A randomized, double-blind Phase III clinical trial, involving approximately 1,140 patients over a three-to-six year period using the hormone progesterone to treat traumatic brain injury (TBI) will start in March 2010 at 17 medical centers across the USA. The National Institutes of Health (NIH) is funding the grant, which was awarded to Emory University.
Atlanta's Grady Memorial Hospital will serve as lead center, with faculty from Emory School of Medicine and Morehouse School of Medicine. David Wright, MD, associate professor of emergency medicine at Emory University School of Medicine will lead the clinical trial.
An earlier 3-year clinical trial involving 100 patients led the researchers to conclude that giving progesterone to trauma victims shortly after a brain injury appears to be safe and may reduce the risk of death and long-term disability. ProTECT I (Progesterone for Traumatic brain injury - Experimental Clinical Treatment) was the name of the first trial. The 2010 trial is called ProTECT III.
ProTECT I found evidence that progesterone is safe for use in patients suffering from traumatic brain injuries. The trial found that there was a 50% reduction in mortality among traumatic pain injury patients receiving progesterone treatment. Patients with moderate brain injury had reduced disabilities and improved functional outcomes, the scientists reported.
Progesterone exists naturally in limited but measurable amounts in the brains of males and females. Progesterone receptors exist in large quantities in human brain tissue. Studies suggest that progesterone is vital for the normal development of neurons in the brain and has a protective effect on damaged brain tissue.
Donald G. Stein, PhD, Asa G. Candler Professor of Emergency Medicine, Emory School of Medicine, and director of Emory's Department of Emergency Medicine Brain Research Laboratory, pioneered discoveries regarding the effect of progesterone following TBI - first discovering the neuro-protective properties of progesterone in the laboratory more than 25 years ago.
About 2 million American adults and children suffer from traumatic brain injury annually; 50,000 patients die and there are 80,000 new cases of long-term disability, according to the CDC (Centers for Disease Control and Prevention). Every 15 seconds one American man, woman or child sustains a significant traumatic brain injury. Scientists have not managed so far to identify effective medications to improve outcomes for such patients, despite the enormity of the problem.
Wright said "No new treatment for severe TBI has been approved in over 30 years. With such promising success in laboratory testing and in our previous clinical trial, we hope to conclude in this national trial that progesterone-along with standard medical trauma care-works better than standard medical care alone in reducing brain damage caused from a TBI."
Michael Frankel, MD, Emory professor of neurology, and Jeffrey Salomone, MD, Emory associate professor of surgery will be site principal investigators for the ProTECT III trial at Grady Memorial Hospital in Atlanta. The trial will be conducted through the Neurological Emergencies Treatment Trial (NETT) network coordinated by the University of Michigan. Data analysis will occur at the Medical University of South Carolina.
Exception from Informed Consent (EFIC) - as a large part of the drug's success is highly dependent on its prompt administration (as soon as possible after brain injury occurred), patients who are enrolled in the trial may be provided the progesterone hormone without consent of family members or next-of-kin.
Wright says that researchers usually get consent before a patient participates in a clinical study. If a person who sustained a traumatic brain injury is unconscious they will be unable to consent for themselves. In such cases permission will be sought from the patient's legal guardian, who is usually a next-of-kin. However, as prompt treatment is vital there may not be enough time to find and talk to somebody about the study before the medication is started.
Wright explained "In ProTECT III, a person might very well be enrolled in the study without a legal guardian's or family member's consent. The U.S. Food and Drug Administration (FDA) has, in fact, created a set of special rules, called "Exception from Informed Consent" (EFIC). These rules allow research studies in certain emergency situations to be conducted without consent."
EFIC applies only when all of the following apply:
- The person is in a life-threatening situation
- Current treatments are unproven or unsatisfactory
- The study might provide direct benefit to the person
- It is not possible to obtain informed consent from:
- the person because of his or her medical condition, or..
- the person's guardian because there is a very short amount of time required to treat the medical condition.
What is traumatic brain injury?Traumatic brain injury, also known as TBI or intracranial injury, is generally the result of a sudden, violent blow to the head. The brain is launched into a collision course with the inside of the skull, resulting in possible bruising of the brain, tearing of nerve fibers and bleeding.
TBI may also be caused by objects, such as bullets or a shattered piece of skull penetrating brain tissue. Causes of TBI may include falls, vehicle accidents, and violence.
TBI severity varies enormously, and depends on which part of the brain is affected, whether it occurred in a specific location or over a widespread area, as well as the extent of the damage. In mild cases the patient may experience only temporary confusion and headache. Serious TBI can be fatal.
A head injury usually refers to a traumatic brain injury, but is a broader category. Head injury may also involve damage to other structures (apart from the brain), such as the scalp or skull.
Source: Emory University
Written by Christian Nordqvist