Clinical trial NCT06585254: tVNS in Long COVID-19
Official title: Use of Transcutaneous Vagus Nerve Stimulation in Reducing the Symptoms of Long COVID Patients Who Fulfill Diagnostic Criteria for ME/CFS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Long COVID
Chronic Fatigue Syndrome
Keywords: Medically unexplained illness
Vagus Nerve
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2024-09-05
Enrollment: 50
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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). 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* BMI ≥30
* Hospitalized for COVID-19 infection
* BMI ≥30
* Pregnancy

Primary outcomes:
measure: The Chalder Fatigue Questionnaire (CFQ)
timeFrame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
measure: Change in Short Form Health Survey (SF-36)
timeFrame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
measure: Visual Analog Scale (VAS) measuring Fatigue
timeFrame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
measure: VAS to measure Widespread Pain
timeFrame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
measure: VAS measuring Postexertional malaise (PEM)
timeFrame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
measure: VAS measuring brain fog
timeFrame: Baseline, at 6 week (end of blinded phase), and at 12 weeks (end of open label phase)
measure: Global Clinical Assessment of Change
timeFrame: At 6 week (end of blinded phase) and at 12 weeks (end of open label phase)
Secondary outcomes:
measure: Heart Rate Variability (HRV)
timeFrame: Baseline and at 5-6 week (end of blinded phase)
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Benjamin H Natelson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Anna Norweg, PhD
role: STUDY_DIRECTOR
References: