Positive Airway Pressure Gas Modulator - A Novel Method to Treat Central Sleep Ap

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$1,542,580.00
Award Year:
2010
Program:
SBIR
Phase:
Phase II
Contract:
4R44HL092686-02
Award Id:
89318
Agency Tracking Number:
HL092686
Solicitation Year:
n/a
Solicitation Topic Code:
NHLBI
Solicitation Number:
n/a
Small Business Information
4415 EUCLID AVE, CLEVELAND, OH, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
557510625
Principal Investigator:
HANI KAYYALI
(216) 619-5911
HKAYYALI@CLEVEMED.COM
Business Contact:
AKRAM KAYYALI
() -
hkayyali@clevemed.com
Research Institution:
n/a
Abstract
DESCRIPTION (provided by applicant): Sleep apnea is a major public health problem but traditional treatments have focused mostly on resolving obstructive sleep apnea (OSA) as demonstrated by the plethora of obstruction-motivated therapies like positive air way pressure, oral appliances, and others. However, more troubling forms of sleep apnea exist like those that are mediated by chemoreflex instability; yet, treatment for such disease states remain inadequate. Central apneas and periodic breathing are the c lassic polysomnographic markers of strong chemoreflex mediation of sleep apnea. Recently, another variation called complex sleep apnea has been described, which is characterized by sustained induction of central apneas or severe periodic breathing during positive pressure titration for what seems to be an obstructive disease on the diagnostic polysomnogram. The number of the affected population is large with Complex Sleep apnea alone estimated at over 1.5 million patients. We propose to develop a new clas s of positive airway pressure devices that will be based on preventing chemoreflex instability by carefully maintaining carbon dioxide (CO2) levels just above the CO2-dependent apneic threshold. We will call this technology: Positive Airway Pressure Gas Mo dulation (PAPGAM). We have conducted significant preliminary experiments demonstrating that prevention of hypocapnia during the application of positive airway pressure therapies can restore normal breathing to patients who were resistant to current therapi es. The overarching goal of Phase I is to confirm the sustained efficacy and lack of toxicity of PAPGAM by testing more patients over multiple nights, while Phase II will complete device development and conduct an extensive clinical trial. The extensive pr eliminary results, which demonstrated an appreciable level of safety and efficacy testing combined with the excellent investigative team and timeliness of the project have encouraged us to submit a Fast Track application instead of Phase I only. Phase I wi ll assess in subjects with chemoreflex dependent sleep apnea: 1) The development of tolerance, or lack of, to the PAPGAM over a two-week period. 2) The safety profile of the PAPGAM in relation to hemodynamic, respiratory, autonomic and metabolic variables. Phase II will complete the development of PAPGAM hardware and software design including regulatory and medical standards testing and conduct extensive medium term efficacy and toxicity clinical testing. We believe, our approach will create a paradigm shif t in the treatment of sleep-breathing disorders that will benefit patients with and without significant comorbidities such as heart failure. Our goal is in strong agreement with NIH's recommendation for future sleep disorders research as clearly indicated in the most recent National Center for Sleep Disorders Research Plan. We have assembled world renowned experts in the field to execute this project. Dr. Robert Thomas from Beth Israel Deaconess Medical Center, Boston and Dr. Safwan Badr from Wayne State Un iversity School of Medicine, Detroit, are experts not only in the field of sleep disordered breathing but have been leading the emerging field of chemoreflex dependent sleep apnea. PUBLIC HEALTH RELEVANCE: Sleep apnea is a major public health problem but t raditional treatments have focused mostly on resolving obstructive sleep apnea (OSA) as demonstrated by the plethora of obstruction-motivated therapies like positive airway pressure, oral appliances, and others. However, more troubling forms of sleep apnea exist like those that are mediated by chemoreflex instability; yet, treatment for such disease states remain inadequate. Central apneas and periodic breathing are the classic polysomnographic markers of strong chemoreflex mediation of sleep apnea. Recentl y, another variation called complex sleep apnea has been described, which is characterized by sustained induction of central apneas or severe periodic breathing during positive pressure titration for what seems to be an obstructive disease on the diagnos tic polysomnogram. The number of the affected population is large with Complex Sleep apnea alone estimated at over 1.5 million patients. We propose to develop a new class of positive airway pressure devices that will be based on preventing chemoreflex inst ability by carefully maintaining carbon dioxide (CO2) levels just above the CO2-dependent apneic threshold. We will call this technology: Positive Airway Pressure Gas Modulation (PAPGAM). We have conducted significant preliminary experiments demonstrating that prevention of hypocapnia during the application of positive airway pressure therapies can restore normal breathing to patients who were resistant to current therapies. The overarching goal of Phase I is to confirm the sustained efficacy and lack of to xicity of PAPGAM by testing more patients over multiple nights, while Phase II will complete device development and conduct an extensive clinical trial. The extensive preliminary results, which demonstrated an appreciable level of safety and efficacy testi ng combined with the excellent investigative team and timeliness of the project have encouraged us to submit a Fast Track application instead of Phase I only. Phase I will assess in subjects with chemoreflex dependent sleep apnea: 1) The development of tol erance, or lack of, to the PAPGAM over a two-week period. 2) The safety profile of the PAPGAM in relation to hemodynamic, respiratory, autonomic and metabolic variables. Phase II will complete the development of PAPGAM hardware and software design includin g regulatory and medical standards testing and conduct extensive medium term efficacy and toxicity clinical testing. We believe, our approach will create a paradigm shift in the treatment of sleep-breathing disorders that will benefit patients with and wit hout significant comorbidities such as heart failure. Our goal is in strong agreement with NIH's recommendation for future sleep disorders research as clearly indicated in the most recent National Center for Sleep Disorders Research Plan. We have assembled world renowned experts in the field to execute this project. Dr. Robert Thomas from Beth Israel Deaconess Medical Center, Boston and Dr. Safwan Badr from Wayne State University School of Medicine, Detroit, are experts not only in the field of sleep disord ered breathing but have been leading the emerging field of chemoreflex dependent sleep apnea.

* information listed above is at the time of submission.

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