Cardiac Neuromodulation Therapy (CNT) "Washout" Sub-Study
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Outcome Measures
Primary Outcome Measures
- Change in Systolic Blood Pressure (SBP) between baseline (PHC ON) and PHC OFF at two consecutive time points: (a) after one day and (b) after a week of PHC OFF [one week]
The first 24 hr of the first recording will be used to obtain the average for the baseline SBP value. As PHC is automatically turned OFF while the recording continues for another 24 hrs, the latter 24 hr will be used to obtain the average SBP of the first day with PHC OFF. A week later, the first 24 hr of the second recording will be used to obtain the average change in SBP to compare to the baseline (PHC ON).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subject is implanted with a Moderato implantable pulse generator (IPG) and completed participation in the CS-03 clinical study.
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Subject has been treating with continuous, active CNT pacing signals for at least
1 month.
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Subject's CNT signal parameters have been stable for at least 1 month.
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Subject has an average office systolic blood pressure less than 170 mmHg at the sub-study screening visit (with CNT on).
Exclusion Criteria:
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Subject has permanent atrial fibrillation.
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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.
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Subject experienced a 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.
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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.
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Subject cannot or is unwilling to provide informed consent.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Na Homolce Hospital | Praha | Czechia | 15030 | |
| 2 | Semmelweis University Heart and Vascular Center | Budapest | Hungary | 1122 | |
| 3 | Szpital Kliniczny Przemiemienia Panskiego | Poznań | Poland | 61-848 | |
| 4 | Pomeranian Medical University Hospital no. 2 | Szczecin | Poland | 70-111 | |
| 5 | Samodzielnym Publicznym Centralnym Szpitalem Klinicznym | Warsaw | Poland | 02-097 | |
| 6 | Silesian Center for Heart Diseases | Zabrze | Poland | 41-800 |
Sponsors and Collaborators
- BackBeat Medical Inc
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Böhm 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. Erratum in: Clin Res Cardiol. 2020 May;109(5):653.
- Kandzari DE, Kario K, Mahfoud F, Cohen SA, Pilcher G, Pocock S, Townsend R, Weber MA, Böhm 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. Review.
- 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, Böhm 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.
- CNT Washout substudy