The Injectrode- An injectable, easily removable electrode as a trial lead for baroreceptor activation therapy to treat hypertension and heart failure

1 Abstract2 Hypertension affects upwards of 25% of adults, and of those individuals with hypertension, it has been3 estimated that between 20 to 30% are resistant to standard pharmacological treatment. Similarly, the 3-year4 mortality rate for patients with functional Class III heart failure with reduced ejection fraction is 30%. Activation5 of the baroreflex through electrical stimulation of the carotid sinus bulb has recently been market approved by6 the Food and Drug Administration to treat both hypertension and heart failure by inducing large systemic7 changes in sympathetic/parasympathetic tone. Unlike vagus nerve stimulation (VNS) which has failed multiple8 double-blinded, randomized and sham controlled Phase III studies (RCT), stimulation of the carotid sinus bulb9 has demonstrated large decreases in blood pressure in RCT vs sham. The failure of VNS is putatively due to 10 activation of motor nerve efferents causing therapy limiting neck muscle activation prior to engagement of 11 parasympathetic efferents to the heart or sensory afferent pathways to the Nucleus of the Solitary Tact (NTS) 12 Despite its success in clinical trials, baroreflex activation therapy (BAT) is a treatment of last resort used only 13 after drug therapies have failed. 14 There are four primary reasons driving the lack of widespread adoption of BAT: 1) the invasiveness of 15 surgical implantation is unattractive to patients with largely asymptomatic uncontrolled hypertension, 2) the 16 complexity of the present implanted system leads to multiple points of failure chronically and dramatically 17 increases the complexity of the supply chain leading to high-profile device recalls in VNS, 3) the general cost of 18 the implanted system is prohibitive, and 4) concurrent activation of the neck muscles still limits therapeutic 19 efficacy in many patients. To overcome these issues, we have developed a novel electrode called the 20 Injectrode®, a syringe injectable, flexible electrode material that conforms to complex structures like a plexus 21 or foramen once injected. We have recently shown the ability to inject on a deep nerve, connect via a simple 22 wire to an Injectrode ‘collector’ that is injected under the skin, and reliably stimulate the deep nerve using a 23 standard inexpensive non-invasive TENS unit without any wire connection spanning the skin. This system has 24 only one passive component to create a conductive conduit from just under the skin to complex neural 25 structures like the plexus formed by the carotid sinus nerve at the internal carotid artery/bulb, greatly reducing 26 the number of chronic failure points leading to adverse events. 27 In this Phase I SBIR, we will optimize and validate and refine the Injectrode concept for less invasive, 28 more robust, and more isolated BAT. 29