Office of Naval Research Awards VCURES Grant to Examine the Role of Androstenetriol in Reducing Mortality from Traumatic Shock

The U.S. Office of Naval Research’s Casualty Care and Management Program has awarded VCURES a three year $430,000 grant to study the use of androstenetriol for the treatment of traumatic shock. Androstenetriol is an immunosteroid and derivative of dehydroepiandrosterone developed by Dr. Roger Loria at VCU and licensed to Hollis Eden, Inc. (http://www.holliseden.com/index.cfm). The study is entitled: Preliminary Studies on the Effects of Androstenetriol Induced Immunomodulation in the Treatment of Traumatic Shock.

Participants in the study include:

Roger Loria, PhD: Principal Investigator: Senior VCURES Investigator. Professor of Microbiology and Immunology and Emergency Medicine. Senior VCURES Investigator

R. Wayne Barbee, PhD: Co-Principal Investigator: Senior VCURES Investigator. Assistant Professor of Emergency Medicine and Physiology. Associate Director of Research VCU Department of Emergency Medicine

Kevin R. Ward, MD: Co-Investigator: Associate Director of VCURES. Assistant Professor of Emergency Medicine and Physiology. Director of Research VCU Department of Emergency Medicine

Ramana Feeser, MD: Co-Investigator: VCURES Investigator: Assistant Professor o Emergency Medicine. VCU Department of Emergency Medicine

Rao Ivatury, MD: Co-Investigator: Associate Director of VCURES. Professor of Surgery, Emergency Medicine, and Physiology. Chairman Division of Trauma and Surgical Critical Care and Emergency Surgery VCU Department of Surgery

The three specific goals of the preclinical research in models of traumatic shock will be to examine the ability of androstenetriol to (1) modulate the immune and inflammatory response systemically and in multiple organ systems, (2) preserve microcirculatory flow and tissue oxygenation and (3) improve survival. Suppression of the immune system following traumatic shock is a major factor contributing to the development of infection. These inflammatory or infectious complications have been estimated to be responsible for as much as 60% of deaths from trauma in the civilian population. This high mortality rate after trauma highlights the importance of mediating the relationship between stress response and immune suppression.

Previous preclinical work by Dr. Loria’s laboratory has suggested that immune regulating hormones such as androstenetriol may confer protection against a wide range of infectious agents by modulating immune function. These studies have also demonstrated that androstenetriol is particularly effective when stress is a complicating factor in the injury. This grant will allow researchers to evaluate the ability of androstenetriol to reduce mortality and improve immune function after traumatic injury. The primary objective of this research for the military is to determine if androstenetriol might be beneficial if given with initial resuscitation fluids to prevent immune dysfunction that is associated with later development of infections and death following trauma in the battlefield.

“We have reported that immune regulating hormones offer a potential weapon against conditions associated with immune suppression and dysregulation resulting from trauma, hemorrhage and sepsis,” said Dr. Loria. “A reduction in mortality with androstenetriol in this model system of traumatic hemorrhagic shock would justify clinical trials in traumatic shock.”
“It is now appreciated that trauma may result in early and protracted suppression of the host immune response,” stated Dr. Ward. “This suppression, although not affecting immediate survival, is believed to be a major factor portending the development of post-resuscitation complications such as sepsis, multisystem organ failure and death, which have a multimodal distribution of occurrence after the initial insult. The relationship and link between post-traumatic immune dysfunction and microcirculatory tissue oxygenation on a whole body basis has not been studied extensively, and enhancing tissue oxygenation by modulating the immune system may be key in improving survival.”

“Previously, we have been very limited in what could be offered in the ‘golden hour’ of care that would produce long-term benefits during the days to weeks of recovery following the initial injury,” stated Dr. Ivatury, who is also the current president of the Pan American Trauma Society. “In terms of military operations, the paradigm is even more complex, since wounded soldiers and their caregivers really do not have a ‘golden hour’ in which to work.”

This study utilizes a unique model of injury and treatment that is intended to mimic as closely as possible both the injury and treatments provided in traumatic shock. “A shortcoming of many preclincial studies of new treatments for shock that have shown promise but have later failed in clinical studies is that these preclinical studies have not taken into account very important factors of the injury as well as treatments, both of which can have a profound effect on the immune system,” said Dr. Barbee.

This project is a part of the VCURES Operation Purple Heart Program which focuses on combat casualty care research. For more information please see: http://www.vcu.edu/vcures/purpleheart.htm or contact VCURES.