Coridea, LLC — Department of Health and Human Services SBIR Phase I: NIDA

Description

Project Summary The United States is in the midst of an opioid overdose crisisAccording to the CDCthere were more thanopioid overdose deaths inaloneThe number of opioid overdose deaths has more than quadrupled sincewith much of this increase attributable to the rise in prescription opioid useThe mechanism of death in opioid overdose is primarily through opioid induced respiratory arrestdefined as the centrally mediated reduction in ventilatory drive after opioid useNaloxonean opioid receptor antagonist that temporarily reverses this processis the first line medication for treatment of opioid overdoseand there have been substantial efforts to reduce overdose deaths in the community by distributing naloxone rescue kits to individuals who are likely to witness opioid overdosesThese efforts have shown significant promiseHowevermany opioid overdose deaths that occur are either unwitnessed or naloxone is not immediately availableAdditional lives could be saved by technologies that can both recognize and treat opioid overdose safely and automaticallyin the absence of a bystanderThe ideal technology would be safereliable and selfcontainedMoreoversuch a device would require no day to day maintenancee greplacing of expired drugplacing of sensorswhich is particularly important in a target population known to have poor compliance with treatmentsOur proposal will validate a new implantable device based approach for rescuing opioid overdose by automatically sensing and reversing the opioid induced respiratory arrest in order to keep the patient stable until definitive treatment with naloxone can be providedThis system would be targeted towards those individuals at the highest risk for opioid overdosethose with a history of overdosepoor response to treatmentusing high opioid dosesconcomitant sedative hypnotic and alcohol useand mental disorders Coridea has previously developed an approach that uses the bodyandapos s natural ability to control respiration by stimulation of the phrenic nerveThe system is a fully implantable pacemaker like device that is currently used for the treatment of central sleep apnea in heart failureand has been shown to be safe and effective for this purposeIt consists of a transvenous pacing lead and an implantable pacemaker like pulse generatorIt can sense specific phases patterns of respiration and then stimulate the phrenic nerve to break the intermittent pattern of sleep disordered breathing that is characteristic of central sleep apnea in heart failureHoweverthis device has never been tested in the context of prolonged respiratory depression arrestwhich is characteristic of opioid overdoseThe ability to fully support respiration has been previously shown using a surgically implanted phrenic nerve cuffbut not with a less invasivetransvenous designAnother novel aspect proposed in this grant is the design and development of a software algorithm to automatically detect and respond to critical respiratory depression and arrestOur eventual clinical device will be placed via a simpleminute procedurevery similar to the currently clinically used cardiac pacemakers or neurostimulators for painin the catheterization laboratory under conscious sedation and local anesthesia with patients able to go home the same dayThis project will be completed in sequential stagesAs deliverables for the Phase I SBIRwe will demonstrate the proof of concept by determining and optimizing the parameters of unilateral transvenous phrenic nerve stimulation required to generate a physiological pattern of respiration sufficient to stabilize gas exchange while maintaining airway patency and maintain blood oxygenation levels in an animal model of opioid induced respiratory arrestIn parallelwe will also validate a method an index for detecting inadequate respiration using transthoracic impedanceUsing the results obtained in the Phase I proof of concept studiesthe future Phase II SBIR deliverables will include design and development of a software algorithm to combine automatic detection and treatment of respiratory depression arrestThe detection algorithm will be optimized for energy efficiency to enable incorporation into a small implantable pulse generatorFollowing the completion of Phase IIwe will seek to fund feasibility clinical trial using a combination of venture and or industry fundingpotentially also as matching funds for a Phase IIb SBIR submissionUltimatelya fully implantableclinically usable system will be developed that incorporates the ability to automatically calland provide GPS coordinates to responders to locate the overdosed patient Project Narrative The United States is in the middle of a fatal and growing opioid overdose epidemicIn this SBIR we will develop an implantableself contained solution for unwitnessed opioid overdose by specifically targeting the critical pathophysiological process that causes deathcentrally induced hypoventilation and apneaWe believe that this therapy will significant reduce the mortality and morbidity associated with opiate overdoses