tVNS in Long COVID-19

NCT06585254 | Recruiting FDA Device

• 1 other identifier: STUDY-23-01007
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Long COVID; Chronic Fatigue Syndrome

Keywords

Medically unexplained illness; Vagus Nerve

Outcome Measures

Primary Outcomes (7)

• 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.

  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%.

  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.

  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.

  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.

  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.

  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 \[very much worse\]

  At 6 week (end of blinded phase) and at 12 weeks (end of open label phase)

Secondary Outcomes (1)

• Heart Rate Variability (HRV)

  Baseline and at 5-6 week (end of blinded phase)

Study Arms (2)

#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.

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.

Device: Transcutaneous vagus nerve stimulator

Interventions

Transcutaneous vagus nerve stimulator DEVICE

A device attached to the tragus of the ear which when activated stimulates an ascending branch of the vagus nerve

#1: Patient controlled; #2: Device Controlled

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Fatigue Syndrome, Chronic

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases

Study Officials

• Benjamin H Natelson, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Anna Norweg, PhD

  Icahn School of Medicine at Mount Sinai

  STUDY DIRECTOR

Central Study Contacts

Patrick Quan

CONTACT

212-844-6665; Patrick.quan@mssm.edu

Anna Norweg, PhD

CONTACT

212-844-6665; anna.norweg@mssm.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: A computer-generated randomization list will be used to assign subjects into Treatment A or Treatment B. Study team members doing outcome assessments will be blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: 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.

Study Record Dates

• First Submitted: September 3, 2024
• First Posted: September 5, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee (\'learned intermediary\') identified for this purpose. To achieve aims in the approved proposal. Proposals should be directed to anna.norweg@mssm.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)