Effects of Early Vagus Nerve Stimulation on Infarct Damage and Functioning After Acute STEMI

NCT06865716 | Active Not Recruiting

• 1 other identifier: 169-21-BNZ
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate whether early non-invasive vagus nerve stimulation (nVNS) can reduce infarct damage and improve functioning after acute ST-elevation myocardial infarction (STEMI). It will assess the safety and effectiveness of nVNS in improving cardiac outcomes. The main questions it aims to answer are:

• Does nVNS improve short-term prognosis post-STEMI by enhancing heart rate variability (HRV) and reducing inflammation?
• Does nVNS reduce infarct size, improve left ventricular function, and lower inflammatory markers compared to sham stimulation? Participants will be randomly assigned to one of two groups:
• Experimental group: Receive standard care plus nVNS for 60 minutes at the right ear using the Parasym device under ECG monitoring.
• Control group: Receive standard care plus sham nVNS (placebo-like procedure without stimulation). Participants will undergo stimulation once for 60 minutes post-percutaneous coronary intervention (PCI), and be monitored for adverse reactions like bradycardia, with immediate cessation if needed. Key study details:
• Inclusion criteria: Adults aged 25-75 years with confirmed STEMI (clinical signs and elevated troponin).
• Exclusion criteria: Bradycardia (HR \< 50 bpm), extensive anterior MI, hypotension, or severe cardiac/medical conditions.
• Intervention parameters: Stimulation targeting the auricular branch of the vagal nerve with 200µs pulse width, 20Hz frequency, and adjustable intensity (10-50mA), remaining below the pain threshold. Outcomes measured:
• Primary outcomes: Wall motion score index (WMSI) and left ventricular ejection fraction (LVEF).
• Secondary outcomes: HRV metrics, troponin levels, inflammatory markers (CRP, NLR), atrial fibrillation events, hospitalization duration, one-month survival, quality of life (HeartQOL scale), and one-year survival. Statistical analysis: Researchers will compare baseline characteristics using t-tests and chi-square tests. Main analyses will involve repeated measures mixed-design ANOVA and multivariate ANOVA. Moderation analysis will assess the influence of the experimental condition on inflammation and clinical outcomes. Ethical considerations: The study complies with Israeli Ministry of Health guidelines for emergency clinical trials. Participants will provide verbal consent followed by written consent. Ethical approval was granted by the IRB of Bnai Zion Medical Center, Haifa, Israel (Approval No. 0169-21-BNZ).

Conditions

ST Elevation Myocardial Infarction (STEMI)

Keywords

RCT; Non invasive vagal nerve stimulation; STEMI; Cardiac Functioning

Outcome Measures

Primary Outcomes (2)

• Wall Motion Score Index

  The wall motion score index (WMSI) numerically sums the average scores for all left ventricular segments into a single parameter. The prognostic value of WMSI has been investigated in small cohorts of patients with acute myocardial infarction, suggesting superiority to LVEF in predicting mortality

  One to 2 days after stimulation: 24-48 hours post-stimulation

• Left ventricular ejection fraction (LVEF)

  LVEF is the fraction of chamber volume ejected in systole (stroke volume) in relation to the volume of the blood in the ventricle at the end of diastole (end-diastolic volume). Stroke volume is calculated as the difference between EDV and end-systolic volume (ESV). This activity reviews the calculation of LVEF, its clinical relevance and highlights the role of the interprofessional team in managing patients with depressed LVEF.

  One to 2 days after stimulation: 24-48 hours post-stimulation

Secondary Outcomes (8)

• survival

  one month after the intervention and one year after

• quality of lifeQuality of life will be assessed using the Heart Disease-Specific Quality of Life Questionnaire (HeartQOL).

  Data will be collected 24 hours after the intervention and one month after discharge.

• inflammatory markers of CRP

  Baseline (before intervention), 24 hours post-intervention and 48 hours post-intervention .

• inflammatory markers of Neutrophil-to-Lymphocyte Ratio (NLR)

  Baseline (before intervention), 24 hours post-intervention and 48 hours post-intervention

• Troponin

  Baseline (before intervention), 24 hours post-intervention and 48 hours post-intervention

Study Arms (2)

Post PCI STEMI patients treated with early active noninvasive vagus nerve stimulation

EXPERIMENTAL

The patients received 60 minutes of electrical vagus nerve stimulation via electrode attached to the ear.

Device: Active noninvasive vagus nerve stimulation

Post PCI STEMI patients received the clip stimulator on the lower ear lobe without stimulation

SHAM COMPARATOR

Post PCI STEMI patients in the control arm received the clip stimulator on the lower ear lobe without stimulation

Other: Chum electrode attached to patient's lower ear lobe

Interventions

Active noninvasive vagus nerve stimulation DEVICE

The stimulation parameters include a 200µs stimulation width, at an intensity level of 10-50ma (adjusted for patient-comfort), at a frequency of 20Hz during 60min .

Post PCI STEMI patients treated with early active noninvasive vagus nerve stimulation

Chum electrode attached to patient's lower ear lobe OTHER

The clip stimulator is attached to the patient's lower ear lobe without stimulation.

Post PCI STEMI patients received the clip stimulator on the lower ear lobe without stimulation

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Having had an MI verified by clinical signs (e.g., pain in the chest, left arm, left shoulder), ST-elevation MI (STEMI) and clinically significant elevations of troponin values (cut-off value 19 ng/l or using sex-specific cut-off values of 14ng/l for women and 22ng/l for men.
• Between 25-75 years of age.
• Patients with Intra-Aortic Balloon.

You may not qualify if:

• Heart rate (HR) \< 50 bpm (bradycardia)
• Extensive anterior MI: According to infarct size criteria: KILLIP III \& KILLIP IV of Heart Failure following MI is defined as Extensive anterior MI.
• Hypotension (systolic blood pressure \< 90mmHg).
• Sildenafil treatment.
• Diagnosed with Atrial Fibrillation.
• Diagnosed with Ventricular arrythmias not including Accelerated Idio Ventricular Rhythm (AIVR).
• Anaesthetize patient.
• Mechanical ventilated patient.
• Participation in another trial

Sponsors & Collaborators

• Bnai Zion Medical Center: lead
• University of Haifa: collaborator
• University of Oklahoma: collaborator

Study Sites (1)

Bnai Zion Medical Center, 47 Golomb Street, Cardiology Department Main Building, Haifa, Israel

Haifa, Haifa District, 3104802, Israel

Location

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The participants did not know if they were receiving actual stimulation or not. and the ECHO technician who calculated the ECHO results also did not know the arm of the patient
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the cardiology and cardiac care unit

Study Record Dates

• First Submitted: January 19, 2025
• First Posted: March 10, 2025
• Study Start: October 1, 2023
• Primary Completion: January 5, 2025
• Study Completion: December 30, 2025
• Last Updated: March 10, 2025

Record last verified: 2025-03

Locations

IL (1)