Clinical trial NCT06968104: Vagus Nerve Stimulation to the Ear to Improve Symptoms in Post-COVID-19 and ME/CFS
Official title: Stimulation of the Transcutaneous Auricular Vagus Nerve for Improvement of Symptoms in Patients With Post-COVID Syndrome and ME/CFS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post-COVID / Long-COVID
ME/CFS
Keywords: Post-COVID Syndrome
ME/CFS
Fatigue
Autonomic Dysfunction
taVNS
crossover
sham condition
Lead sponsor: University of Luxembourg
Sponsor class: OTHER
First posted: 2025-05-13
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This study uses a randomized, single-blind, sham-controlled crossover design. Each participant will receive both Intervention A and Intervention B in a randomized sequence. Each intervention phase lasts 4 weeks, separated by a washout period of at least 4 weeks to reduce carryover effects. Participants will serve as their own controls, improving statistical power while minimizing between-subject variability. The study is single-blind: participants will not be informed which intervention is intended to stimulate the vagus nerve. All procedures are conducted remotely, and outcomes are assessed at multiple time points via digital tools and virtual check-ins.
Primary purpose: TREATMENT

Brief summary: This study is testing whether a gentle electrical stimulation of a nerve in the ear, called the vagus nerve, can help reduce fatigue and improve symptoms in people with Post-COVID Syndrome or Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The treatment, known as transcutaneous auricular vagus nerve stimulation (taVNS), is non-invasive and can be done at home using a small device.

Participants will try two different types of stimulation, called Intervention A and Intervention B, to see which may be more effective. Each intervention lasts 4 weeks and will be separated by a break of at least 4 weeks.

Participants will use the device at home twice a day for 30 minutes. Fatigue, quality of life, sleep, and daily activity will be tracked through surveys and wearable devices. All parts of the study-including check-ins and data collection-will be done remotely.

The goal is to learn whether this type of at-home nerve stimulation can safely improve symptoms in people with Post-COVID Syndrome or ME/CFS.

Detailed description: The STIMPACT study is a single-blind, randomized, controlled crossover trial designed to evaluate the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) in alleviating fatigue and autonomic dysfunction symptoms in individuals diagnosed with Post-COVID Syndrome or Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Participants will undergo two distinct intervention phases, referred to as Intervention A and Intervention B, each lasting four weeks and separated by a washout period of at least four weeks to minimize potential carryover effects. The order of interventions will be randomized for each participant.

During each intervention phase, participants will self-administer 30-minute stimulation sessions twice daily using a portable device designed for home use. Adherence to the stimulation protocol will be monitored through device usage logs and regular virtual check-ins with the research team.

The primary outcome measure is the change in fatigue levels, assessed using validated instruments such as the Fatigue Severity Scale (FSS) and the Chalder Fatigue Questionnaire, alongside daily symptom tracking through electronic diaries. Secondary outcomes include assessments of quality of life (SF-36, Bell's Disability Scale), post-exertional malaise (DePaul Symptom Questionnaire - Post-Exertional Malaise subscale), autonomic function (heart rate variability metrics), sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth Sleepiness Scale), mood (Hospital Anxiety and Depression Scale), and physical activity levels (measured via actigraphy).

Data collection will occur at baseline, mid-intervention, post-intervention, and during a follow-up period, utilizing online surveys, virtual consultations, and data synchronization from wearable devices. Statistical analyses will employ mixed-model approaches to evaluate changes in outcome measures over time and between interventions, with subgroup analyses comparing responses between the Post-COVID Syndrome and ME/CFS cohorts.

This study aims to provide robust evidence on the potential benefits of taVNS as a non-invasive, home-based therapeutic option for managing fatigue and autonomic dysfunction in these patient populations.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Post-COVID Syndrome (persistent symptoms \> 3 months post-infection)
* Diagnosis of ME/CFS (following Canadian Consensus Criteria) Aged 18-65
* Moderate to severe fatigue (Fatigue Severity Scale ≥ 5)
* Stable medical regimen for at least 3 months
* Participants who are willing to follow the treatment protocol, and able to comply with remote monitoring.
* Sufficient proficiency in German or English language

Exclusion Criteria:

* Pacemaker or other implanted electronic or metallic devices
* Neurological or psychiatric disorders unrelated to ME/CFS or Post-COVID Syndrome
* Pregnancy or breastfeeding
* History of vagus nerve damage or significant ear injury
* Previous or ongoing use of taVNS
* Bradycardia (resting heart rate below 60 beats per minute)
* permanent jewelry at close proximity to the ear tragus;
* Known severe coronary disease or recent heart attack (within 5 years)
* Medications that may influence autonomic function, HRV, and fatigue

Primary outcomes:
measure: Fatigue
timeFrame: From baseline to end of treatment at 4 weeks.
Secondary outcomes:
measure: Patient Health (Quality of life)
timeFrame: From baseline to end of treatment at 4 weeks.
measure: Patient Health (Ability)
timeFrame: From baseline to end of treatment at 4 weeks.
measure: Post-Exertional Malaise (PEM)
timeFrame: From baseline to end of treatment at 4 weeks.
measure: Autonomic Function
timeFrame: From baseline to end of treatment at 4 weeks.
measure: Sleep Quality
timeFrame: From baseline to end of treatment at 4 weeks.
measure: Sleepiness
timeFrame: From baseline to end of treatment at 4 weeks.
measure: Depression and Anxiety
timeFrame: From baseline to end of treatment at 4 weeks.
measure: Patients Activity
timeFrame: From baseline to end of treatment at 4 weeks.
Other outcomes:
Locations:
city: Esch-sur-Alzette
country: Luxembourg
facility: University of Luxembourg
Study officials:
affiliation: University of Luxembourg
name: André Schulz, Prof. Dr. ; Dipl. Psych.
role: PRINCIPAL_INVESTIGATOR
References: