Long-term Effects of Transcutaneous Vagal Nerve Stimulation on Postural Orthostatic Tachycardia Syndrome (POTS)

NCT ID: NCT04632134

Last Updated: 2022-06-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-10

Study Completion Date

2022-12-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by symptoms of chronic orthostatic intolerance such as fatigue, lightheadedness, dizziness, palpitations and by pronounced tachycardia upon standing.

The aims of the present research study are to test whether a daily transcutaneous vagal nerve stimulation (tVNS) performed for 14 consecutive days may improve heart rate response and reduce disabling symptoms while standing.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by symptoms of chronic orthostatic intolerance such as fatigue, lightheadedness, dizziness, palpitations and by pronounced tachycardia without hypotension upon standing. In healthy volunteers, transcutaneous vagal nerve stimulation (tVNS) may result in increased cardiac vagal activity and reduced vascular sympathetic drive with minimal, if any, side effects. It is possible to hypothesize that any therapeutic intervention aimed at increasing cardiac vagal modulation might result in clinical improvement of the disease.

The aim of the study are to evaluate the medium-term effects of tVNS, performed every day for a 14 days on cardiovascular autonomic profile and symptoms intensity in POTS patients.

Study and General Design

Phase 1- Enrollment:

23 POTS patients, older than 18 years of age, will be consecutively enrolled. Each POTS patient will undergo complete medical evaluation at the time of enrollment, which will take place seven days before baseline recordings (i.e. Control day, see below), in order to individually optimize the tVNS amplitude and get patients familiarized with both the tVNS procedure and the clinical laboratory environment. On the same day, 30-minute continuous tVNS will be delivered to the patients under rigorous medical and hemodynamic supervision to exclude any kind of short term adverse effects.

Transcutaneous vagal nerve stimulation (tVNS) will be performed using a noninvasive battery powered Transcutaneous Electrical Nerve Stimulation device (Nemos ©; Cerbomed, Germany). Electrical stimulation will be delivered by external electrodes through the skin surface at the conca of right external ear. Electrical current will be applied continuously with a pulse width of 200 μs and pulse frequency of 25 Hz, differently from previous protocols. Stimulation amplitude will be adjusted between 0.1-6 milliampere (mA), to a maximal amplitude level without causing patient discomfort.

Phase 2 Sham tVNS and Effective tVNS:

In every subject continuous ECG, beat by beat non-invasive arterial pressure (Nexfin device), respiratory activity by thoracic piezoelectric belt will be recorded while supine and during 75° head-up tilt (rest-tilt protocol). After positioning the tVNS electrodes in the right ear but without delivering tVNS (Sham tVNS), above mentioned signals will be recorded for 10 minutes while supine, for 15 minutes during 75° head-up tilt. The same protocol will be repeated during stimulation amplitude will be adjusted to maximal tolerable level as assessed in Phase 1 (effective acute tVNS).

The Composite Autonomic Symptom Scale (COMPASS 31) COMPASS 31 will be used to quantify the following autonomic symptoms: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, urinary and pupillomotor dysfunction symptoms .

Phase 3-Home daily stimulation:

Thereafter, every patient will be provided with a Nemos© device and electrodes for home daily stimulation. Daily stimulation will consist of 4 hours of stimulation organized as 4 sessions each lasting 1 hour, to be applied at the patient's convenience.

Phase 4- Post- 14-day tVNS. After 14 days of home daily tVNS, all the patients will undergo the rest-tilt protocol described in Phase 2.

COMPASS 31 questionnaire will be administered while supine and during 75° head-up Tilt

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Orthostatic Intolerance Postural Tachycardia Syndrome Syncope, Postural Physical Disability Autonomic Dysfunction

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Transcutaneous vagal nerve stimulation (tVNS)

After positioning the tVNS electrodes in the right ear but without delivering tVNS (Sham tVNS), above mentioned signals will be recorded for 10 minutes while supine, for 15 minutes during 75° head-up tilt.

The same protocol will be performed during active tVNS.

The tVNS will be performed while 15 minutes in supine position and during 75°head-up Tilt.

Thereafter, every patient will be provided with a Nemos© device and electrodes for home daily stimulation. Daily stimulation will consist of 4 hours of stimulation organized as 4 sessions each lasting 1 hour, to be applied at the patient's convenience.

Group Type EXPERIMENTAL

Transcutaneous vagal nerve stimulation (tVNS)

Intervention Type DEVICE

Transcutaneous vagal nerve stimulation (tVNS) will be performed using a noninvasive battery powered Transcutaneous Electrical Nerve Stimulation device (Nemos ©; Cerbomed, Germany). Electrical stimulation will be delivered by external electrodes through the skin surface at the conca of right external ear. Electrical current will be applied continuously with a pulse width of 200 μs and pulse frequency of 25 Hz. Stimulation amplitude will be adjusted between 0.1-6 mA, to a maximal amplitude level without causing patient discomfort.

Placebo

Intervention Type OTHER

tVNS electrodes will be positioned in the right ear of the POTS patients without delivering stimulus (Sham)

Home daily transcutaneous vagal nerve stimulation

Intervention Type DEVICE

The home stimulation will consist of 4 hours of stimulation by the tVNS device organized as a 4 sessions of 1 hour. The home stimulation will last for 14 consecutive days.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Transcutaneous vagal nerve stimulation (tVNS)

Transcutaneous vagal nerve stimulation (tVNS) will be performed using a noninvasive battery powered Transcutaneous Electrical Nerve Stimulation device (Nemos ©; Cerbomed, Germany). Electrical stimulation will be delivered by external electrodes through the skin surface at the conca of right external ear. Electrical current will be applied continuously with a pulse width of 200 μs and pulse frequency of 25 Hz. Stimulation amplitude will be adjusted between 0.1-6 mA, to a maximal amplitude level without causing patient discomfort.

