Cardiac Neuromodulation Therapy (CNT) "Washout" Sub-Study

NCT ID: NCT05086523

Last Updated: 2022-11-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-27
• Study Completion Date: 2023-09-30

Brief Summary

This washout protocol is structured as a sub-study for patients willing to participate after finishing the double blind randomised phase of the clinical trial, NCT02837445. Devices will be turned off for a week approximately. Patients will have their PHC programmed to automatically turn off 24 hr after a medical and technical visit and remain in regular pacing. Ambulatory recording of the BP will start at the end of the visit, and continue for 24 hr after the turn off time (48 hr recording). Conversely, patients will return at the end of the first week, when a second 48 hr recording will be initiated, this time, the PHC will be programmed to turn on 24 hr later. The recordings therefore will provide data of the ON to OFF transition for the evaluation of the residual effect of PHC after 24 h and after week.

Detailed Description

As detailed in protocol CS-03, the BackBeat Moderato system applies standard pacing signals according to a specially timed, alternating sequence short and longer atrioventricular (AV) delays, to reduce blood pressure as a treatment for hypertension. The algorithm that governs the delivery of these pacing signals is referred to as Cardiac Neuromodulation Therapy (CNT) and the signals are referred to as Programable Hypertension Control (PHC) signals, (refer to Clinical Evaluation of Safety and Effectiveness of the BackBeat Medical Moderato System in Patients With Hypertension: A Double-Blind Randomized Trial, NCT02837445) As currently used, CNT requires continuous right ventricle (RV) pacing. However, due to potentially long-term effects of CNT on baroceptor function, intermittent deactivation of CNT could reduce the overall amount of pacing without loss of efficacy. Support for this hypothesis comes from a preclinical testing of CNT that was detailed in "Chapter II - Pre-Clinical Testing" of the approved Investigator Brochure. BackBeat Medical conducted a chronic feasibility study in 4 dogs with hypertension induced by renal artery banding which were implanted with a Moderato IPG for 4 months. Results from this study showed that when CNT was turned off after 30 days of continuous CNT, there was a very slow increase in systolic pressure, approaching pre-therapy levels only several weeks later. A 50% residual effect remained at 20 days, with a total washout period of approximately 30 days.

One possible explanation for this observation is that the signal beneficially changes the pressure"set point" of the baroceptor reflexes. Changes in the set point could result from changes at the level of either the pressure sensor in the carotid sinus or within the pressure regulatory region of the central nervous system; namely the nucleus tractus solitarius (NTS) in the medulla oblongata.

This sub-study aims to evaluate whether and for how long the blood-pressure lowering effect of CNT persists following its cessation in patients who have been treated with CNT for a prolonged period of time.

Conditions

Hypertension,Essential; Systolic Hypertension

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Interventions

Programmable Hypertension Control (BackBeat Moderato)

Programmable Hypertension Control can be turned OFF without affecting regular pacing

Intervention Type: DEVICE

Pacing (BackBeat Moderato)

Programmable Hypertension Control can be turned OFF without affecting regular pacing

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Subject is implanted with a Moderato® implantable pulse generator (IPG) and is being followed by the site per standard of care.
• Subject has an average office systolic blood pressure > 130 mmHg and < 170 mmHg at the sub-study screening visit.

Exclusion Criteria

• Subject has permanent atrial fibrillation.
• Subject had significant paroxysmal atrial fibrillation/flutter burden (defined as >25% of beats) in the past month. Atrial fibrillation/flutter burden will be determined by interrogation of the Moderato pulse generator.
• Subject experienced neurological events (stroke or TIA) within the past year. Subject have had a serious adverse event classified as related to CNT or the Backbeat Moderato device.
• Female subject who is pregnant, breast-feeding, intends to become pregnant or has the possibility of becoming pregnant during the conduct of the study and is not willing to use contraception during the study.
• Subject cannot or is unwilling to provide informed consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BackBeat Medical Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Na Homolce Hospital

Prague, , Czechia

Site Status: COMPLETED

Semmelweis University Heart and Vascular Center

Budapest, , Hungary

Site Status: COMPLETED

Szpital Kliniczny Przemiemienia Panskiego

Poznan, , Poland

Site Status: NOT_YET_RECRUITING

Pomeranian Medical University Hospital no. 2

Szczecin, , Poland

Site Status: NOT_YET_RECRUITING

Samodzielnym Publicznym Centralnym Szpitalem Klinicznym

Warsaw, , Poland

Site Status: NOT_YET_RECRUITING

Silesian Center for Heart Diseases

Zabrze, , Poland

Site Status: RECRUITING

Countries

Czechia; Hungary; Poland

Central Contacts

Yuval Mika, Ph.D.

Role: CONTACT

ymika@orchestrabiomed.com

+18569123155

Norbert Rosenthal, B.Sc.

Role: CONTACT

nrosenthal@orchestrabiomed.com

+491792482543

Facility Contacts

Przemyslaw Mitkowski, Prof.

Role: primary

przemyslaw.mitkowski@skpp.edu.pl

Jaroslaw Kazmierczak, Prof.

Role: primary

jar.kazmierczak@o2.pl

Marcin Grabowski, M.D.

Role: primary

marcin.grabowski@wum.edu.pl

Adam Sokal, MD, PhD

Role: primary

asokal20@gmail.com

References

Kandzari DE, Kario K, Mahfoud F, Cohen SA, Pilcher G, Pocock S, Townsend R, Weber MA, Bohm M. The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. Am Heart J. 2016 Jan;171(1):82-91. doi: 10.1016/j.ahj.2015.08.021. Epub 2015 Sep 11.

Reference Type: BACKGROUND

PMID: 26699604 (View on PubMed)

Bohm M, Townsend RR, Kario K, Kandzari D, Mahfoud F, Weber MA, Schmieder RE, Tsioufis K, Hickey GL, Fahy M, DeBruin V, Brar S, Pocock S. Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clin Res Cardiol. 2020 Mar;109(3):289-302. doi: 10.1007/s00392-020-01595-z. Epub 2020 Feb 7.

Reference Type: BACKGROUND

PMID: 32034481 (View on PubMed)

Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, Ewen S, Tsioufis K, Tousoulis D, Sharp ASP, Watkinson AF, Schmieder RE, Schmid A, Choi JW, East C, Walton A, Hopper I, Cohen DL, Wilensky R, Lee DP, Ma A, Devireddy CM, Lea JP, Lurz PC, Fengler K, Davies J, Chapman N, Cohen SA, DeBruin V, Fahy M, Jones DE, Rothman M, Bohm M; SPYRAL HTN-OFF MED trial investigators*. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017 Nov 11;390(10108):2160-2170. doi: 10.1016/S0140-6736(17)32281-X. Epub 2017 Aug 28.

Reference Type: BACKGROUND

PMID: 28859944 (View on PubMed)

Other Identifiers

CNT Washout substudy

Identifier Type: -

Identifier Source: org_study_id