Vagus Stimulation in Female Long COVID Patients.

Study Overview
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Brief Summary
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The aim of the present pilot study is to investigate the acceptance, feasibility and implementation of the vagus nerv stimulation in Long COVID patients. Additionally, the effects on parameters of the autonomic nervous system as well as on symptoms of Long COVID will be described in a pre/post comparison. For this purpose, a total of 45 female Long COVID patients will participate in the randomized controlled pilot study. Patients will perform auricular vagus stimulation daily for 12 weeks. The patient collective will be randomized into three groups (A: 10 hertz, B: 25 hertz, C: 2 hertz=control group). If appropriate results are obtained, further adequately powered intervention studies are planned.

Detailed Description
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Patients start on day 0, when the first assessment takes place. This consists of a medical diagnostic interview and sociodemographic, anthropometric, medical and functional data are collected (for a detailed description, see chapter 5. Statistics). Subsequently, the patients fill out the given questionnaires (paper/pencil version), which are then evaluated. Subsequently, the test persons are trained by a doctor how the electrical stimulation works with a demo device. Finally, the device is taken over by the company Schwa-Medico. The whole first assessment lasts about 2 hours and always takes place from 8 a.m. at constant room temperature (22-23 C°). The outcome parameters are recorded before the start of the vagus nerve stimulation (T0), during the treatment after 4 weeks (T0+4Wo) and after a total of 12 weeks (T0+12Wo) after the end of the therapy. Which assessments are collected at the different time points is listed in the biometry section. The assessments are performed by physicians of the Department of Physical Medicine, Rehabilitation and Occupational Medicine. All assessments take place at relatively the same time, at constant room temperature (22-23 C°). The patients have to appear fasting. T0: Medical history, examination, randomization, pre-tests, enrollment. T0+4Wo: Intermediate examination T0+12Wo: final examination, post-tests, return of device This pilot study investigates the acceptability, feasibility, and implementation of the VNS measure in Long COVID patients. In addition, effects on autonomic nervous system parameters (heart rate, blood pressure, rate pressure product, heart rate variability = HRV, cortisol in saliva), on symptoms fatigue, dyspnea as well as health-related quality of life (HRQOL) are described: Time points: T0, T0+4wk, T0+12wk. Parameters - collected at relatively the same time each day, at constant room temperature (22-23 C°): Documentation of blood pressure and pulse rate: by means of Boso Medicus (Bosch + Sohn GmbH u. Co. KG, Jungingen, Germany), calculation of the so-called rate pressure-product (syst. blood pressure x heart rate) Heart rate variability Salivary cortisol Fatigue: Brief Fatigue Inventory (BFI) Health-related quality of life (HRQOL): SF-36 (short form) questionnaire instrument Dyspnea: Modified Borg Scale Sleep: Insomnia Severity Index (ISI)

Official Title
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Effects of Transcutaneous Electrical Neurostimulation on Female Patients With Long COVID - a Pilot Study

Conditions
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Vagus Nerve Diseases, Long COVID, Long Covid19, Post-COVID-19 Syndrome, Post-COVID Syndrome, Post COVID-19 Condition, Post COVID Condition

Intervention / Treatment
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* Device: transcutaneous electrical vagal neurostimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients with Long COVID (history, physical examination, findings) age 18-70 years signed informed consent Exclusion Criteria: Hearing aid implants (cochlear implants) surgical transection of the vagus nerve Malignancies autoimmune diseases orthopedic diseases rheumatological diseases neurological diseases postoperative, fresh injuries to the ear febrile diseases inflammations psychiatric diseases pacemakers implanted cardioverter and defibrillators (ICDs) seizure disorders Meniere's disease negative experience with electrotherapy insufficient knowledge of the German language

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vagus Nerve Stimulation with 10 Hertz<br>Twelve weeks home therapy with transcutaneous electrical neurostimulation (TENSeco®, CE197, Schwa-Medico Gmbh), transcutaneous 2-channel nerve stimulator. Matching ear electrode 3 DTS. Stimulation frequency: 10 Hertz Intensity: sensitive threshold; clearly perceptible, but pleasant Form of stimulation: biphasic Duration: 30 min Position: left ear Frequency: daily, in the evening, when all daily activities are done | Device: transcutaneous electrical vagal neurostimulation<br>* daily for 12 weeks<br>|
| Active Comparator: Vagus Nerve Stimulation with 25 Hertz<br>Twelve weeks home therapy with transcutaneous electrical neurostimulation (TENSeco®, CE197, Schwa-Medico Gmbh), transcutaneous 2-channel nerve stimulator. Matching ear electrode 3 DTS. Stimulation frequency: 25 Hertz Intensity: sensitive threshold; clearly perceptible, but pleasant Form of stimulation: biphasic Duration: 30 min Position: left ear Frequency: daily, in the evening, when all daily activities are done | Device: transcutaneous electrical vagal neurostimulation<br>* daily for 12 weeks<br>|
| Experimental: Vagus Nerve Stimulation with 2 Hertz<br>Twelve weeks home therapy with transcutaneous electrical neurostimulation (TENSeco®, CE197, Schwa-Medico Gmbh), transcutaneous 2-channel nerve stimulator. Matching ear electrode 3 DTS. Stimulation frequency: 2 Hertz Intensity: sensitive threshold; clearly perceptible, but pleasant Form of stimulation: biphasic Duration: 30 min Position: left ear Frequency: daily, in the evening, when all daily activities are done | Device: transcutaneous electrical vagal neurostimulation<br>* daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate variability | 20-minute documentation of the heart rate variability with a 24-hour-elektrocardiography | 3 times for 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood pressure and pulse | via Boso Medicus plus their mutiplication for the rate-pressure-product | 3 times for 12 weeks | 
| Saliva cortisol | in the morning until the latest 10am | 3 times for 12 weeks | 
| Questionnaire Brief Fatigue Inventory (BFI) | Fatigue evaluation | 3 times for 12 weeks | 
| Questionnaire Short form (SF)-36 | Health related quality of life evaluation | 3 times for 12 weeks | 
| Questionnaire Borg-Scale | Dyspnea evaluation | 3 times for 12 weeks | 
| Questionnaire Insomnia Severity Index (ISI) | Sleep evaluation | 3 times for 12 weeks | 
| Post-COVID-19 Functional Status scale (PCFS) | Grade 0-4 | 3 times for 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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auricular transcutaneous electrical vagal nerve stimulation, TENS