Long COVIDNCT06585254
tVNS in Long COVID-19
A study testing Transcutaneous vagus nerve stimulator in people with Long COVID and Chronic Fatigue Syndrome, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
A prior open label study has shown that transcutaneous vagus nerve stimulation [tVNS] can improve the health of some patients with postacute sequelae of SARS-CoV-2 infection (PASC), severely affected enough to also fulfill criteria for myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Long COVID, Chronic Fatigue Syndrome
- What is being tested?
- Transcutaneous vagus nerve stimulator
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2024to 1 Feb 2027
- 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 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have had documented Covid infection and then fulfill 2015 case definition for ME/CFS
- Chalder Fatigue Scale score of 4 or greater
- SF-36 Physical Function scale score ≤70
- VAS values of 3 or higher from 0 [none] 3 [substantial] to 5 [very severe burden] on at least two of the following symptoms - fatigue; widespread pain, brain fog, post-exertional malaise
Who cannot join
- BMI ≥30
- Hospitalized for COVID-19 infection
- BMI ≥30
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Use of Transcutaneous Vagus Nerve Stimulation in Reducing the Symptoms of Long COVID Patients Who Fulfill Diagnostic Criteria for ME/CFS
A prior open label study has shown that transcutaneous vagus nerve stimulation [tVNS] can improve the health of some patients with postacute sequelae of SARS-CoV-2 infection (PASC), severely affected enough to also fulfill criteria for myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). The purpose of this study is to compare two sets of stimulus parameters to determine the one that best improves the health-related quality of life of these patients over a period of 6-weeks. Patients using their assigned device for at least 30 of the 42 possible opportunities will receive the best device for an additional 6-week period.
Read the detailed description
While the US has officially said the SARS CoV-2 emergency is over, the country is left with a residual of patients who continue to experience Post-Acute Sequelae of SARS CoV-2 infection -- PASC. Unfortunately, despite a major effort to understand PASC via the NIH Researching Covid to Enhance Recovery program, no specific treatment has emerged and only a limited number of new trials has been initiated. The purpose of this proposal is to perform a clinical trial of noninvasive, transcutaneous vagus nerve stimulation [tVNS] in an attempt to find the best tVNS treatment for these patients.
The need for the proposed trial is supported by an earlier open label tVNS trial in 15 PASC patients who also fulfilled the 1994 case criteria for myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS but for simplicity CFS]. The research team chose patients with PASC-CFS for two reasons: first, CFS following Covid infection is probably the most common subgroup of patients with PASC. In the study, of 41 PASC patients whose continued symptoms over time lead to their being referred for cardiopulmonary exercise tests, 47% fulfilled the 1994 case criteria for the diagnosis of CFS. Second, the research team limited the tVNS pilot to PASC-CFS to reduce the heterogeneity inherent in the diagnosis of PASC. The research team specifically recruited non-hospitalized patients with documented Covid who remained ill with fatigue, widespread pain, cognitive complaints, and post-exertional malaise for at least 6 months after the acute infection, thus fulfilling the 1994 case criteria for CFS. Importantly, the entire study was done remotely without requiring participants to come into the medical center or stop current medical treatments.
The research team proposes to extend this study to inform us which of two possible ways of stimulating the vagus is the most effective in improving the health of PASC-CFS patients. The study again will be done remotely with the study team having access to large databases of non-hospitalized PASC sufferers. After determination that a patient had Covid, continued ill with PASC and now fulfills criteria for the diagnosis of CFS, the participant will be asked to respond to questionnaires via RedCap as to magnitude of fatigue, cognitive dysfunction, widespread pain and/or post-exertional malaise, as well as their functional status. Each will then be randomized into Treatment A or B and sent the device for these two treatment limbs with instructions to use the device for 35 min a day in the morning over a 6-week period.
During the fifth week of study participation, participants will receive a stick-on device [as well as instructions via zoom] to allow them to use the device to provide data on heart rate variability - an objective measure of treatment success. Participants will do this for a 6-minute period in the afternoon and then return the device to the study team.
Participants will complete questionnaires on RedCap at the end of the first 6-week phase and return the device to the study team to determine usage. Participants will be told they must use their device for at least 30 of the 42 days in order to get access to the device that gave the best clinical outcome for an additional 6-weeks. At the end of this second 6-week period, participants will again complete questionnaires and return their device to the study team.
- Conditions
- Long COVID, Chronic Fatigue Syndrome
- Being tested
- Transcutaneous vagus nerve stimulator
- Keywords
- Medically unexplained illness, Vagus Nerve
- Medical subject headings
- Post-Acute COVID-19 Syndrome, Fatigue Syndrome, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous vagus nerve stimulatorDevice
A device attached to the tragus of the ear which when activated stimulates an ascending branch of the vagus nerve
| Study group | Role | What they receive |
|---|---|---|
| #1: Patient controlled | Experimental | Patient will ramp up current intensity until uncomfortable, then ratchet back to what is comfortable and press button. Patient is to do this daily for 35 minutes for 6 weeks. Receives: Device: Transcutaneous vagus nerve stimulator |
| #2: Device Controlled | Experimental | Patients will ramp up current intensity until uncomfortable, then ratchet back to what is comfortable and press button. The device has software embedded in it that is used to arrive at a personalized way of stimulating the vagus nerve. At this level, the device stimulus will not be sensed by the patient. Patient is to do this daily for 35 minutes for 6 weeks. Receives: Device: Transcutaneous vagus nerve stimulator |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Chalder Fatigue Questionnaire (CFQ)
The Chalder Fatigue Questionnaire (CFQ) is used as a measure of fatigue. The CFQ consists of 11 items and uses likert scoring 0, 1, 2, 3, providing a full scale range of 0-33, where lowest score is least fatigue.
Measured: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
Change in Short Form Health Survey (SF-36)
The SF-36 is a multi-purpose, short form health survey consisting of 36 questions. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. SF-36 will be assessed for physical function score improved from baseline by 0.6 SD or 14%.
Measured: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
Visual Analog Scale (VAS) measuring Fatigue
VAS total scale from 0-5 scoring system [0 none; 1 mild; 2 moderate; 3 substantial; 4 severe; 5 very severe]. Higher score indicates poorer health outcome.
Measured: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
VAS to measure Widespread Pain
VAS total scale from 0-5 scoring system [0 none; 1 mild; 2 moderate; 3 substantial; 4 severe; 5 very severe]. Higher score indicates poorer health outcome.
Measured: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
VAS measuring Postexertional malaise (PEM)
VAS total scale from 0-5 scoring system [0 none; 1 mild; 2 moderate; 3 substantial; 4 severe; 5 very severe]. Higher score indicates poorer health outcome.
Measured: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
VAS measuring brain fog
VAS total scale from 0-5 scoring system [0 none; 1 mild; 2 moderate; 3 substantial; 4 severe; 5 very severe]. Higher score indicates poorer health outcome.
Measured: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
Global Clinical Assessment of Change
Global Clinical Assessment of Change --+3 or +2 on a scale ranging from +3 [very much improved] thru 0 [no change] to -3 [very much worse]
Measured: At 6 week (end of blinded phase) and at 12 weeks (end of open label phase)
Secondary outcomes (1)
Heart Rate Variability (HRV)
Participants will attach a device invented by the co-investigator which detects ECG and can quantify R-R intervals compute root mean square of successive differences (RMSSD) between normal heartbeats. The RMSSD reflects the beat-to-beat variance in heart rate and is the primary time-domain measure used to estimate the vagally mediated changes reflected in heart rate (HR).
