Transcutaneous Vagus Nerve Stimulation in Heart Failure (TRANSFER)

January 28, 2025 updated by: Istituti Clinici Scientifici Maugeri SpA

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • PV
      • Pavia, PV, Italy, 27100
        • Istituti Clinici Scientifici Maugeri IRCCS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: active tVNS
Patients randomized to active treatment will be instructed to receive the stimulation at the tragus
Device: Active tVNS
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).
Placebo Comparator: sham tVNS
Patients randomized to active treatment will be instructed to receive the stimulation at the ear lobe
Device: Sham tVNS
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heart Rate
Time Frame: 6 months
beats/min
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Baroreflex Sensitivity
Time Frame: 6 months
ms/mmHg
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituti Clinici Scientifici Maugeri SpA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2020

Primary Completion (Actual)

September 30, 2024

Study Completion (Actual)

December 31, 2024

Study Registration Dates

First Submitted

February 28, 2023

First Submitted That Met QC Criteria

March 15, 2023

First Posted (Actual)

March 29, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 28, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CE 2182
  • RF-2016-02364803 (Other Grant/Funding Number: Italian Ministry of Health)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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