Post-COVID / Long-COVIDSTIMPACTNCT06968104
Vagus Nerve Stimulation to the Ear to Improve Symptoms in Post-COVID-19 and ME/CFS
A study testing transcutaneous vagus nerve stimulation in people with Post-COVID / Long-COVID and ME/CFS, run by University of Luxembourg at 1 site in Luxembourg.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Post-COVID / Long-COVID, ME/CFS
- What is being tested?
- transcutaneous vagus nerve stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteLuxembourg
- Study dates
- 18 Jul 2025to Oct 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Stimulation of the Transcutaneous Auricular Vagus Nerve for Improvement of Symptoms in Patients With Post-COVID Syndrome and ME/CFS
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.
Read more
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.
Read the 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
- Being tested
- transcutaneous vagus nerve stimulation
- Keywords
- Post-COVID Syndrome, ME/CFS, Fatigue, Autonomic Dysfunction, taVNS, crossover, sham condition
- Medical subject headings
- Post-Acute COVID-19 Syndrome, Fatigue Syndrome, Chronic, Fatigue, Primary Dysautonomias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcutaneous vagus nerve stimulationDevice
Also called vagus stimulation, tVNS, taVNS
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.
transcutaneous vagus nerve stimulationDevice
Also called taVNS, Vagus stimulation, tVNS
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention A | Experimental | 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. Receives: Device: transcutaneous vagus nerve stimulation |
| Intervention B | Sham comparator | 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. Receives: Device: transcutaneous vagus nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue
Reduction in fatigue measured by the Fatigue Severity and Chalder Fatigue Scales. The FSS is a 9-item scale that measures the severity of fatigue and how much it affects the person's activities and lifestyle in patients with a variety of disorders. The items are scored on a 7 point scale with 1=strongly disagree and 7=strongly agree. The minimum score=9 and maximum score possible=63. Higher the score=greater fatigue severity. More common way of scoring: mean of all the scores with minimum score being 1 and maximum score being 7. The Chalder Fatigue Scale consists of 11 items scored on a 4-point Likert scale (0 to 3). Higher total scores reflect a greater degree of fatigue.
Measured: From baseline to end of treatment at 4 weeks.
Secondary outcomes (8)
Patient Health (Quality of life)
Improvements in quality of life, assessed by the Short Form Health Survey (SF-36). The SF-36 is a 36-item scale constructed to survey health status and quality of life (Ware \& Sherbourne, 1992). Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Greater scores indicate greater functioning.
Measured: From baseline to end of treatment at 4 weeks.
Patient Health (Ability)
Assessment of functional ability/disability using the Bell CFIDS disability scale (Bell Score). Scores from 0 to 100, lower score indicating greater disability.
Measured: From baseline to end of treatment at 4 weeks.
Post-Exertional Malaise (PEM)
PEM measured by the DePaul Symptom Questionnaire - Post-Exertional-Malaise Subscale (DSQ-PEM)
Measured: From baseline to end of treatment at 4 weeks.
Autonomic Function
Autonomic function evaluated through Heart Rate Variability (HRV)
Measured: From baseline to end of treatment at 4 weeks.
Sleep Quality
Assessed by the Pittsburgh Sleep Quality Index (PSQI) and daily E-Diary entries.
Measured: From baseline to end of treatment at 4 weeks.
Sleepiness
Measured by the Epworth Sleepiness Scale (ESS). Scores from 0 to 24:
0-5 lower normal daytime sleepiness 6-10 normal daytime sleepiness 11-12 mild daytime symptoms 13-15 moderate daytime symptoms 16-24 severe daytime symptoms
Measured: From baseline to end of treatment at 4 weeks.
Depression and Anxiety
Evaluated using the Hospital Anxiety and Depression Scale (HADS). The HADS consists of 14 questions that can be scored from 0 to 3. Seven questions relate to anxiety (indicated by an 'A') and 7 questions relate to depression (as shown by a 'D'). 0-7 = Normal; 8-10 = Borderline abnormal (borderline case); 11-21 = Abnormal (case).
