EFFECT OF TRANSCUTANEOUS ELECTRONEURO-STIMULATION OF THE VAGUS NERVE ON JOINT PAIN SEQUELAE OF CHIKUNGUNYA FEVER IN THE LOWER LIMBS

April 4, 2026 updated by: Luiza Moneta Araújo, Universidade Federal de Pernambuco
This study aims to evaluate the efficacy of transcutaneous electrical nerve stimulation (taVNS) in reducing chronic lower limb joint pain in individuals with sequelae of Chikungunya fever. Post-Chikungunya chronic pain is a prevalent and disabling condition associated with persistent inflammation, neuroimmune alterations, and central sensitization mechanisms, which negatively impact functionality and quality of life. Given the lack of specific treatments with established efficacy, vagal neuromodulation emerges as a promising approach. This is a randomized, controlled, parallel, three-arm clinical trial involving adults with chronic joint pain lasting at least three months after Chikungunya infection. Participants will be randomly assigned (1:1:1) to one of three groups: taVNS, peripheral TENS (active control), or sham stimulation (placebo). The study will use a double-blind design for both participants and evaluators. The interventions will take place twice a week for three weeks, totaling six 30-minute sessions. taVNS will be applied to the superior concha of the left ear using standardized parameters, with intensity adjusted to a comfortable sensory threshold. The active control group will receive TENS on the painful joint, while the sham group will receive auricular stimulation without effective vagal activation. The primary outcome will be the change in pain intensity, assessed using the Visual Analogue Scale. Secondary outcomes will include quality of life (SF-36), pressure pain threshold, joint temperature, and functional performance (Timed Up and Go). The analysis will follow the linear mixed-effects using repeated measures models. The results are expected to strengthen the evidence for taVNS as a non-pharmacological intervention for managing chronic post-Chikungunya pain.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
51

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • Pernambuco
      • Recife, Pernambuco, Brazil, 50670-420
        • Federal University of Pernambuco - Department of Physiotherapy, Electrophototherapy Laboratory

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • People of either sex who are over 18 years of age, Clinical diagnosis of Chikungunya confirmed by laboratory test and/or medical report; Chronic joint pain in one or more lower limb joints lasting at least 3 months after infection; Ability to ambulate independently or with assistive devices; Intact skin integrity in the auricular region and areas of electrode placement; Residing in the state of Pernambuco.

Exclusion Criteria:

  • Neurological disorders; Decompensated cardiorespiratory diseases; Pre-existing systemic rheumatic diseases prior to Chikungunya infection; History of seizures or epilepsy; Presence of implanted electronic devices (e.g., pacemakers); Pregnancy; Orofacial or ear pain; Skin lesions, infections, or impaired sensation at stimulation sites; Thrombophlebitis, ischemic or ulcerated areas; Neoplasms; Use of medications or substances that increase seizure risk; Current participation in other physiotherapy treatments during the study period; Conditions that prevent attendance at the study site.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group 1
Individuals receiving a TENS current application protocol in the superior concha of the left ear, the outer ear area innervated by the auricular branch of the vagus nerve. They recive the tVNS intervention.
Device: Transcutaneous vagus nerve electrical stimulation
The transcutaneous vagus nerve electrical stimulations is a non-pharmacological analgesic intervention for the treatment of pain and has been shown to be beneficial in epilepsy, depression, chronic pain and inflammatory diseases.
Other Names:
  • taVNS
Active Comparator: Group 2
Individuals receiving a TENS current application protocol in a painful lower limb joint (knee or ankle)
Device: Transcutaneous eletrical nerve stimuation
The transcutaneous eletrical nerve stimulation is another non-pharmacological analgesic intervention for the treatment of chronic and acute pain, it has studies about it effectiveness in this types of pain for 50 years.
Other Names:
  • Peripheral TENS
Sham Comparator: G3
individuals receiving a TENS current in the left ear lobe only, an area not innervated by the auricular branch of the vagus nerve, without effective vagal activation
Device: Transcutaneous electrical nerve stimulation
The sham stimulation mimics the sensory experience of active stimulation without producing therapeutic neuromodulatory effects.
Other Names:
  • Sham taVNS

