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Heart Failure With Preserved Ejection FractionTRANSFERNCT05789147

Transcutaneous Vagus Nerve Stimulation in Heart Failure

A study testing Active tVNS in people with Heart Failure With Preserved Ejection Fraction and Heart Failure With Midrange Ejection Fraction, run by Istituti Clinici Scientifici Maugeri SpA at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
What is being tested?
Active tVNS
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
29 participants
Where
1 siteItaly
Study dates
15 Jun 2020to 31 Dec 2024
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Istituti Clinici Scientifici Maugeri IRCCS

    Pavia, PV, 27100

Other trials in Italy

About this study

Official title: EffecTs of tRanscutaneous vAgus Nerve Stimulation in Heart Failure Patients With Moderately rEduced or preseRved Left Ventricular Function

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.

Read the detailed description

The autonomic nervous system (ANS), through the interaction between the sympathetic and vagal systems, plays a key role in modulating the cardiovascular system. Multiple experimental data and clinical studies have shown that alterations in the activity of the ANS - characterized by a predominant sympathetic modulation associated with reduced vagal modulation - are implicated in the onset and progression of numerous cardiovascular diseases. For example, both an increase in sympathetic activity and a reduction in vagal activity are associated with an increased risk of death after myocardial infarction and heart failure, and a further reduction in vagal activity has been shown to precede the phases of hemodynamic instability (1 -2).

Over the last few years, the modulation of the ANS through the implantation of devices has emerged as a new frontier for the treatment of heart failure (3). Although there is a wide interest in the scientific community for the potential represented by this therapeutic modality, nevertheless the different devices for neuromodulation therapy are implantable devices (whose application requires an invasive procedure) and therefore not free from risks and complications.

Direct stimulation of the vagus nerve by means of a sleeve positioned around the vagus nerve in its right or left cervical portion and controlled by a pacemaker, represents one of the methods proposed in the field of neuromodulation (4).

As for vagal stimulation, this can also be achieved non-invasively by applying an external stimulator in the ear (5). Transcutaneous nerve stimulation is a widely used procedure for the treatment of refractory epilepsy, while there is still limited experience evaluating its cardiovascular effects. Preliminary data in healthy volunteers have shown that: a) transcutaneous vagal stimulation, through the auricle, is able to activate the afferent vagal pathway up to the nucleus of the solitary tract (6), b) non-invasive stimulation of the vagus nerve is able to reduce sympathetic outflow (7). Recent clinical experience suggests its role also in the control of paroxysmal atrial fibrillation (8).

Therefore, non-invasive vagus nerve stimulation could be a promising therapeutic option in the cardiovascular field.

This study aims to evaluate the effects of long-term transcutaneous vagus nerve stimulation (tVNS) on autonomic parameters and other available physiological biomarkers that reflect long-term adjustment of autonomic neural regulation and to correlate the magnitude of the response to the baseline autonomic profile. A preliminary set of experiments will be conducted on healthy subjects to define the best tVNS protocol (in terms of frequency and site of stimulation) to induce acute changes in the autonomic profile.

Being tested
Active tVNS, Sham tVNS

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Active tVNSDevice

    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).

  • Sham tVNSDevice

    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.

Study groups in NCT05789147
Study groupRoleWhat they receive
active tVNSActive comparatorPatients randomized to active treatment will be instructed to receive the stimulation at the tragus
Receives: Device: Active tVNS
sham tVNSPlacebo comparatorPatients randomized to active treatment will be instructed to receive the stimulation at the ear lobe
Receives: Device: Sham tVNS

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Heart Rate

    beats/min

    Measured: 6 months

Secondary outcomes (1)

  1. Baroreflex Sensitivity

    ms/mmHg

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2023
  2. Study start15 Jun 2020
  3. Primary completion30 Sep 2024
  4. Study completion31 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized controlled study to evaluate the effects of 6-month tVNS (1 hour/day) in heart failure patients on autonomic biomarkers.
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05789147
Sponsor's protocol ID
CE 2182
Other IDs
RF-2016-02364803
Acronym
TRANSFER
Status last verified
Jan 2025
First submitted
28 Feb 2023
Last updated
30 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 9482439

  • 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.

    PubMed 9396441

  • 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.

    PubMed 25991804

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

    PubMed 21154273

  • 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.

    PubMed 26381725

  • 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.

    PubMed 25573069

  • 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.

    PubMed 25164906

  • 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.

    PubMed 25744003

  • 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.

    PubMed 9617526

  • 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.

    PubMed 17381425

  • 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.

    PubMed 12095408

  • 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.

    PubMed 39016202

Questions about this trial

What is this clinical trial studying?

A study testing Active tVNS in people with Heart Failure With Preserved Ejection Fraction and Heart Failure With Midrange Ejection Fraction, run by Istituti Clinici Scientifici Maugeri SpA at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Heart Rate (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05789147, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.

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