Clinical trial NCT05918965: Vagus Stimulation in Female Long COVID Patients.
Official title: Effects of Transcutaneous Electrical Neurostimulation on Female Patients With Long COVID - a Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Vagus Nerve Diseases
Long COVID
Long Covid19
Post-COVID-19 Syndrome
Post-COVID Syndrome
Post COVID-19 Condition
Post COVID Condition
Keywords: auricular transcutaneous electrical vagal nerve stimulation
TENS
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2023-06-26
Enrollment: 45
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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)

Eligibility criteria: 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

Primary outcomes:
measure: Heart rate variability
timeFrame: 3 times for 12 weeks
Secondary outcomes:
measure: blood pressure and pulse
timeFrame: 3 times for 12 weeks
measure: Saliva cortisol
timeFrame: 3 times for 12 weeks
measure: Questionnaire Brief Fatigue Inventory (BFI)
timeFrame: 3 times for 12 weeks
measure: Questionnaire Short form (SF)-36
timeFrame: 3 times for 12 weeks
measure: Questionnaire Borg-Scale
timeFrame: 3 times for 12 weeks
measure: Questionnaire Insomnia Severity Index (ISI)
timeFrame: 3 times for 12 weeks
measure: Post-COVID-19 Functional Status scale (PCFS)
timeFrame: 3 times for 12 weeks
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Department of Physical Medicine, Rehabilitation and Occupational Medicine, Medical University of Vienna
Study officials:
affiliation: PMR&O
name: Richard Crevenna, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Raveendran AV, Jayadevan R, Sashidharan S. Long COVID: An overview. Diabetes Metab Syndr. 2021 May-Jun;15(3):869-875. doi: 10.1016/j.dsx.2021.04.007. Epub 2021 Apr 20.
citation: Shah W, Hillman T, Playford ED, Hishmeh L. Managing the long term effects of covid-19: summary of NICE, SIGN, and RCGP rapid guideline. BMJ. 2021 Jan 22;372:n136. doi: 10.1136/bmj.n136. No abstract available.
citation: Sylvester SV, Rusu R, Chan B, Bellows M, O'Keefe C, Nicholson S. Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review. Curr Med Res Opin. 2022 Aug;38(8):1391-1399. doi: 10.1080/03007995.2022.2081454. Epub 2022 Jun 20.
citation: Dani M, Dirksen A, Taraborrelli P, Torocastro M, Panagopoulos D, Sutton R, Lim PB. Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies. Clin Med (Lond). 2021 Jan;21(1):e63-e67. doi: 10.7861/clinmed.2020-0896. Epub 2020 Nov 26.
citation: Fudim M, Qadri YJ, Ghadimi K, MacLeod DB, Molinger J, Piccini JP, Whittle J, Wischmeyer PE, Patel MR, Ulloa L. Implications for Neuromodulation Therapy to Control Inflammation and Related Organ Dysfunction in COVID-19. J Cardiovasc Transl Res. 2020 Dec;13(6):894-899. doi: 10.1007/s12265-020-10031-6. Epub 2020 May 26.