NCT04632134

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
23

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Nov 2019

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 4, 2019

Completed
2 months until next milestone

Study Start

First participant enrolled

November 10, 2019

Completed
1 year until next milestone

First Posted

Study publicly available on registry

November 17, 2020

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2022

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2022

Completed
Last Updated

June 30, 2022

Status Verified

June 1, 2021

Enrollment Period

2.6 years

First QC Date

September 4, 2019

Last Update Submit

June 29, 2022

Conditions

Keywords

Postural Orthostatic Tachycardia SyndromeVagal stimulationHeart Rate

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Change in Heart rate

    Change from baseline cardiovascular autonomic profile at 14 days

  • Change in blood pressure

    Change from baseline cardiovascular autonomic profile at 14 days

  • Change in respiration rate

    Change from baseline cardiovascular autonomic profile at 14 days

Study Arms (1)

Transcutaneous vagal nerve stimulation (tVNS)

EXPERIMENTAL

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.

Device: Transcutaneous vagal nerve stimulation (tVNS)Other: PlaceboDevice: Home daily transcutaneous vagal nerve stimulation

Interventions

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.

Also known as: Transcutaneous Electrical Nerve Stimulation device (Nemos ©; Cerbomed, Germany) European Conformity (CE) marking n°0408
Transcutaneous vagal nerve stimulation (tVNS)
PlaceboOTHER

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

Also known as: Sham stimulation
Transcutaneous vagal nerve stimulation (tVNS)

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.

Transcutaneous vagal nerve stimulation (tVNS)

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Humanitas Research Hospital

Rozzano, 20089Raffaello, Italy

RECRUITING

Related Publications (9)

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

    PMID: 23753844BACKGROUND
  • 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.

    PMID: 10037110BACKGROUND
  • 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.

    PMID: 9815870BACKGROUND
  • 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.

    PMID: 25164906BACKGROUND
  • 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.

    PMID: 22568773BACKGROUND
  • 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.

    PMID: 20579544BACKGROUND
  • 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.

    PMID: 27388046BACKGROUND
  • 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.

    PMID: 10694528BACKGROUND
  • 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.

    PMID: 8392653BACKGROUND

MeSH Terms

Conditions

Orthostatic IntolerancePostural Orthostatic Tachycardia SyndromeSyncopePrimary Dysautonomias

Condition Hierarchy (Ancestors)

Autonomic Nervous System DiseasesNervous System DiseasesNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsUnconsciousnessConsciousness DisordersNeurobehavioral Manifestations

Study Officials

  • Raffaello Furlan, Prof

    Humanitas Research Hospital; Humanitas University

    STUDY DIRECTOR
  • Franca Barbic, MD

    Humanitas Research Hospital; Humanitas University

    STUDY CHAIR
  • Dana Shiffer, MD

    Humanitas Research Hospital IRCCS, Rozzano-Milan

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 4, 2019

First Posted

November 17, 2020

Study Start

November 10, 2019

Primary Completion

June 30, 2022

Study Completion

December 30, 2022

Last Updated

June 30, 2022

Record last verified: 2021-06

Locations