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Visual Analogue Scale
Time Frame: Baseline and immediately after the 3-week intervention period
The visual analog pain scale (VAS) is used, a one-dimensional instrument for assessing pain intensity. It is a line whose ends are numbered 0-10. One end of the line is marked "no pain" and the other "worst pain imaginable".
Baseline and immediately after the 3-week intervention period

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Quality of life (SF-36)
Time Frame: Baseline and post-intervention (3 weeks)
The 36-item Medical Outcomes Study Short-Form Health Survey (SF-36) is used to assess quality of life. It consists of 36 items covering 8 domains: Functioning (10 items), physical aspects (4 items), pain (2 items), general health (5 items), vitality (4 items), social aspects (2 items), emotional aspects (3 items), mental health (5 items).
Baseline and post-intervention (3 weeks)
Pressure Pain Threshold
Time Frame: Baseline and post-intervention (3 weeks)
A KRATOS pressure algometer (PA), model DDK electronic, with a flat, circular metal probe with a diameter of 01 cm and a pressure in kilogram force (kgf) is used to measure the pressure pain threshold.
Baseline and post-intervention (3 weeks)
Digital thermography
Time Frame: Baseline and post-intervention (3 weeks)
Joint temperature will be assessed using infrared thermography under controlled environmental conditions to evaluate changes associated with inflammation.
Baseline and post-intervention (3 weeks)
Timed Up and Go
Time Frame: Baseline and post-intervention (3 weeks)
An Android smartphone with the MOMENTUM SCIENCE app installed is used to assess the dynamic balance. The smartphone is attached to the lumbar region between L3 and L5 with a Velcro strap to hold it in place and the Time UP and Go (TUG) test is performed.
Baseline and post-intervention (3 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universidade Federal de Pernambuco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Aguiar-Santos M, et al. Spatial analysis of the incidence of Chikungunya fever and associated socioeconomic, demographic and vector infestation factors in municipalities of Pernambuco, Brazil, 2015-2021. 2023;26. Badran BW, et al. Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: a concurrent taVNS/fMRI study and review. Brain Stimul. 2018;11(3):492-500. Botha C, et al. Modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity. Gut. 2015;64(4):611-617. Brazil Ministry of Health. Health Surveillance Guide. 5th ed. Brasília (DF): Ministry of Health; 2022. Butt MF, et al. The anatomical basis for transcutaneous auricular vagus nerve stimulation. J Anat. 2020;236(4):588-611. Irigoyen MC, et al. Revisiting sympathetic nervous system physiology: what's new? Rev Bras Hipertens. 2014;24(2):9-15. Crossman AR, Neary D. Neuroanatomy: An Illustrated Colour Text. Rio de Janeiro: Elsevier; 1997. Farmer AD, Aziz Q. Vagally mediated analgesia: breath-holding during exhalation as a simple manipulation to reduce pain perception. Pain Med. 2015;16(12):2417-2418. Hamer HM, Bauer S. Lessons learned from transcutaneous vagus nerve stimulation (tVNS). Epilepsy Behav. 2019;83-84. Hartley S, et al. Noninvasive vagus nerve stimulation: a new therapeutic approach for pharmacoresistant restless legs syndrome. Sleep Med. 2023;26(3):629-637. Lopes N, Nozawa C, Linhares REC. General characteristics and epidemiology of emerging arboviruses in Brazil. Rev Pan-Amaz Saude. 2014;5(3). Martinez JE, Grassi DC, Marques LG. Analysis of the applicability of three pain assessment instruments in different care units: outpatient, ward and emergency. Rev Bras Reumatol. 2011;51(4):299-308. Mesquita R, et al. Brazilian-Portuguese version of the SF-36: a reliable and valid quality of life out

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 4, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 10, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 15, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 4, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 4, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 13, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 83524324.0.0000.5208

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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