence will be evaluated at weeks 4, 8, and 12.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomly assigned in a 1:1 ratio to two parallel groups: standard rehabilitation plus active transcutaneous auricular vagus nerve stimulation or standard rehabilitation plus sham transcutaneous auricular vagus nerve stimulation. Participants will remain in their assigned groups throughout the study, with no crossover between groups.
| Arm | Type | Receives |
|---|---|---|
| Standard Rehabilitation Plus Active taVNS | Experimental | Device: Active Transcutaneous Auricular Vagus Nerve Stimulation, Other: Standard Rehabilitation ProgramParticipants will receive a standard rehabilitation program 5 days per week for 4 weeks. The program will include contrast baths, transcutaneous electrical nerve stimulation, heat therapy, desensitization techniques, passive and active range-of-motion exercises, strengthening, progressive loading, hand dexterity and coordination activities, and functional training. In addition, active transcutaneous auricular vagus nerve stimulation will be administered for 30 minutes per session, 5 days per week for 4 weeks, for a total of 20 sessions. |
| Standard Rehabilitation Plus Sham taVNS | Sham comparator | Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation, Other: Standard Rehabilitation ProgramParticipants will receive the same standard rehabilitation program 5 days per week for 4 weeks, including contrast baths, transcutaneous electrical nerve stimulation, heat therapy, desensitization techniques, passive and active range-of-motion exercises, strengthening, progressive loading, hand dexterity and coordination activities, and functional training. In addition, sham transcutaneous auricular vagus nerve stimulation will be administered for 30 minutes per session, 5 days per week for 4 weeks, for a total of 20 sessions, using a prespecified sham protocol not expected to produce therapeutic vagal stimulation. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of complex regional pain syndrome type I according to the Budapest diagnostic criteria
- Age 18 to 65 years
- CRPS type I affecting the hand following a traumatic cause, including surgery, fracture, and/or immobilization of the hand or upper extremity
- Willingness to participate in the study and provision of written informed consent
Key exclusion criteria (7 listed)
- Diagnosis of complex regional pain syndrome type II
- CRPS type I developing after stroke
- Acute or post-acute rehabilitation following hand tendon repair
- Presence of a comorbid condition that may substantially affect functional status or health-related quality of life, including decompensated heart failure, chronic kidney failure, or malignancy
- Arthritis affecting the hand
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 |
|---|---|---|
| Active Transcutaneous Auricular Vagus Nerve StimulationActive transcutaneous auricular vagus nerve stimulation will be applied to the auricular concha region for 30 minutes per session, 5 days per week for 4 weeks, for a total of 20 sessions. Stimulation intensity will be individually adjusted to produce a tolerable paresthesia without pain. The intervention will be administered by a trained physiotherapist in addition to the standard rehabilitation program. | Device | Standard Rehabilitation Plus Active taVNS |
| Sham Transcutaneous Auricular Vagus Nerve StimulationSham transcutaneous auricular vagus nerve stimulation will be administered using the same device, session duration, and treatment schedule as active taVNS: 30 minutes per session, 5 days per week for 4 weeks, for a total of 20 sessions. The electrode placement and/or stimulation parameters will be configured according to a prespecified sham protocol intended not to produce therapeutic vagal stimulation. The sham intervention will be administered by a trained physiotherapist in addition to the standard rehabilitation program. | Device | Standard Rehabilitation Plus Sham taVNS |
| Standard Rehabilitation ProgramAll participants will receive the standard physical therapy and rehabilitation program routinely used in our clinic for patients with CRPS-I and based on current literature. The program will include contrast baths, transcutaneous electrical nerve stimulation, desensitization techniques, passive and active range-of-motion exercises, isometric and isotonic strengthening exercises, progressive loading exercises, hand dexterity and coordination activities, and functional training focused on activities of daily living. The rehabilitation program will be administered 5 days per week for 4 weeks. | Other | Standard Rehabilitation Plus Active taVNS, Standard Rehabilitation Plus Sham taVNS |
Primary outcome
Change in Pain Intensity Assessed With the Numerical Rating Scale
Time frame: Baseline and weeks 4, 8, and 12
Pain intensity will be assessed using an 11-point Numerical Rating Scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. Higher scores indicate greater pain intensity. Change from baseline will be evaluated at weeks 4, 8, and 12.
4 secondary outcomes
Change in Complex Regional Pain Syndrome Severity Assessed With the CRPS Severity Score
Time frame: Baseline and weeks 4, 8, and 12
Change in Hand Circumference
Time frame: Baseline and weeks 4, 8, and 12
Change in Wrist Circumference
Time frame: Baseline and weeks 4, 8, and 12
Change in Hand Function Assessed With the Duruöz Hand Index
Time frame: Baseline and weeks 4, 8, and 12
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 17 Jul 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared because no external IPD-sharing procedure has been established for this study. Study findings will be reported only in aggregate form to protect participant confidentiality.
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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.
Muhsin Doran principal investigator
Liv Hospital Vadistanbul
Questions about this trial
What is this clinical trial studying?
A study testing Active Transcutaneous Auricular Vagus Nerve Stimulation and Standard Rehabilitation Program in people with Complex Regional Pain Syndrome Type I, run by Liv Hospital Vadistanbul.
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 4 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: opening soon, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
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?
Contact Muhsin Doran, MD (00905340807940, muhsin-doran@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pain Intensity Assessed With the Numerical Rating Scale (time frame: Baseline and weeks 4, 8, and 12). 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 17 Jul 2026.