Transcutaneous Auricular Vagus Nerve Stimulation Added to Rehabilitation for Complex Regional Pain Syndrome Type I (taVNS-CRPS-I)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Complex Regional Pain Syndrome Type I
• Intervention / Treatment: Device: Active Transcutaneous Auricular Vagus Nerve Stimulation; Other: Standard Rehabilitation Program; Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Muhsin Doran, MD; Phone Number: 00905340807940; Email: muhsin-doran@hotmail.com
• Study Contact Backup: Name: muhsin doran, MD; Phone Number: 00904444548; Email: muhsin-doran@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard Rehabilitation Plus Active taVNS; 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.	Device: Active Transcutaneous Auricular Vagus Nerve Stimulation; 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.; Other: Standard Rehabilitation Program; 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.
Sham Comparator: Standard Rehabilitation Plus Sham taVNS; 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.	Other: Standard Rehabilitation Program; 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.; Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and weeks 4, 8, and 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Baseline and weeks 4, 8, and 12

Collaborators and Investigators

• Sponsor: Liv Hospital Vadistanbul
• Investigators: Principal Investigator: Muhsin Doran, Liv hospital Vadistanbul

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): February 15, 2027
• Study Completion (Estimated): February 15, 2027

Study Registration Dates

• First Submitted: July 14, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 17, 2026

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Autonomic Nervous System Diseases; Complex Regional Pain Syndromes
• Other Study ID Numbers: LIV-FTR-taVNS-CRPS1-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No