Transcutaneous Vagus Nerve Stimulation as a Complementary Therapy to Exercise in Chronic Fatigue (PAF-tVNS)

May 5, 2026 updated by: Centre Hospitalier Universitaire de Saint Etienne

Transcutaneous Vagus Nerve Stimulation as a Complementary Therapy to Exercise in Chronic Fatigue: Single-center, Controlled, Randomized, Blinded Study

Chronic fatigue is enhanced by adapted physical activity (APA) programs. Patients consulting on St Etienne hospital and suffering from fibromyalgia and long Covid benefit from a 4-6 week APA program, with 2 sessions per week. While most patients are improved by these exercise-training programs, for some the benefits remain very modest, and patients describe persistent fatigue. The literature unanimously describes the necessity of longer APA protocols (8-12 weeks, 2-3 sessions/week) for fatigue reduction in fibromyalgia and long Covid. However, it seems difficult to adhere to an optimal program as described in the literature for these fatigued patients. The investigators want to test a device that would both reduce fatigue and improve recovery between APA sessions, in order to gradually reach the recommendations for APA practice. Transcutaneous vagal nerve stimulation (tVNS) seems to be a promising approach. Thus, combining an APA intervention with a tVNS protocol could potentiate the expected and now well-known effect of exercise.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
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.
60

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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Saint-Etienne, France, 42055
        • Recruiting
        • CENTRE HOSPITALIER DE SAINT-ETIENNE
        • Principal Investigator:
          • David HUPIN, MD
        • Sub-Investigator:
          • Léonard FEASSON, MD PhD
        • Sub-Investigator:
          • Philippe BOIRON, MD
        • Sub-Investigator:
          • Frédéric ROCHE, MD PhD
        • Contact:
          • David HUPIN, MD
        • Contact:
          • Frédéric ROCHE, MD PhD

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:

  • Patient over 18 years old
  • Signature of informed consent
  • Confirmed diagnosis of fibromyalgia or long Covid (ACR 2016 criteria and persistent symptoms lasting more than 6 months after a positive RT-PCR test, respectively)
  • Persistent fatigue after an exercise rehabilitation program (FSS score > 36)
  • Physical inactivity, i.e. <150 minutes per week of physical activity

Exclusion Criteria:

  • Pre-existing atrial fibrillation,
  • Left ventricular ejection fraction <40%
  • Severe heart failure
  • Recent stroke or myocardial infarction (<6 months)
  • Unilateral or bilateral vagotomy
  • Pregnancy or breastfeeding

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: Other
  • 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: Patients with active tVNS
Patients consulting on St Etienne hospital and suffering from fibromyalgia and long Covid will be included.
Other: APA program
An APA program of 12 weeks, 2 sessions of 1h/week for mixed endurance, strengthening and stretching work. The program can be realized at home or in structure.
Other: Active transcutaneous VNS
After each APA session, a 1h-tVNS session is delivered on the conchae aurea of the left ear, in resting condition. Parameters of tVNS : frequency 20Hz, impulsion 200ms, amplitude 1mA below the unpleasant sensation level.
Sham Comparator: Patients with sham tVNS
Patients consulting on St Etienne hospital and suffering from fibromyalgia and long Covid will be included.
Other: APA program
An APA program of 12 weeks, 2 sessions of 1h/week for mixed endurance, strengthening and stretching work. The program can be realized at home or in structure.
Other: Sham transcutaneous VNS
After each APA session, a 1h-tVNS session is delivered on the left earlobe, in resting condition. Parameters of tVNS : frequency 20Hz, impulsion 200ms, amplitude 1mA below the unpleasant sensation level.

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
Fatigue evaluation assessed by autonomic nervous system activity
Time Frame: Month : 0; 3
The root mean square of successive differences in heart rate (in milliseconds) will be measured from a nocturnal Holter ECG recording (Novacor, Paris, France) at the end of the 3-month APA and tVNS programme (month 3) and compared with pre-programme values (inclusion).
Month : 0; 3

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
6-minute walk test (6MWT)
Time Frame: Month : 0; 6
Physical condition assessed by the walking distance covered in the 6MWT, walking distance in m.
Month : 0; 6
Adult Physical Activity Questionnaire (APAQ)
Time Frame: Month : 0; 6
Physical activity assessed by the APAQ, time spend to physical activity in hours/day.
Month : 0; 6
Step count per day
Time Frame: Month : 0; 6
Objective physical activity assessed by step count per day using a Garmin Vivofit 4 activity tracker.
Month : 0; 6
Ratio of Low Frequency to High Frequency (LF/HF)
Time Frame: Month : 0; 6
The autonomic balance (sympathetic/parasympathetic) will be analysed by measuring the LF/HF ratio on the basis of a nocturnal Holter ECG recording (Novacor, Paris, France).
Month : 0; 6
Fatigue Severity Scale (FSS)
Time Frame: Month : 0; 6
Subjective fatigue assessed by FSS, score from 9 to 63. The higher the score, the more severe the fatigue is and the more it affects the person's activities.
Month : 0; 6
Medical Outcome Study Short Form questionnaire (MOS-SF 12)
Time Frame: Month : 0; 6
Quality of life assessed by the MOS-SF 12 questionnaire , score from 0 to 100. A low score reflects a perception of poor health, loss of function and the presence of pain. A high score reflects a perception of good health, absence of functional deficit and pain.
Month : 0; 6
Pittsburgh questionnaire
Time Frame: Month : 0; 6
Quality of sleep assessed by Pittsburgh questionnaire (score 0 to 21). The 7 components of the score add up to give an overall score ranging from give an overall score ranging from 0 to 21 points, with 0 meaning that there are no difficulties, and 21 indicating major difficulties.
Month : 0; 6

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.
Centre Hospitalier Universitaire de Saint Etienne

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: David HUPIN, MD, Centre Hospitalier Universitaire de Saint Etienne

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.
October 3, 2024

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.
February 1, 2028

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.
August 1, 2028

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).
December 6, 2023

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.
December 13, 2023

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.
December 14, 2023

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.
May 6, 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.
May 5, 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.
May 1, 2026

More Information

Terms related to this study

Keywords

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.
  • 23CH153
  • 2023-A01792-43 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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