Measured: Baseline and at 5-6 week (end of blinded phase)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2024
- Study start1 Nov 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion1 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long COVIDStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- 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
- Parallel groups
- Model description
- Randomized 6-week trial of two stimulus parameters in improving the health of PASC patients with CFS. Based on participation, then an additional 6 weeks using the device that had the best outcome in improving the health of PASC patients with CFS.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Benjamin Natelson, Icahn School of Medicine at Mount Sinai
- Investigators
- Benjamin H Natelson, MD, Principal investigator, Icahn School of Medicine at Mount SinaiAnna Norweg, PhD, Study director, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06585254
- Sponsor's protocol ID
- STUDY-23-01007
- Status last verified
- Jul 2026
- First submitted
- 3 Sep 2024
- Last updated
- 3 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Transcutaneous Vagus Nerve Stimulation in Reducing the Symptoms of Long COVID Patients Who Fulfill Diagnostic Criteria for ME/CFS
- ClinicalTrials.gov ID
- NCT06585254
- Acronym / sponsor ID
- STUDY-23-01007
- Conditions
- Long COVID, Chronic Fatigue Syndrome
- Keywords
- Medically unexplained illness, Vagus Nerve
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 1 Feb 2027 (estimated)
- First posted
- 5 Sep 2024 (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.
A prior open label study has shown that transcutaneous vagus nerve stimulation [tVNS] can improve the health of some patients with postacute sequelae of SARS-CoV-2 infection (PASC), severely affected enough to also fulfill criteria for myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). The purpose of this study is to compare two sets of stimulus parameters to determine the one that best improves the health-related quality of life of these patients over a period of 6-weeks. Patients using their assigned device for at least 30 of the 42 possible opportunities will receive the best device for an additional 6-week period.
Detailed description
While the US has officially said the SARS CoV-2 emergency is over, the country is left with a residual of patients who continue to experience Post-Acute Sequelae of SARS CoV-2 infection -- PASC. Unfortunately, despite a major effort to understand PASC via the NIH Researching Covid to Enhance Recovery program, no specific treatment has emerged and only a limited number of new trials has been initiated. The purpose of this proposal is to perform a clinical trial of noninvasive, transcutaneous vagus nerve stimulation [tVNS] in an attempt to find the best tVNS treatment for these patients.
The need for the proposed trial is supported by an earlier open label tVNS trial in 15 PASC patients who also fulfilled the 1994 case criteria for myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS but for simplicity CFS]. The research team chose patients with PASC-CFS for two reasons: first, CFS following Covid infection is probably the most common subgroup of patients with PASC. In the study, of 41 PASC patients whose continued symptoms over time lead to their being referred for cardiopulmonary exercise tests, 47% fulfilled the 1994 case criteria for the diagnosis of CFS. Second, the research team limited the tVNS pilot to PASC-CFS to reduce the heterogeneity inherent in the diagnosis of PASC. The research team specifically recruited non-hospitalized patients with documented Covid who remained ill with fatigue, widespread pain, cognitive complaints, and post-exertional malaise for at least 6 months after the acute infection, thus fulfilling the 1994 case criteria for CFS. Importantly, the entire study was done remotely without requiring participants to come into the medical center or stop current medical treatments.
The research team proposes to extend this study to inform us which of two possible ways of stimulating the vagus is the most effective in improving the health of PASC-CFS patients. The study again will be done remotely with the study team having access to large databases of non-hospitalized PASC sufferers. After determination that a patient had Covid, continued ill with PASC and now fulfills criteria for the diagnosis of CFS, the participant will be asked to respond to questionnaires via RedCap as to magnitude of fatigue, cognitive dysfunction, widespread pain and/or post-exertional malaise, as well as their functional status. Each will then be randomized into Treatment A or B and sent the device for these two treatment limbs with instructions to use the device for 35 min a day in the morning over a 6-week period.
During the fifth week of study participation, participants will receive a stick-on device [as well as instructions via zoom] to allow them to use the device to provide data on heart rate variability - an objective measure of treatment success. Participants will do this for a 6-minute period in the afternoon and then return the device to the study team.