Intervention Type DEVICE

Placebo

tVNS electrodes will be positioned in the right ear of the POTS patients without delivering stimulus (Sham)

Intervention Type OTHER

Home daily transcutaneous vagal nerve stimulation

The home stimulation will consist of 4 hours of stimulation by the tVNS device organized as a 4 sessions of 1 hour. The home stimulation will last for 14 consecutive days.

Intervention Type DEVICE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Transcutaneous Electrical Nerve Stimulation device (Nemos ©; Cerbomed, Germany) European Conformity (CE) marking n°0408 Sham stimulation

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Clinical diagnosis of Postural Orthostatic Tachycardia Syndrome
* Older than 18 years

Exclusion Criteria

* Dysautonomias other than POTS
* Neurodegenerative diseases
* History/family history of seizures
* Atrial fibrillation and other relevant cardiac rhythm disturbances
* Chronic inflammatory diseases
* Chronic use on anti-inflammatory drugs
* Diabetes
* Other neurological or psychiatric diseases
* Pacemakers or other electronic implants inserted into the body
* Coronary disorders
* Elevated intracranial blood pressure
* Assumption of drugs facilitating seizures
* Assumption ofpsychiatric drugs
* Alcohol abuse
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Istituto Clinico Humanitas

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Raffaello Furlan, Prof

Role: STUDY_DIRECTOR

Humanitas Research Hospital; Humanitas University

Franca Barbic, MD

Role: STUDY_CHAIR

Humanitas Research Hospital; Humanitas University

Dana Shiffer, MD

Role: PRINCIPAL_INVESTIGATOR

Humanitas Research Hospital IRCCS, Rozzano-Milan

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Humanitas Research Hospital

Rozzano, , Italy

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Italy

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Maura Minonzio, SD

Role: CONTACT

+390282246753

Franca Barbic, MD

Role: CONTACT

+390282246753

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Maura Minonzio, SD

Role: primary

+39 02 82246753

Franca Barbic, MD

Role: backup

+39 0282246753

References

Explore related publications, articles, or registry entries linked to this study.

Raj SR. Postural tachycardia syndrome (POTS). Circulation. 2013 Jun 11;127(23):2336-42. doi: 10.1161/CIRCULATIONAHA.112.144501. No abstract available.

Reference Type BACKGROUND
PMID: 23753844 (View on PubMed)

Robertson D. The epidemic of orthostatic tachycardia and orthostatic intolerance. Am J Med Sci. 1999 Feb;317(2):75-7. doi: 10.1097/00000441-199902000-00001. No abstract available.

Reference Type BACKGROUND
PMID: 10037110 (View on PubMed)

Furlan R, Jacob G, Snell M, Robertson D, Porta A, Harris P, Mosqueda-Garcia R. Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control. Circulation. 1998 Nov 17;98(20):2154-9. doi: 10.1161/01.cir.98.20.2154.

Reference Type BACKGROUND
PMID: 9815870 (View on PubMed)

Clancy JA, Mary DA, Witte KK, Greenwood JP, Deuchars SA, Deuchars J. Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity. Brain Stimul. 2014 Nov-Dec;7(6):871-7. doi: 10.1016/j.brs.2014.07.031. Epub 2014 Jul 16.

Reference Type BACKGROUND
PMID: 25164906 (View on PubMed)

Napadow V, Edwards RR, Cahalan CM, Mensing G, Greenbaum S, Valovska A, Li A, Kim J, Maeda Y, Park K, Wasan AD. Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation. Pain Med. 2012 Jun;13(6):777-89. doi: 10.1111/j.1526-4637.2012.01385.x. Epub 2012 May 8.

Reference Type BACKGROUND
PMID: 22568773 (View on PubMed)

Fu Q, Vangundy TB, Galbreath MM, Shibata S, Jain M, Hastings JL, Bhella PS, Levine BD. Cardiac origins of the postural orthostatic tachycardia syndrome. J Am Coll Cardiol. 2010 Jun 22;55(25):2858-68. doi: 10.1016/j.jacc.2010.02.043.

Reference Type BACKGROUND
PMID: 20579544 (View on PubMed)

Murray AR, Atkinson L, Mahadi MK, Deuchars SA, Deuchars J. The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control. Auton Neurosci. 2016 Aug;199:48-53. doi: 10.1016/j.autneu.2016.06.004. Epub 2016 Jun 28.

Reference Type BACKGROUND
PMID: 27388046 (View on PubMed)

Furlan R, Porta A, Costa F, Tank J, Baker L, Schiavi R, Robertson D, Malliani A, Mosqueda-Garcia R. Oscillatory patterns in sympathetic neural discharge and cardiovascular variables during orthostatic stimulus. Circulation. 2000 Feb 29;101(8):886-92. doi: 10.1161/01.cir.101.8.886.

Reference Type BACKGROUND
PMID: 10694528 (View on PubMed)

Low PA. Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc. 1993 Aug;68(8):748-52. doi: 10.1016/s0025-6196(12)60631-4.

Reference Type BACKGROUND
PMID: 8392653 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

111

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Vagal Stimulation in POTS
NCT03124355 ACTIVE_NOT_RECRUITING PHASE1
VNS for Long-COVID-19
NCT05630040 COMPLETED NA