UCSF neurosurgeons at San Francisco General Hospital Medical Center are planning a unique clinical study to see if lowering the body temperature of patients with severe traumatic brain injury (TBI) will help improve their condition - but first the neurosurgeons need to reach the local public, in part through the media.
Because the study, which will be conducted at nine institutions nationwide, will require treating patients, all of whom are unconscious, within four hours of their injury, the window of opportunity for getting consent for the treatment from the legal guardian, family members or registered domestic partner will be limited. Given the time-sensitivity, the researchers will rely upon a “waiver of consent” policy, which, under a federal law established in 1996, allows physicians to begin emergency experimental treatment aimed at improving the outcome of patients before gaining consent from family members.
Under the terms established for the trial, if the hospital is unsuccessful in reaching family members after 90 minutes of diligent effort, the neurosurgical team will be allowed to enroll patients who meet the very stringent criteria established for the study. If family members or a significant other are reached subsequently and oppose the treatment, the patient who was cooled will be rewarmed. All patients will also receive the standard care for a severe traumatic brain injury.
Severe traumatic brain injury is one of the leading causes of death in persons between the ages one and forty-five. “Statistics show there is a head injury every 15 seconds in this country, and every five minutes someone is killed or permanently disabled due to head injuries. Better techniques for treating these patients are desperately needed,” says Geoffrey Manley, MD, PhD, Chief of Neurotrauma at San Francisco General Hospital Medical Center, UCSF assistant adjunct professor of neurological surgery and a co-principal investigator of the trial.
In keeping with the regulations of the waived consent policy, the participating institutions must make a substantial effort to inform the local public about the trial in the months prior to its implementation. This step is intended to determine if there is community support for the trial, which is scheduled to begin this fall.
To this end, the UCSF-SFGH Medical Center neurosurgical team is holding approximately 12 community meetings with groups who represent populations living in the region that the SFGH Trauma Center serves (The City of SF and Northern San Mateo County), as well as those groups that represent people most at risk for severe traumatic brain injury, which is primarily caused by accidents and assaults. So far, the support has been strong for the trial, says Michele Meeker, RN, UCSF neurosurgical clinical research nurse at SFGH Medical Center and the study coordinator.
The neurosurgical team is also seeking help from the media in educating the public about the proposed plan. “We want the members of the community we treat to have every opportunity to learn about this trial and to comment on it,” says Manley.
Common causes of brain injury are accidents involving cars, motorcycles, skateboards, scooters, bicycles and pedestrians, as well as incidents occurring at construction sites. The risk for severe TBI is twice as high for males and disproportionately affects adolescents, young adults and the elderly. Currently, 30 percent to 40 percent of patients die from severe TBI, and a high percentage result in a vegetative state or have a severe long-term disability.
In recent years, neurosurgeons have observed that in patients with severe brain trauma, a drop in body temperature to a low level, a condition known as hypothermia, at times appears to reduce the extent of long-term injury to the brain.
Results of a large national clinical trial of body cooling for brain trauma patients, reported in The New England Journal of Medicine (Feb. 22, 2001), indicated that the cooling technique was helpful for patients between the ages of 16-45. In this subgroup, 24 percent of the patients who underwent body cooling down to 33 degrees Celsius (91.4 Fahrenheit) had a better than expected outcome, either experiencing a good recovery or only a moderate disability.
Patients and their families were contacted three and six months after their injury to determine the level of recovery.
While scientists cannot yet explain the improvement caused by cooling, they expect that the lower temperature stabilizes the blood vessels and inhibits the release of certain brain chemical messengers that initiate secondary damaging events for patients, says Martin C. Holland, MD, Director of Neurosurgery at San Francisco General Hospital Medical Center, UCSF assistant clinical professor of neurological surgery and a co-principal investigator of the UCSF study.
The current study, which is funded by the National Institutes of Health, will focus exclusively on patients with severe traumatic brain injury in the 16-45 year old age group. The trial is expected to enroll 220 patients nationwide and to take place over three to four years. SFGH Medical Center expects to enroll at least eight patients per year. The trial is a phase II trial, designed to see if the treatment is safe and effective. It is being led by University of Texas-Houston, Houston Medical Center, which also led the earlier trial.
The study will be “randomized,” meaning that patients will be included in the study on a random basis, as determined by a centralized computer system set up for the national trial. All patients will receive the standard treatment for severe traumatic brain injury, but only half will undergo the cooling process. Once the neurosurgical team has determined that a patient meets the rigorous criteria for participation, the team will call an automated telephone line that will notify them whether or not the new patient will undergo the hypothermia experiment.
Once a patient has been enrolled, he or she will be cooled with a specially designed cooling suit for 48 hours, starting within four hours of the injury. To determine whether the treatment was successful, the patient will be tested by an independent evaluator at intervals of three, six and 12 months after injury.
Attention media: For more information about this trial, please contact Jennifer O’Brien, in the UCSF News Office (415/476-2557).
Members of the public may contact the coordinator of the planned UCSF-SFGH clinical trial, Michelle Meeker, RN, 415/206-3220, or [email protected]