Participants will complete questionnaires on RedCap at the end of the first 6-week phase and return the device to the study team to determine usage. Participants will be told they must use their device for at least 30 of the 42 days in order to get access to the device that gave the best clinical outcome for an additional 6-weeks. At the end of this second 6-week period, participants will again complete questionnaires and return their device to the study team.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized 6-week trial of two stimulus parameters in improving the health of PASC patients with CFS. Based on participation, then an additional 6 weeks using the device that had the best outcome in improving the health of PASC patients with CFS.
| Arm | Type | Receives |
|---|---|---|
| #1: Patient controlled | Experimental | Device: Transcutaneous vagus nerve stimulatorPatient will ramp up current intensity until uncomfortable, then ratchet back to what is comfortable and press button. Patient is to do this daily for 35 minutes for 6 weeks. |
| #2: Device Controlled | Experimental | Device: Transcutaneous vagus nerve stimulatorPatients will ramp up current intensity until uncomfortable, then ratchet back to what is comfortable and press button. The device has software embedded in it that is used to arrive at a personalized way of stimulating the vagus nerve. At this level, the device stimulus will not be sensed by the patient. Patient is to do this daily for 35 minutes for 6 weeks. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Must have had documented Covid infection and then fulfill 2015 case definition for ME/CFS
- Chalder Fatigue Scale score of 4 or greater
- SF-36 Physical Function scale score ≤70
- VAS values of 3 or higher from 0 [none] 3 [substantial] to 5 [very severe burden] on at least two of the following symptoms - fatigue; widespread pain, brain fog, post-exertional malaise
Key exclusion criteria (4 listed)
- BMI ≥30
- Hospitalized for COVID-19 infection
- BMI ≥30
- Pregnancy
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 stimulatorA device attached to the tragus of the ear which when activated stimulates an ascending branch of the vagus nerve | Device | #1: Patient controlled, #2: Device Controlled |
Primary outcome
The Chalder Fatigue Questionnaire (CFQ)
Time frame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
The Chalder Fatigue Questionnaire (CFQ) is used as a measure of fatigue. The CFQ consists of 11 items and uses likert scoring 0, 1, 2, 3, providing a full scale range of 0-33, where lowest score is least fatigue.
Change in Short Form Health Survey (SF-36)
Time frame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
The SF-36 is a multi-purpose, short form health survey consisting of 36 questions. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. SF-36 will be assessed for physical function score improved from baseline by 0.6 SD or 14%.
Visual Analog Scale (VAS) measuring Fatigue
Time frame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
VAS total scale from 0-5 scoring system [0 none; 1 mild; 2 moderate; 3 substantial; 4 severe; 5 very severe]. Higher score indicates poorer health outcome.
VAS to measure Widespread Pain
Time frame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
VAS total scale from 0-5 scoring system [0 none; 1 mild; 2 moderate; 3 substantial; 4 severe; 5 very severe]. Higher score indicates poorer health outcome.
VAS measuring Postexertional malaise (PEM)
Time frame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
VAS total scale from 0-5 scoring system [0 none; 1 mild; 2 moderate; 3 substantial; 4 severe; 5 very severe]. Higher score indicates poorer health outcome.
VAS measuring brain fog
Time frame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
VAS total scale from 0-5 scoring system [0 none; 1 mild; 2 moderate; 3 substantial; 4 severe; 5 very severe]. Higher score indicates poorer health outcome.
Global Clinical Assessment of Change
Time frame: At 6 week (end of blinded phase) and at 12 weeks (end of open label phase)
Global Clinical Assessment of Change --+3 or +2 on a scale ranging from +3 [very much improved] thru 0 [no change] to -3 [very much worse]
1 secondary outcome
Heart Rate Variability (HRV)
Time frame: Baseline and at 5-6 week (end of blinded phase)
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 3 Aug 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
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Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study
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Not yet recruitingPhase 3
The Study of Brave-LC LDN Treatment Trial
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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.
Benjamin H Natelson, MD principal investigator
Icahn School of Medicine at Mount Sinai
Anna Norweg, PhD study director
Icahn School of Medicine at Mount Sinai
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 stimulator in people with Long COVID and Chronic Fatigue Syndrome, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
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 4 inclusion and 4 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 3 Aug 2026. 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 United States. 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. 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?
The Chalder Fatigue Questionnaire (CFQ) (time frame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)). The study lists 7 primary outcomes in all. 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 3 Aug 2026.