Preload and Autonomic Responses With Cardiac Neuromodulation Therapy (CNT) (CS-06) (CS-06)

Pressure-Volume (PV) Measurements for Evaluating the Changes in the Ventricular Preload and Autonomic Nervous System Using BackBeat Medical Cardiac Neuromodulation Therapy (CNT) Signals in an Acute Study

This investigation will evaluate the effect of RV pacing lead position on cardiac function and the modulation of the autonomic nervous system with Cardiac Neuromodulation Therapy (CNT) pacing signals. The study will be performed acutely prior to a pacemaker implant.

Study Overview

• Status: Recruiting
• Conditions: Bradycardia; Hypertension, Systolic
• Intervention / Treatment: Device: Moderato IPG's CNT pacing signals; Device: CD Leycom Pressure/Volume Combination Catheters

Detailed Description

Subjects indicated for a dual chamber pacemaker implant or replacement who are not 100% dependent on right ventricular pacing may be eligible to participate in the study.

This investigation will evaluate the effect of RV pacing lead position on cardiac function and the modulation of the autonomic nervous system using Cardiac Neuromodulation Therapy (CNT) pacing signals at different positions of the RV pacing lead.

A standard conductance catheter will be introduced through the femoral artery and advanced into the left ventricle to measure cardiac volumes and pressure.

Arterial blood pressure will be measured from the other femoral artery with an additional sheath.

The Moderato® IPG will be used to generate Cardiac Neuromodulation Therapy (CNT) signals and deliver them to the patient through the cable and leads. A range of CNT signal parameters will be used to assess the effect on sympathetic activity at different positions of the RV pacing lead. Ventricular pressure and volume readings from the conductance catheter and arterial pressure readings will be recorded and analyzed to assess the effect of CNT signals on cardiac function, sympathetic activity and blood pressure.

The effects of CNT signal over a range of parameter settings will be studied for the different RV lead positions.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yuval Mika, PhD; Phone Number: +18569123155; Email: ymika@orchestrabiomed.com
• Study Contact Backup: Name: Norbert Rosenthal; Phone Number: +491792482543; Email: nrosenthal@orchestrabiomed.com

Study Locations

• Czechia
  • Praha, Czechia, 15030
    • Recruiting
    • Na Homolce Hospital
    • Contact: Petr Neuzil, MD, PhD; Phone Number: +420 257272211; Email: Peter.Neuzil@homolka.cz
    • Contact: Libor Dujka, MD; Phone Number: +420731486352; Email: libor.dujka@homolka.cz
    • Principal Investigator: Petr Neuzil, MD, PhD
    • Sub-Investigator: Filip Malek, MD, PhD
    • Sub-Investigator: Jan Petru, MD
    • Sub-Investigator: Milan Chovanec, MD
    • Sub-Investigator: Libor Dujka, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject is ≥ 18 years of age
2. Subject requires implantation or replacement of a dual chamber pacemaker or requires an upgrade from a single chamber to a dual chamber pacemaker
3. Subject has known Hypertension
4. Subject is willing and able to comply with the study and procedures.

Exclusion Criteria:

1. Subject has symptoms of heart failure, NYHA Class II or greater
2. Subject has significant (>2+) mitral regurgitation, aortic regurgitation or aortic stenosis.
3. Subject has permanent atrial fibrillation
4. Subject has atrial fibrillation on the day of the study.
5. Subject has hypertrophic cardiomyopathy, restrictive cardiomyopathy or interventricular septal thickness ≥15 mm
6. Subject is on dialysis
7. Subject has a history of prior neurological events (stroke or TIA) within the past year or a neurological event (stroke or TIA) at any prior time that has resulted in residual neurologic deficit.
8. Subject has a history of autonomic dysfunction
9. Women who are pregnant or breast-feeding
10. Subject cannot or is unwilling to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Acute CNT pacing signals testing; Acute study procedure will be carried out prior to a pacemaker implantation or replacement: pacemaker Right Atrial (RA) and Right Ventricular (RV) leads will be positioned according to standard procedure for pacemaker implant and connected to a Moderato® System IPG, via a single use, sterile Pacing System Analyzer (PSA) cable. The Moderato IPG will deliver CNT signals. Furthermore, a standard conductance catheter in the left ventricle will measure cardiac volumes and pressure. Arterial blood pressure will be obtained as well. A range of CNT signal parameters will be used to assess the effect on sympathetic activity at different positions of the RV pacing lead while ventricular pressure and volume and arteial pressure signals will be assesed for cardiac function, sympathetic activity and blood pressure. The effects of CNT signal over a range of parameter settings will be studied for the different RV lead positions.

Device: Moderato IPG's CNT pacing signals; Assesment of cardiac function and sympatheric activity will be obtained simultaneously; Device: CD Leycom Pressure/Volume Combination Catheters; Simultaneous recording of the Pressure, Volume measurements and ECG signals will be done for constant monitoring of intra-ventricular pressure and volume.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of the Moderato CNT pacing signals on cardiac function	Left ventricular pressure (mmHg) and Volume (ml) will be obtained by a multisensor catheter which provides real-time, beat-to-beat intra-ventricular measurement of cardiac function and performance. Data will be used to generate Pressure-Volume Loops, an aknowledged way to describe hemodynamic changes. CNT signals (alternating short and long atrioventicular sequences 40-150 ms) will be delivered at the same by right ventricular pacemaker leads temporarely connected to the Moderato device.	approximately one hour
Effects of CNT pacing signals on blood pressure	Blood pressure (mmHg) will be obtained in parallel with a Millar catheter from the femoral artery througout the study.	aproximately onr hour

Collaborators and Investigators

• Sponsor: BackBeat Medical Inc
• Collaborators: CD Leycom

Publications and helpful links

General Publications

• Yang B, Wang Y, Zhang F, Ju W, Chen H, Mika Y, Aviv R, Evans SJ, Burkhoff D, Wang J, Chen M. Rationale and evidence for the development of a durable device-based cardiac neuromodulation therapy for hypertension. J Am Soc Hypertens. 2018 May;12(5):381-391. doi: 10.1016/j.jash.2018.03.004. Epub 2018 Mar 21.
• Neuzil P, Merkely B, Erglis A, Marinskis G, de Groot JR, Schmidinger H, Rodriguez Venegas M, Voskuil M, Sturmberger T, Petru J, Jongejan N, Aichinger J, Kamzola G, Aidietis A, Geller L, Mraz T, Osztheimer I, Mika Y, Evans S, Burkhoff D, Kuck KH; BackBeat Study Investigators. Pacemaker-Mediated Programmable Hypertension Control Therapy. J Am Heart Assoc. 2017 Dec 23;6(12):e006974. doi: 10.1161/JAHA.117.006974.
• de Roest GJ, Allaart CP, Kleijn SA, Delnoy PP, Wu L, Hendriks ML, Bronzwaer JG, van Rossum AC, de Cock CC. Prediction of long-term outcome of cardiac resynchronization therapy by acute pressure-volume loop measurements. Eur J Heart Fail. 2013 Mar;15(3):299-307. doi: 10.1093/eurjhf/hfs190. Epub 2012 Nov 25.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2020
• Primary Completion (Anticipated): March 31, 2023
• Study Completion (Anticipated): July 31, 2023

Study Registration Dates

• First Submitted: June 30, 2020
• First Submitted That Met QC Criteria: July 3, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Actual): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Bradycardia
• Other Study ID Numbers: BBM MOD PV CS-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No