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

Physical Disability Clinical Trial

— VAG-POTS  

Official title:

Long-term Effects of Transcutaneous Vagal Nerve Stimulation on Symptoms and Cardiovascular Autonomic Profile of Patients With Postural Orthostatic Tachycardia Syndrome (POTS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04632134
• Other study ID #: 111
• Status: Recruiting
• Phase: N/A
• Start date: November 10, 2019
• Est. completion date: December 30, 2022

Study information

• Verified date: June 2021
• Source: Istituto Clinico Humanitas
• Contact: Maura Minonzio, SD
• Phone: +390282246753
• Email: maura.minonzio[@]humanitas.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 23
• Est. completion date: December 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Autonomic Dysfunction
• Autonomic Nervous System Diseases
• Orthostatic Intolerance
• Physical Disability
• Postural Orthostatic Tachycardia Syndrome
• Postural Tachycardia Syndrome
• Primary Dysautonomias
• Syncope
• Syncope, Postural
• Syndrome
• Tachycardia

Intervention

Device:
• 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.

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

Device:
• 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.

Locations

Country	Name	City	State
Italy	Humanitas Research Hospital	Rozzano

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Clinico Humanitas

Country where clinical trial is conducted

Italy, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Low PA. Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc. 1993 Aug;68(8):748-52. — View Citation

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. Review. — View Citation

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. — View Citation

Raj SR. Postural tachycardia syndrome (POTS). Circulation. 2013 Jun 11;127(23):2336-42. doi: 10.1161/CIRCULATIONAHA.112.144501. Review. — View Citation

Robertson D. The epidemic of orthostatic tachycardia and orthostatic intolerance. Am J Med Sci. 1999 Feb;317(2):75-7. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of Autonomic symptoms	Autonomic symptoms will be assessed by the Composite Autonomic Symptom Scale (COMPASS 31) questionnaire. This is based on 31 items and a score ranging from 0 to100, 0 being the absence of symptom and 100 the greatest symptom intensity. The COMPASS 31 will be used to quantify the following autonomic symptoms: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, urinary and pupillomotor dysfunction symptoms.	Change from baseline Autonomic symptoms at 14 days
Secondary	Change in Heart rate	Change of Cardiovascular autonomic profile	Change from baseline cardiovascular autonomic profile at 14 days
Secondary	Change in blood pressure	Change of Cardiovascular autonomic profile	Change from baseline cardiovascular autonomic profile at 14 days
Secondary	Change in respiration rate	Change of Cardiovascular autonomic profile	Change from baseline cardiovascular autonomic profile at 14 days