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

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.

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.