Transcutaneous Vagus Nerve Stimulation in Heart Failure

NCT05789147 | Completed

• 2 other identifiers: CE 2182RF-2016-02364803
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Several studies have shown that alterations in autonomic nervous system function are implicated in the onset and progression of numerous cardiovascular diseases. Direct stimulation of the vagus nerve by means of a sleeve placed around the vagus nerve represents one of the methodologies proposed in the field of neuromodulation. This study, which is proposed as a pilot study for further application of the method in subjects with cardiovascular disease aims to verify and consolidate evidence on cardiovascular autonomic effects in patients with heart failure. Vagal stimulation will be achieved noninvasively by applying an external stimulator to the auricular site.

Conditions

Heart Failure With Preserved Ejection Fraction; Heart Failure With Midrange Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Heart Rate

  beats/min

  6 months

Secondary Outcomes (1)

• Baroreflex Sensitivity

  6 months

Study Arms (2)

active tVNS

ACTIVE COMPARATOR

Patients randomized to active treatment will be instructed to receive the stimulation at the tragus

Device: Active tVNS

sham tVNS

PLACEBO COMPARATOR

Patients randomized to active treatment will be instructed to receive the stimulation at the ear lobe

Device: Sham tVNS

Interventions

Active tVNS DEVICE

It is a non-invasive transcutaneous electrical stimulation of the auricular branch of the vagus nerve which innervates the skin of the human ear. These nerve fibers project directly to the solitary tract nucleus (NTS) in the brain stem (6).

active tVNS

Sham tVNS DEVICE

Sham stimulation is obtained by placing the stimulation electrode at the level of the earlobe. The stimulation is therefore administered and perceived in an area not innervated by vagal fibers.

sham tVNS

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Heart failure patients with moderately reduced or preserved ejection fraction
• Sinus rhythm
• New York Heart Association (NYHA) Class II-III

You may not qualify if:

• Patients with implanted cardiac device (ICD, CRT),
• Patients with recent (\< 3 months) cardiac surgery,
• Patients with recent (\< 3 months) myocardial infarction,
• Patients with recent (\< 3 months) revascularization
• Patients with an indication for cardiac surgery within the next 6 months.

Sponsors & Collaborators

• Istituti Clinici Scientifici Maugeri SpA: lead

Study Sites (1)

Istituti Clinici Scientifici Maugeri IRCCS

Pavia, PV, 27100, Italy

Location

Related Publications (12)

• La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet. 1998 Feb 14;351(9101):478-84. doi: 10.1016/s0140-6736(97)11144-8.

  PMID: 9482439 BACKGROUND

• Mortara A, La Rovere MT, Pinna GD, Prpa A, Maestri R, Febo O, Pozzoli M, Opasich C, Tavazzi L. Arterial baroreflex modulation of heart rate in chronic heart failure: clinical and hemodynamic correlates and prognostic implications. Circulation. 1997 Nov 18;96(10):3450-8. doi: 10.1161/01.cir.96.10.3450.

  PMID: 9396441 BACKGROUND

• Schwartz PJ, La Rovere MT, De Ferrari GM, Mann DL. Autonomic modulation for the management of patients with chronic heart failure. Circ Heart Fail. 2015 May;8(3):619-28. doi: 10.1161/CIRCHEARTFAILURE.114.001964. No abstract available.

  PMID: 25991804 BACKGROUND

• Klein HU, Ferrari GM. Vagus nerve stimulation: A new approach to reduce heart failure. Cardiol J. 2010;17(6):638-44.

  PMID: 21154273 BACKGROUND

• Yuan H, Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part II. Headache. 2016 Feb;56(2):259-66. doi: 10.1111/head.12650. Epub 2015 Sep 18.

  PMID: 26381725 BACKGROUND

• Frangos E, Ellrich J, Komisaruk BR. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul. 2015 May-Jun;8(3):624-36. doi: 10.1016/j.brs.2014.11.018. Epub 2014 Dec 6.

  PMID: 25573069 BACKGROUND

• 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: 25164906 BACKGROUND

• Stavrakis S, Humphrey MB, Scherlag BJ, Hu Y, Jackman WM, Nakagawa H, Lockwood D, Lazzara R, Po SS. Low-level transcutaneous electrical vagus nerve stimulation suppresses atrial fibrillation. J Am Coll Cardiol. 2015 Mar 10;65(9):867-75. doi: 10.1016/j.jacc.2014.12.026.

  PMID: 25744003 BACKGROUND

• Maestri R, Pinna GD. POLYAN: a computer program for polyparametric analysis of cardio-respiratory variability signals. Comput Methods Programs Biomed. 1998 Apr;56(1):37-48. doi: 10.1016/s0169-2607(98)00004-2.

  PMID: 9617526 BACKGROUND

• Pinna GD, Maestri R, Torunski A, Danilowicz-Szymanowicz L, Szwoch M, La Rovere MT, Raczak G. Heart rate variability measures: a fresh look at reliability. Clin Sci (Lond). 2007 Aug;113(3):131-40. doi: 10.1042/CS20070055.

  PMID: 17381425 BACKGROUND

• Pinna GD, Maestri R, Raczak G, La Rovere MT. Measuring baroreflex sensitivity from the gain function between arterial pressure and heart period. Clin Sci (Lond). 2002 Jul;103(1):81-8. doi: 10.1042/cs1030081.

  PMID: 12095408 BACKGROUND

• Maestri R, Pinna GD, Robbi E, Cogliati C, Bartoli A, Gambino G, Rengo G, Montano N, La Rovere MT. Impact of optimized transcutaneous auricular vagus nerve stimulation on cardiac autonomic profile in healthy subjects and heart failure patients. Physiol Meas. 2024 Jul 17;45(7). doi: 10.1088/1361-6579/ad5ef6.

  PMID: 39016202 RESULT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized controlled study to evaluate the effects of 6-month tVNS (1 hour/day) in heart failure patients on autonomic biomarkers.

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: March 29, 2023
• Study Start: June 15, 2020
• Primary Completion: September 30, 2024
• Study Completion: December 31, 2024
• Last Updated: January 30, 2025

Record last verified: 2025-01

Locations

IT (1)