Measured: From baseline to end of treatment at 4 weeks.
Patients Activity
monitored through actigraphy (i.e. step count)
Measured: From baseline to end of treatment at 4 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2025
- Study start18 Jul 2025
- Primary completionOct 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-COVID / Long-COVIDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Luxembourg
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- André Schulz, Prof. Dr. ; Dipl. Psych., Principal investigator, University of Luxembourg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06968104
- Sponsor's protocol ID
- ERP 25-024 STIMPACT
- Acronym
- STIMPACT
- Status last verified
- Jul 2025
- First submitted
- 5 May 2025
- Last updated
- 8 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stimulation of the Transcutaneous Auricular Vagus Nerve for Improvement of Symptoms in Patients With Post-COVID Syndrome and ME/CFS
- ClinicalTrials.gov ID
- NCT06968104
- Acronym / sponsor ID
- STIMPACT / ERP 25-024 STIMPACT
- Conditions
- Post-COVID / Long-COVID, ME/CFS
- Keywords
- Post-COVID Syndrome, ME/CFS, Fatigue, Autonomic Dysfunction, taVNS, crossover, sham condition
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- University of LuxembourgUniversity, hospital or other
- Study start
- 18 Jul 2025 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 13 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Intervention A | Experimental | Device: transcutaneous vagus nerve stimulationParticipants 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. |
| Intervention B | Sham comparator | Device: transcutaneous vagus nerve stimulationParticipants 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| transcutaneous vagus nerve stimulationAlso: vagus stimulation, tVNS, taVNSTranscutaneous 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. | Device | Intervention A |
| transcutaneous vagus nerve stimulationAlso: taVNS, Vagus stimulation, tVNSSham 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. | Device | Intervention B |
Primary outcome
Fatigue
Time frame: From baseline to end of treatment at 4 weeks.
Reduction in fatigue measured by the Fatigue Severity and Chalder Fatigue Scales. The FSS is a 9-item scale that measures the severity of fatigue and how much it affects the person's activities and lifestyle in patients with a variety of disorders. The items are scored on a 7 point scale with 1=strongly disagree and 7=strongly agree. The minimum score=9 and maximum score possible=63. Higher the score=greater fatigue severity. More common way of scoring: mean of all the scores with minimum score being 1 and maximum score being 7. The Chalder Fatigue Scale consists of 11 items scored on a 4-point Likert scale (0 to 3). Higher total scores reflect a greater degree of fatigue.
8 secondary outcomes
Patient Health (Quality of life)
Time frame: From baseline to end of treatment at 4 weeks.
Patient Health (Ability)
Time frame: From baseline to end of treatment at 4 weeks.
Post-Exertional Malaise (PEM)
Time frame: From baseline to end of treatment at 4 weeks.
Autonomic Function
Time frame: From baseline to end of treatment at 4 weeks.
Sleep Quality
Time frame: From baseline to end of treatment at 4 weeks.
Sleepiness
Time frame: From baseline to end of treatment at 4 weeks.
Depression and Anxiety
Time frame: From baseline to end of treatment at 4 weeks.
Patients Activity
Time frame: From baseline to end of treatment at 4 weeks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2025.
- Individual participant dataSharing planned: Undecided
Related trials for Post-COVID / Long-COVID
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Recruiting
Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study
ME/CFS, Fibromyalgia (FM)
Not yet recruitingPhase 3
The Study of Brave-LC LDN Treatment Trial
Post-acute COVID-19 Syndrome
Active, not recruitingObservational study
Epigenetic Changes in Long COVID Patients
Long COVID-19 Syndrome, Long COVID Symptoms
Enrolling by invitationPhase 2
Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2
Systemic Inflammation, Neuroinflammation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
André Schulz, Prof. Dr. ; Dipl. Psych. principal investigator
University of Luxembourg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing transcutaneous vagus nerve stimulation in people with Post-COVID / Long-COVID and ME/CFS, run by University of Luxembourg at 1 site in Luxembourg.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Luxembourg. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fatigue (time frame: From baseline to end of treatment at 4 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2025.