Pain Neuroscience Education and Vagus Nerve Stimulation on Recovery in Individuals With Rheumatoid Arthritis

NCT07274124 | Not Yet Recruiting

• 1 other identifier: E-10840098-202.3.02-7253
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

In the context of this randomized controlled study, patients who are diagnosed with Rheumatoid arthritis in Cerrahpaşa Faculty of Medicine Hospital, will be taken into a rehabilitation program by a qualified physiotherapist to improve their pain, pain perception, inflammatory markers and quality of life, with one of the pain neuroscience education, vagal nerve stimulation and traditional exercise interventions. The results of each intervention method will be analyzed and compared at the end of the 8 weeks study protocol.

Conditions

Rheumatic Diseases; Rheumatoid Arthritis (RA)

Keywords

rheumatoid arthritis; pain neuroscience education; vagal nerve stimulation; exercise

Outcome Measures

Primary Outcomes (2)

• Pain Catastrophizing Scale

  13-item questionnaire, based on personal feedback, assesses the severity of patients' reactions to pain on a scale of 0-4. The validity and reliability of the questionnaire in Turkish has been established.

  8 weeks

• Disease Activity Score-28 (DAS28)

  Assesses disease activity in 28 different joints. Blood draws will be performed by a specialist physician who diagnoses patients, conducts regular checkups, and then refers suitable patients to a physical therapist. A score below 2.6 indicates the disease is in remission; scores between 2.6 and 3.1 indicate low disease activity; scores between 3.1 and 5.1 indicate moderate disease activity; and scores above 5.1 indicate high disease activity.

  8 weeks

Secondary Outcomes (10)

• Demographic Information Form

  At the beginning only

• Mcgill Pain Questionnaire Short Form

  8 weeks

• Pain Algometry

  8 weeks

• Pain Coping Inventory

  8 weeks

• Tampa Kinesiophobia Scale

  8 weeks

Study Arms (3)

Pain Neuroscience Education + Structured Exercise

EXPERIMENTAL

The PNE method will be applied simultaneously with exercise. Training will begin after the first session, which includes a face-to-face assessment. On the first day, a PowerPoint presentation will introduce the patient about pain anatomy, physiology, factors affecting pain, and central and peripheral sensitization. The topic of pain will be introduced, and the patient will be informed about the process. Pain mechanisms will be reviewed using video explanations, visual aids, and animations, information will be provided on what physical activity is and its effects on pain, patients will be asked their opinions on exercise, suggestions for physical daily, living activities will be given such as increasing activity, using stairs, limiting screen time type of suggestions will be thought to the patient and the patient's wishes and goals will be questioned in the further sessions. Each session will last 30 minutes and 16 education sessions will be completed in total.

Other: Pain Neuroscience Education; Other: Structured Exercises

Vagal Nerve Stimulation + Structured Exercise

EXPERIMENTAL

Will be applied with the non-invasive taVNS-Research (tVNS®) device, which is the only safe auricular vagus stimulation device approved by the Ministry of Health in Türkiye and is used in various diseases such as headache, epilepsy, and fibromyalgia. Electrodes will be placed on the left auricular cavum conchae using two carbon-impregnated silicone electrodes to reduce the risk of cardiac side effects. Vagal nerve stimulation will be administered twice a week for 8 weeks, with a total of 16 supervised sessions. During this period, the home exercise intervention that patients are asked to perform will continue. Following the initial evaluation, the exercises will be taught to the patient, and the first nerve stimulation session will be performed. Current intensity will be adjusted according to the patient tolerance-threshold value, and this value will be recorded for each session.

Other: Vagal Nerve Stimulation; Other: Structured Exercises

Structured Exercise

ACTIVE COMPARATOR

The Structured exercise intervention, specifically for individuals with RA and designed to target painful areas, will be implemented in the form of home exercises for all three groups, twice a week for 8 weeks. The exercise program will primarily consist of warm-up, basic exercise, and a cool-down period. Aerobic, strengthening, flexibility, breathing, and hand exercises will be planned based on EULAR recommendations. The warm-up period will begin with flexibility and range of motion exercises, followed by calisthenic and therapeutic endurance and strengthening exercises, and the session will ended with diaphragmatic breathing and hand exercises during the cool-down period. Additionally, walking activity will be recommended for at least two days per week.

