TRAnscutaneous vaGUS Nerve Stimulation in Patients With Chronic Heart Failure

Heart Failure Clinical Trial

— TRAGUS-HF  

Official title:

TRAnscutaneous vaGUS Nerve Stimulation in Patients With Chronic Heart Failure

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06355388
• Other study ID #: TRAGUSHF
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 1, 2024
• Est. completion date: May 1, 2027

Study information

• Verified date: April 2024
• Source: Fondazione Toscana Gabriele Monasterio
• Contact: Claudio Passino, MD
• Phone: 050 3152191
• Email: passino[@]ftgm.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To verify the efficacy of transcutaneous vagus nerve stimulation (tVNS) on and autonomic balance in patients with chronic heart failure and reduced (HFrEF) or mildly reduced (HFmrEF) left ventricular ejection fraction. The study hypothesis is that tVNS increases baroreflex gain, with consequent benefits on sympathovagal balance (at short- and mid-term), and on quality of life and bio-humoral parameters (at mid-term).

Description:

Pilot phase: comparing the effects of right- (10-minute) vs. left-sided tVNS (10-minute) on BRS and heart rate variability (HRV) in a subset of patients.

Short-term phase: comparing the effects of active- (10-minute) vs. sham-tVNS (10-minute) on BRS, HRV, and sympathetic nerve activity.

Mid-term phase: comparing the effects of active- (4-week) vs- sham-tVNS (4-week) on BRS, HRV, biomarkers, exercise performance, and cardiac function.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: May 1, 2027
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria

• Aged =18 years;

• Ability to consent to enrollment;

• Diagnosis of chronic heart failure (CHF= and left ventricular ejection fraction <50% according to the latest European guidelines.

Exclusion criteria

• History of acute coronary syndrome within 3 months of enrollment;

• Clinical need to modify CHF therapy during the study;

• History of recurrent syncope, orthostatic hypotension, severe bradycardia (average heart rate <50 bpm), or second or third-degree atrioventricular block;

• Neurological conditions characterized by dysautonomia (e.g., Parkinson's disease);

• Unstable major psychiatric disorders or treatment with psychoactive drugs or drugs that can act on the autonomic nervous system (e.g., antidepressants, antipsychotics, opioids, benzodiazepines);

• Uncontrolled thyroid disorders;

• Active neoplasia;

• Severe renal insufficiency (estimated glomerular filtration rate <15 ml/min/1.73 m2);

• Moderate or severe chronic obstructive pulmonary disease (FEV1/FVC <70% of predicted and FEV1 <70%);

• Liver insufficiency (AST/ALT >100 U/L and/or gamma-GT >150 U/L);

• Participation in other clinical studies in the 3 months preceding;

• Women in pregnancy, breastfeeding, or of childbearing age not following adequate contraception (the woman must agree to abstain from heterosexual intercourse or use at least two effective contraceptive measures such as bilateral tubal ligation, male sterilization, use of hormonal contraceptives that inhibit ovulation, intrauterine devices releasing hormones, copper intrauterine devices; all barrier devices must be used in combination with a spermicidal cream).

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Device:
• Active tVNS
As for the short-term phase, the ear clip of the "Parasym" device (Parasym, London, United Kingdom), containing the stimulation electrode, will be positioned at the level of the patient's tragus, and a 10-minute stimulation will be initiated with a pulse width of 200 µs, a frequency of 30 Hz, and an intensity of one mA lower than the patient's sensitivity threshold. As fort he mid-term phase, a device will be given to the patient, which will be instructed to position the ear clip of the device at the level of the tragus and to set stimulation parameters as established in the laboratory (see above). Each patient will be asked to undergo at least one hour daily stimulation for a period of 4 weeks, reporting on a diary the timing and details of the each session.
• Sham tVNS
As for the short-term phase, the ear clip of the "Parasym" device (Parasym, London, United Kingdom), containing the stimulation electrode, will be positioned at the level of the patient's tragus for 10-minute but no current will be delivered. As fort he mid-term phase, a device (configured to withhold power delivery) will be given to the patient, which will be instructed to position the ear clip of the device at the level of the tragus and to set stimulation parameters as established in the laboratory (see above). Each patient will be asked to undergo at least one hour daily stimulation for a period of 4 weeks, reporting on a diary the timing and details of the each session.

Locations

Country	Name	City	State
Italy	Michele Emdin	Pisa	Pi

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione Toscana Gabriele Monasterio	Azienda Ospedaliera Città della Salute e della Scienza di Torino

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mean change in MSNA burst incidence (bursts/100 heartbeats)	Assessed through peroneal nerve microneurography (as previously detailed in doi: 10.3389/fphys.2022.934372).	10 minutes (short-term effect)
Other	Mean change in peak O2 consumption (mL/Kg/min)	Assessed through cardiopulmonary exercise test	4 weeks (mid-term effect)
Primary	Mean change in baroreflex gain (ms/mmHg)	Barorefex gain will be calculated calculated as the ratio between the standard deviation of RR intervals (ms) and systolic blood pressure (mmHg)	10 minutes (short-term effect)
Primary	Mean change in baroreflex gain (ms/mmHg)	Barorefex gain will be calculated calculated as the ratio between the standard deviation of RR intervals (ms) and systolic blood pressure (mmHg)	4 weeks (mid-term effect)