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

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: Not yet recruiting
• Conditions: Chronic Fatigue Syndrome
• Intervention / Treatment: Other: APA program; Other: Active transcutaneous VNS; Other: Sham transcutaneous VNS

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David HUPIN, MD; Phone Number: +33 (0)4 77 82 84 13; Email: david.hupin@chu-st-etienne.fr
• Study Contact Backup: Name: Hélène RAINGARD, CRA; Phone Number: +33 (0)4 77 12 08 26; Email: helene.raingard@chu-st-etienne.fr

Study Locations

• France
  • Saint-Etienne, France, 42055
    • 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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Fatigue evaluation assessed by autonomic nervous system activity	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

Outcome Measure	Measure Description	Time Frame
6-minute walk test (6MWT)	Physical condition assessed by the walking distance covered in the 6MWT, walking distance in m.	Month : 0; 6
Adult Physical Activity Questionnaire (APAQ)	Physical activity assessed by the APAQ, time spend to physical activity in hours/day.	Month : 0; 6
Step count per day	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)	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)	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)	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	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

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: David HUPIN, MD, CHU Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: December 13, 2023
• First Posted (Actual): December 14, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Chronic fatigue; Transcutaneous vagal nerve stimulation (tVNS); adapted physical activity (APA)
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Disease Attributes; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Encephalomyelitis; Chronic Disease; Neuroinflammatory Diseases; Fatigue; Fatigue Syndrome, Chronic
• Other Study ID Numbers: 23CH153

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