search
Back to results

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

Primary Purpose

Orthostatic Intolerance, Postural Tachycardia Syndrome, Syncope, Postural

Status
Unknown status
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Transcutaneous vagal nerve stimulation (tVNS)
Placebo
Home daily transcutaneous vagal nerve stimulation
Sponsored by
Istituto Clinico Humanitas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Orthostatic Intolerance focused on measuring Postural Orthostatic Tachycardia Syndrome, Vagal stimulation, Heart Rate

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Humanitas Research HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Transcutaneous vagal nerve stimulation (tVNS)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in Heart rate
Change of Cardiovascular autonomic profile
Change in blood pressure
Change of Cardiovascular autonomic profile
Change in respiration rate
Change of Cardiovascular autonomic profile

Full Information

First Posted
September 4, 2019
Last Updated
June 29, 2022
Sponsor
Istituto Clinico Humanitas
search

1. Study Identification

Unique Protocol Identification Number
NCT04632134
Brief Title
Long-term Effects of Transcutaneous Vagal Nerve Stimulation on Postural Orthostatic Tachycardia Syndrome (POTS)
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 10, 2019 (Actual)
Primary Completion Date
June 30, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Istituto Clinico Humanitas

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Orthostatic Intolerance, Postural Tachycardia Syndrome, Syncope, Postural, Physical Disability, Autonomic Dysfunction
Keywords
Postural Orthostatic Tachycardia Syndrome, Vagal stimulation, Heart Rate

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Transcutaneous vagal nerve stimulation (tVNS)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Transcutaneous vagal nerve stimulation (tVNS)
Other Intervention Name(s)
Transcutaneous Electrical Nerve Stimulation device (Nemos ©; Cerbomed, Germany) European Conformity (CE) marking n°0408
Intervention Description
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
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sham stimulation
Intervention Description
tVNS electrodes will be positioned in the right ear of the POTS patients without delivering stimulus (Sham)
Intervention Type
Device
Intervention Name(s)
Home daily transcutaneous vagal nerve stimulation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change of Autonomic symptoms
Description
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.
Time Frame
Change from baseline Autonomic symptoms at 14 days
Secondary Outcome Measure Information:
Title
Change in Heart rate
Description
Change of Cardiovascular autonomic profile
Time Frame
Change from baseline cardiovascular autonomic profile at 14 days
Title
Change in blood pressure
Description
Change of Cardiovascular autonomic profile
Time Frame
Change from baseline cardiovascular autonomic profile at 14 days
Title
Change in respiration rate
Description
Change of Cardiovascular autonomic profile
Time Frame
Change from baseline cardiovascular autonomic profile at 14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maura Minonzio, SD
Phone
+390282246753
Email
maura.minonzio@humanitas.it
First Name & Middle Initial & Last Name or Official Title & Degree
Franca Barbic, MD
Phone
+390282246753
Email
franca.barbic@humanitas.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raffaello Furlan, Prof
Organizational Affiliation
Humanitas Research Hospital; Humanitas University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Franca Barbic, MD
Organizational Affiliation
Humanitas Research Hospital; Humanitas University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Dana Shiffer, MD
Organizational Affiliation
Humanitas Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Humanitas Research Hospital
City
Rozzano
ZIP/Postal Code
20089Raffaello
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maura Minonzio, SD
Phone
+39 02 82246753
Email
maura.minonzio@humanitas.it
First Name & Middle Initial & Last Name & Degree
Franca Barbic, MD
Phone
+39 0282246753
Email
franca.barbic@humanitas.it
First Name & Middle Initial & Last Name & Degree
Dana Shiffer, MD
First Name & Middle Initial & Last Name & Degree
Raffaello Furlan, MD
First Name & Middle Initial & Last Name & Degree
Franca Barbic, MD
First Name & Middle Initial & Last Name & Degree
Maura Minonzio, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
23753844
Citation
Raj SR. Postural tachycardia syndrome (POTS). Circulation. 2013 Jun 11;127(23):2336-42. doi: 10.1161/CIRCULATIONAHA.112.144501. No abstract available.
Results Reference
background
PubMed Identifier
10037110
Citation
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.
Results Reference
background
PubMed Identifier
9815870
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. doi: 10.1161/01.cir.98.20.2154.
Results Reference
background
PubMed Identifier
25164906
Citation
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.
Results Reference
background
PubMed Identifier
22568773
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.
Results Reference
background
PubMed Identifier
20579544
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.
Results Reference
background
PubMed Identifier
27388046
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.
Results Reference
background
PubMed Identifier
10694528
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. doi: 10.1161/01.cir.101.8.886.
Results Reference
background
PubMed Identifier
8392653
Citation
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.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs