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Principal Investigator: Howard Levin
Organization: CORIDEA, LLC
Fiscal Year: 2024
Award: $274,839
Funding agency: National Institute of General Medical Sciences
PROJECT SUMMARY:
Sepsis is one of the leading sources of morbidity and mortality in the US, impacting nearly 1.7 million adults each year
and upwards of 250,000 deaths annually. Septic shock is sepsis characterized by hemodynamic failure, with
exceptionally high mortality ranging from 15-70%.
Septic shock management involves treatment with antibiotics, fluids, and vasopressor therapy. The latter, while effective
at hemodynamic support at high doses, is related to major side-effects including peripheral ischemia leading to injury
or loss of extremities (toes, fingers, etc.), kidney injury, liver shock, multiple-organ failure. Thus, it is common that
survivors of septic shock have a high degree of morbidity due to these side-effects.
The goal of this proposal is to validate a new, minimally invasive approach to producing the beneficial effects of
vasopressor therapy without the side-effects. We propose that left stellate ganglion nerve stimulation (SGNS) can be
used to aid in hemodynamic support during septic shock, and therefore can markedly reduce, or even obviate, the need
for high-dose vasopressor administration.
To make this clinically practical, we have developed a novel, minimally invasive percutaneous approach to left stellate
ganglion nerve stimulation that is controlled via a closed-loop system that is capable of altering stimulation
automatically to changes in hemodynamic and other bio-markers (e.g., arterial pressure, heart rate).
This project will be completed in several sequential stages. For this Phase I SBIR we will demonstrate proof of
physiological concept that left stellate ganglion nerve stimulation in a known sepsis model can 1) provide and sustain a
minimum degree of hemodynamic support (at least 15 mmHg for 30 minutes in mean arterial pressure), 2) that direct
SGNS lowers vasopressor requirements compared to control by 50%. Separately, we will show that percutaneous SGNS
using our proprietary system is safe, feasible and equivalent to direct SGNS in management of septic shock.
Successful completion of the specific aims will lead to the development of a clinical-grade system (stimulator controller
and percutaneous lead) that can be validated and verified for Phase II of the project and evaluated clinical in an early
feasibility IDE trial.
Terms: <21+ years old><Adult><Adult Human><Adverse effects><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Arrhythmia><BP control><BP management><Biological Markers><Blood Pressure><Body System><Cardiac Arrhythmia><Cardiac Chronotropism><Cardiac Output><Caring><Cervicothoracic Ganglion><Cessation of life><Clinical><Death><Development><Devices><Dose><ECG><EKG><Electrocardiogram><Electrocardiography><Extremities><Failure><Fingers><Future><Goals><Grant><Health><Heart Arrhythmias><Heart Rate><Hour><Hypertension><Injury><Injury to Kidney><Intestinal><Intestines><Ischemia><Kidney><Kidney Urinary System><Lead><Left><Limb structure><Limbs><Liquid substance><Liver><Liver Disease Shock Liver><MOF syndrome><Methods><Miscellaneous Antibiotic><Modeling><Morbidity><Morbidity - disease rate><Multiple Organ Dysfunction Syndrome><Multiple Organ Failure><Nerve><Non-Trunk><Organ><Organ System><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pb element><Perfusion><Peripheral><Phase><Physiologic><Physiological><Pre-Clinical Model><Preclinical Models><Randomized><SBIR><Sepsis><Septic Shock><Small Business Innovation Research><Small Business Innovation Research Grant><Source><Stellate Ganglias><Stellate Ganglion><Structure of stellate ganglion><Survivors><System><Techniques><Technology><Time><Toes><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Vasoactive Agonists><Vasoconstrictor Agents><Vasoconstrictor Drugs><Vasoconstrictors><Vasopressor Agents><adulthood><bio-markers><biologic marker><biomarker><blood infection><blood pressure control><blood pressure management><bloodstream infection><bowel><compare to control><comparison control><design><designing><developmental><dosage><extremity injury><extremity trauma><fluid><heart output><heavy metal Pb><heavy metal lead><hemodynamics><hepatic body system><hepatic organ system><high blood pressure><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><improved><improved outcome><injuries><injury to extremity><innovate><innovation><innovative><kidney injury><limb injury><limb trauma><liquid><meeting><meetings><minimally invasive><mortality><multiorgan failure><multiple organ system failure><neural control><neural regulation><neuromodulation><neuromodulatory><neuroregulation><novel><patient oriented outcomes><pressure><randomisation><randomization><randomly assigned><renal><renal injury><risk minimization><secondary outcome><septic><shock liver><side effect><standard of care><success><vasopressor><verification and validation>