Medschool, ANE, Research, Drug Development & Safety

Ketamine has been approved by the Food and Drug Administration (FDA) for use in anesthesia, and it’s often used off-label for pain management. There is significant anecdotal and published evidence depicting a favorable safety profile and a strong analgesic effect. However, rigorous pre-clinical and clinical studies are required to gain analgesic indication and allow widespread use. Furthermore, for ketamine to become a suitable pain medication for the battlefield, it is necessary to develop a method of administration that is optimized for military use and allows easy self-administration. The intranasal device and formulation developed in this project offer an optimal solution for both military and civilian applications.

The goal of this collaborative effort lead by Dr. Bedocs and Dr. Lee, and carried out with multiple industry partners, is to develop IN ketamine for the treatment of moderate to severe acute pain and secure FDA labeling for analgesic indication. In collaboration with Lincoln Therapeutics, LLC. the safety and effectiveness of IN ketamine will be demonstrated in a preclinical toxicology study, followed by human Phase 1 and Phase 2b/3 clinical trials to provide evidence to support an application for FDA approval. The projected results are that IN ketamine is safe, with no or limited adverse effects, and efficacious for the relief of moderate-severe acute pain compared to placebo. 

• Lead Researchers: Peter Bedocs, MD, PhD (peter.bedocs.ctr@usuhs.edu); Jong Lee, MD (jong.lee@usuhs.edu)

Treatment of combat related injuries has been historically predicated in the use of strong opioids. However, the decrease in of the psychomotor reactions due their side effects is disadvantageous to the successful completion of the mission and the service member survival. USUHS, in partnership with OYE Therapeutics, Inc. (focusing on their OYE-1 compound, currently undergoing FDA approval as an agent that accelerates emergency and recovery from anesthesia), have come together to evaluate their compound as a portable and easy to use agent that can reverse these adverse effects, while preserving pain control, improving physiologic resilience and optimizing decision-making combat capabilities.

• Lead Researchers: Jong Lee, MD (jong.lee@usuhs.edu); Peter Bedocs, MD, PhD (peter.bedocs.ctr@usuhs.edu)

The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. In this collaboration led by the University of North Carolina a modular RNA-DNA-based anticoagulant platform was developed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a “kill-switch” mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, a set of anticoagulant fibers were designed and tested that carry different thrombin-binding aptamers. All fibers are immunoquiescent, as confirmed in freshly collected human peripheral blood mononuclear cells. The anticoagulation is first confirmed in the blood of human donors from the U.S. and Brazil, then we confirm the efficacy and safety of the “kill-switch” mechanism in vivo in murine and porcine models. 

• Lead Researchers: Peter Bedocs, MD, PhD (peter.bedocs.ctr@usuhs.edu)

Worldwide, trauma is the leading cause of death for those under the age of 45. And uncontrolled bleeding during the first six hours of injury is responsible for 40% of all trauma mortality according to the American Association for the Surgery of Trauma. Intravenous (IV) Tranexamic Acid (TXA) has been used off-label to control traumatic hemorrhage for more than a decade. Unfortunately, the current formulation has an inherent deficiency, the IV form is not suitable for early administration and use (during the first 3 hours) when injuries that surpass first-responders training, capabilities and access occurs. During mass shootings, far/unsafe trauma environments and far-forward battlefields, this gap in treatment becomes self-evident and the early treatment (TXA treatment during the initial hour has greater impact on survival) is especially impacted. An easy to use, logistically friendly and portable Topical TXA, has the potential to provide local wound bleeding control with therapeutic serum levels similar to the IV formulation that will improve the service members and trauma victims survival. The goal of this collaborative effort lead by USUHS and carried out with multiple industry partners (private industry collaboration is lead by Lincoln Therapeutics, LLC.), is to develop an optimal Topical TXA formulation that can be applied at the scene of injury by anyone irrespective of their training. 

• Lead Researchers: Jong Lee, MD (jong.lee@usuhs.edu); Peter Bedocs, MD, PhD (peter.bedocs.ctr@usuhs.edu)