Other: Structured Exercises

Interventions

Pain Neuroscience Education OTHER

Many sources in the literature draw attention to patient education as the first stage of treatment and the most common educational technique that focuses on the perception, mechanism and modulation of pain is known as Pain Neuroscience Education (PNE). Patients in this group will take educational sessions about the pain, facilitators of pain, the factors affecting the pain perception and how to deal with chronic pain in rheumatoid arthritis with the help of power point presentations, animation videos, pictures and drawings. Intervention will last for 8 weeks, 2 times per week, in total 16 sessions will be completed. Each session will last 30 minutes in average and at the same time, patients will be advised to perform the given home exercises for 2 times per week. Assessments will be performed before and after the intervention.

Pain Neuroscience Education + Structured Exercise

Vagal Nerve Stimulation OTHER

Vagus nerve (cranial nerve X) is the longest and most widely distributed cranial nerve containing sensory, motor, and parasympathetic fibers. It plays an important role in the regulation of cardiovascular, respiratory, immune, endocrine, and autonomic systems, as well as homeostasis. Participants with rheumatoid arthritis will be taken into stimulation sessions for 2 times per week for continuous 8 weeks. Assessments will be performed before study and after the 16 sessions are completed. Since the literature has missing knowledge about the effects of Vagal nerve stimulation in rheumatoid arthritis, the results will highlight the effects on pain and inflammatory markers in this population. Current will be given from the left ear/transauricular area to prevent the side effects in the sessions.

Vagal Nerve Stimulation + Structured Exercise

Structured Exercises OTHER

Structured exercise planned in this study is based on the principles and suggestions of EULAR, by consisting warm-up, basic exercise and warm up sessions by combining different exercise types like aerobic, strengthening flexibility, breathing and definitely by including hand specific exercises. Participants in all three groups will be educated in the first session about the exercises to prevent wrong application and injuries. Afterwards, all groups will continue to their exercises at the home setting. An exercise diary will be asked from patients to control if they continue to their exercises regularly for 2 times for 8 weeks.

Pain Neuroscience Education + Structured Exercise; Structured Exercise; Vagal Nerve Stimulation + Structured Exercise

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals who were diagnosed with RA at least one year ago,
• Ages of 18 and 65,
• Have been experiencing pain for three months or more,
• Score 24 or higher on the Mini Mental State Examination (MMSE), and can follow instructions will be included in the study.

You may not qualify if:

• Individuals under 18 years of age,
• Reporting acute pain or pain from injury,
• Having a history of surgery within the last year,
• Having a score of \<24 on the MMSE,
• Having any of the cerebrovascular disease, cardiovascular disease, symptomatic coronary artery disease, myocardial infarction, congestive heart failure, or uncontrolled hyper/hypotension,
• History of vagotomy surgery, or having an implanted electrical/neurostimulator device will not be included in the study.

Sponsors & Collaborators

• Medipol University: lead
• Istanbul University - Cerrahpasa: collaborator

Study Sites (1)

Cerrahpaşa Faculty of Medicine Hospital

Istanbul, Fatih, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Rheumatic Diseases; Arthritis, Rheumatoid; Motor Activity

Interventions

Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Arthritis; Joint Diseases; Autoimmune Diseases; Immune System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Officials

• Simay AKDEMİR, MSc. Phd Candidate/Lec.

  İstanbul University-Cerrahpaşa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Simay AKDEMİR, MSc. Phd Candidate/Lec.

CONTACT

+905347032126; simay.akdemir@medipol.edu.tr

Ela TARAKCI, Prof. Dr.

CONTACT

+905422175730; etarakci@iuc.edu.tr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patients who are taken into one of the three intervention groups will not have any idea or information about the interventions being performed in other groups.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MSc. Phd Candidate, Lecturer Physical Therapist

Model Details: The study will be conducted using a randomized, controlled, prospective design. Thirty-six individuals diagnosed with RA at the Department of Rheumatology at Cerrahpaşa Faculty of Medicine Hospital will be included in the study. Following the physician referral, individuals who meet the inclusion criteria will be divided into three equal groups (12 in each), by using block randomization by the "randomizer.org" website, and the number of cases will be calculated using the "GPower" application. Demographic information will be collected before the study begins, and all participants will be informed in advance of the study's purpose, duration, and content, as well as the voluntary nature of their participation with an informed consent form. After the initial assessment, the intervention will last for 8 weeks and consist of three groups: "Pain Neuroscience Education-PNE + Structured Exercise," "Transauricular Vagus Nerve Stimulation-tVNS + Structured Exercise," and "Structured Exercise."

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 10, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: December 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)