UT Southwestern Medical Center researchers are conducting two pilot clinical trials to determine whether a single, early dose of estrogen can improve survival and neurological outcomes after severe traumatic brain injury or traumatic hemorrhagic shock.
In these double-blind studies, male patients transported to Parkland Memorial Hospital following severe traumatic brain injury or severe blood loss associated with a traumatic injury will be assigned randomly to receive either Premarin (estrogen) or a placebo intravenously after arriving in the emergency department.
Estrogen or a placebo will be administered as a single-dose within two hours of injury. The researchers will measure biomarkers of injury and repair in different body fluids during the first few days after injury, and also will evaluate survival and neurological outcomes.
Despite advances in surgical interventions and intensive care management, about 35 percent of patients with severe traumatic brain injury and hemorrhagic shock die. Many survivors do not fully recover and are left with permanent disability.
"Following traumatic brain injury or hemorrhagic shock, secondary injury, such as inflammation, begins rapidly and greatly worsens the initial injury," said Dr. Jane Wigginton, assistant professor of emergency medicine at UT Southwestern and the trials' principal investigator. "Hundreds of animal studies have shown that estrogen significantly reduces secondary injury. Those studies give us hope that this new therapy offers considerable promise and minimal risk following one dose in patients with life-threatening traumatic injuries."
Dr. James Simpkins, chair of pharmacology and neuroscience at the University of North Texas Health Science Center at Fort Worth, initially discovered in 1994 in animals that estrogens protect brains from damage.
"There are now several hundred high-quality animal studies demonstrating the effectiveness of estrogens in protecting the brain from the damaging effects of traumatic brain injury, stroke, hemorrhagic shock and chemical injury," said Dr. Simpkins. "These trials will be the first ever critical assessment of the effects of rapid intervention with estrogen on the outcome of traumatic brain injury in a human population."
Intravenous estrogen has been used safely for decades in both men and women to treat excessive bleeding of the uterus and prostate cancer. While animal studies have found that estrogen reduces inflammation and minimizes secondary injury, the effects of estrogen have not been tested in patients with traumatic brain injury and severe bleeding after a traumatic event.
Dr. Wigginton said for this study, only men are being given a dose of estrogen; 70 percent of trauma patients with severe brain injury or blood loss are young males. Limiting the study to men, who represent the most frequently affected population, also will remove the confounders of potentially high estrogen levels that might occur naturally in women, or be caused by birth control pills or hormone replacement therapy.
Because patients will be critically ill and the drug needs to be given rapidly following trauma, they will not be able to give informed consent for the study. Area residents who want to be excluded can opt out by calling 214-648-6726. Those individuals will be given a special wristband to alert doctors in the emergency department that they don't want to participate in the study. Researchers anticipate enrolling 50 patients in each study.
"We are highly enthusiastic about the evaluation of estrogen as an acute treatment in patients with traumatic brain injury and severe blood loss, given the significant benefit demonstrated in animal studies and safety data in humans prescribed intravenous estrogen for other indications," said Dr. Ahamed Idris, professor of emergency medicine at UT Southwestern. "It is our greatest hope that these groundbreaking studies will soon translate into improved survival and neurological outcomes in trauma patients around the world."