CINCINNATI–Neurotrauma experts at the University of Cincinnati Neuroscience Institute at University Hospital are seeking public input before launching federally funded research aimed at improving outcomes for patients who suffer traumatic brain injury (TBI).
The randomized clinical trial will assess whether administering the naturally occurring hormone progesterone in patients immediately after a moderate to severe traumatic brain injury will reduce brain damage and swelling and thereby improve the patients’ mental and physical outcomes.
The Cincinnati portion of the study will be led by Jay Johannigman, MD, associate professor and director of the division of trauma and critical care, and Lori Shutter, MD, associate professor of neurosurgery and neurology and director of the neurocritical care program.
“The nation is becoming increasingly aware of the devastation that traumatic brain injury can have on a person's life,” Shutter says. “Unfortunately, although there have been many efforts, we still do not have an effective treatment for a traumatic injury to the brain. The early information on progesterone for treatment of TBI renews our hopes that we may have something that can improve long-term outcomes.”
The progesterone study, funded by the National Institute of Neurological Disorders and Stroke, is known as ProTECT III, which stands for Progesterone for Traumatic Brain Injury–Experimental Clinical Treatment. The $14.5 million trial will enroll 1,140 patients over a period of three years at 17 medical centers throughout the United States. David Wright, MD, assistant professor of emergency medicine at Emory University in Atlanta, is the multicenter study’s lead investigator.
Public comment is required before the ProTECT study begins because a patient who has suffered a brain injury is unconscious and would not be able to give consent before doctors administer the treatment. In addition, a relative or guardian may not be immediately available to grant consent on the patient’s behalf.
Traumatic brain injury involves sudden damage to the brain caused by an outside force to the head, such as a car crash, a fall or a forceful blow from a heavy object. Roughly 1.5 million to 2 million adults and children suffer a traumatic brain injury in the United States each year. About 50,000 die and another 80,000 are permanently disabled, according to the Centers for Disease Control and Prevention. Traumatic brain injury is the leading cause of death and disability among people aged 1 to 44.
ProTECT III is the third phase of groundbreaking research into the effectiveness of progesterone, which is most commonly recognized as a female hormone but also has “protective” properties. Progesterone receptors are abundant in the brain, and laboratory research suggests that progesterone plays a role in the development of brain cells and in the protection of injured brain tissue.
Emory researchers concluded in an earlier pilot study involving 100 patients that giving progesterone to trauma victims shortly after a brain injury appeared to be safe and effective. Emory researchers also reported a 5 percent reduction in mortality among patients treated with progesterone as well as improved outcomes among patients with moderate injury.
Progesterone is an attractive therapy for several reasons, Shutter says. “It is FDA-approved; it can be administered quickly; it enters the brain quickly; and it is inexpensive.”
The current study, ProTECT III, involves patients aged 18 and over who have suffered a moderate to severe traumatic brain injury and who can begin treatment within four hours of their injury. A qualifying patient will be randomly assigned to one of two groups. One group will receive an IV mixture that contains progesterone (the study medicine). The other group will receive an IV mixture that has no progesterone (a placebo). The UC team expects to enroll approximately 100 patients over the three-year period at University Hospital.
Federal law established the "waiver of consent" in 1996 so that physicians could begin emergency treatment after any injury before obtaining consent from the patient or from a legal guardian or family member. Under terms of the ProTECT study, if a hospital is unable to reach a family member after 60 minutes of diligent effort, the emergency medicine team is allowed to enroll patients who meet the study's stringent criteria.
To qualify for the waiver, researchers must first explain the research to the community and gather feedback. UC researchers will discuss the ProTECT trial at community meetings during the next several months, with particular emphasis on demographic groups known to have a statistically elevated risk of severe traumatic brain injury. In addition, UC researchers must assess local residents' willingness for themselves or a family member to participate in this study. A complete description of the study can be reviewed at www.protectiii.com.
Those who review the study description will be invited to complete a short accompanying survey.
ProTECT III is a project of the Neurological Emergencies Treatment Trials (NETT), which was established by NIH in early 2007. NETT is a permanent research network that currently involves 17 university medical centers throughout the United States. UC’s involvement in NETT is overseen by Arthur Pancioli, MD, associate professor of emergency medicine and a member of UCNI.
Individuals who are opposed to being enrolled in a NETT study in the event that they were to suffer a neurological emergency can request an “opt out” bracelet by calling (513) 558-NETT (0095).
For more information about ProTECT, please contact Sara Stark at (513) 558-0095 or firstname.lastname@example.org. For more information about NETT, please visit http://nett.umich.edu/nett/welcome.