Vagus Nerve Stimulation to the Ear to Improve Symptoms in Post-COVID-19 and ME/CFS

NCT ID: NCT06968104

Last Updated: 2025-08-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-18
• Study Completion Date: 2026-10-31

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.

Conditions

Post-COVID / Long-COVID; ME/CFS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intervention A

Participants in this arm will receive stimulation applied to the cymba conchae of the left ear, twice daily for 30 minutes over a 4-week period. This location is known to be innervated by the auricular branch of the vagus nerve. All participants will be trained in device use and electrode placement. Adherence will be tracked via device logs and virtual check-ins.

Group Type: EXPERIMENTAL

transcutaneous vagus nerve stimulation

Intervention Type: DEVICE

Transcutaneous auricular vagus nerve stimulation (taVNS) delivered using the CE-certified tVNS® device (tVNS Technologies GmbH). Stimulation parameters include a pulse width of 250-500 μs, frequency of 10-25 Hz, and an individually titrated intensity (typically up to 5 mA). The device operates with a 20-50% duty cycle and is used at home.

Intervention B

Participants in this arm will receive stimulation applied to the earlobe, a site not innervated by the vagus nerve, under the same schedule: twice daily for 30 minutes over a 4-week period. The procedure, device appearance, and instructions are identical to the active condition to maintain participant blinding. Adherence is tracked identically.

Group Type: SHAM_COMPARATOR

transcutaneous vagus nerve stimulation

Intervention Type: DEVICE

Sham stimulation using the same CE-certified tVNS® device. Electrode placement is on the earlobe, which lacks vagus nerve innervation. Stimulation parameters (pulse width, frequency, intensity, duty cycle) mirror those of the active condition, with intensity adjusted to perceptual threshold to mimic the sensation of real stimulation and preserve blinding.

Interventions

transcutaneous vagus nerve stimulation

Transcutaneous auricular vagus nerve stimulation (taVNS) delivered using the CE-certified tVNS® device (tVNS Technologies GmbH). Stimulation parameters include a pulse width of 250-500 μs, frequency of 10-25 Hz, and an individually titrated intensity (typically up to 5 mA). The device operates with a 20-50% duty cycle and is used at home.

Intervention Type: DEVICE

transcutaneous vagus nerve stimulation

Sham stimulation using the same CE-certified tVNS® device. Electrode placement is on the earlobe, which lacks vagus nerve innervation. Stimulation parameters (pulse width, frequency, intensity, duty cycle) mirror those of the active condition, with intensity adjusted to perceptual threshold to mimic the sensation of real stimulation and preserve blinding.

Intervention Type: DEVICE

Other Intervention Names

vagus stimulation; tVNS; taVNS; taVNS; Vagus stimulation; tVNS

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Luxembourg

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

André Schulz, Prof. Dr. ; Dipl. Psych.

Role: PRINCIPAL_INVESTIGATOR

University of Luxembourg

Locations

University of Luxembourg

Esch-sur-Alzette, , Luxembourg

Countries

Luxembourg

Other Identifiers

ERP 25-024 STIMPACT

Identifier Type: -

Identifier Source: org_study_id