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

NCT06968104 | Active Not Recruiting

• 1 other identifier: ERP 25-024 STIMPACT
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Post-COVID / Long-COVID; ME/CFS

Keywords

Post-COVID Syndrome; ME/CFS; Fatigue; Autonomic Dysfunction; taVNS; crossover; sham condition

Outcome Measures

Primary Outcomes (1)

• 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.

  From baseline to end of treatment at 4 weeks.

Secondary Outcomes (8)

• Patient Health (Quality of life)

  From baseline to end of treatment at 4 weeks.

• Patient Health (Ability)

  From baseline to end of treatment at 4 weeks.

• Post-Exertional Malaise (PEM)

  From baseline to end of treatment at 4 weeks.

• Autonomic Function

  From baseline to end of treatment at 4 weeks.

• Sleep Quality

  From baseline to end of treatment at 4 weeks.

Study Arms (2)

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.

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.

Device: transcutaneous vagus nerve stimulation

Interventions

transcutaneous vagus nerve stimulation 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.

Also known as: vagus stimulation, tVNS, taVNS

Intervention A

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Luxembourg: lead

Study Sites (1)

University of Luxembourg

Esch-sur-Alzette, L-4366, Luxembourg

Location

MeSH Terms

Conditions

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

Interventions

Vagus Nerve Stimulation

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; Signs and Symptoms; Autonomic Nervous System Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Officials

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

  University of Luxembourg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This is a single-blind study. Participants are blinded to the nature of the two interventions, which are referred to as Intervention A and Intervention B. One intervention delivers active transcutaneous auricular vagus nerve stimulation (taVNS) to the cymba conchae, while the other applies stimulation to the earlobe-a site without vagal innervation-serving as a sham control. To reduce placebo and expectation effects, the sham condition is not labeled or described as such to participants. Both interventions are matched for appearance and sensation to maintain effective blinding.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 5, 2025
• First Posted: May 13, 2025
• Study Start: July 18, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: August 8, 2025

Record last verified: 2025-07

Locations

LU (1)