CONTACT: JENNIFER CRONIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-9917; fax (319) 335-8034
Release: Sept. 9, 1999
UI receives $8.1 million NIH grant
IOWA CITY, Iowa -- The University of Iowa has received
an $8.1 million grant from the National Institutes of Health to oversee a
multi-site trial testing the use of hypothermia as a way to improve neurologic
outcomes in patients needing a certain common brain operation.
"This trial is an exciting prospect," said Michael
Todd, M.D., UI professor of anesthesia and the project's principal investigator.
"If successful, it will almost certainly benefit other areas of medicine in
which brain protection is needed."
The trial, which will involve 25 to 30 sites around
the United States and the world, will focus on improving the treatment of
a sometimes-fatal condition called a subarachoid hemorrhage. The problem,
usually caused by a ruptured intracranial aneurysm, involves blood vessels
near the base of the brain that leak and fill the surrounding cavity with
blood. The condition affects roughly 30,000 people annually in the United
States and Canada alone, said Todd, who put the worldwide figures at several
hundreds of thousands.
A third of those with such hemorrhages die instantly
or never recover from complications. For the remaining patients, treatment
has typically involved the neurosurgical placement of a clothespin-like clip
around the aneurysm to prevent another, even more devastating episode of bleeding.
However, since surgery is often urgent and because the brain may already be
damaged from the original hemorrhage, about 25 percent of the patients wake
up from surgery with stroke or some other additional neurological condition.
Although other treatments for such aneurysms are being explored and used,
such surgery is still quite common.
"Most people accept the risk of stroke or other neurological
injury as a reasonable trade-off," Todd said. "But they may not have to if
the trial shows that hypothermia works."
During the next five years, researchers hope to enroll
1,000 patients in the trial. After determining whether someone is eligible,
researchers will randomly assign the patient to one of two groups. For the
control group, researchers will keep the patients' body temperatures at the
normal level of 37 degrees Celsius (98.6 degrees Fahrenheit). For the other
group, researchers will drop the body temperature to 33 degree Celsius (91.4
degrees Fahrenheit). The patients will remain at the lower temperature until
just after the surgeon clips the aneurysm. For three months following surgery,
the researchers will monitor patients in each group for any neurological impairment
and for their ability to perform routine activities of daily living.
Previous research and Todd's pilot study suggest that
there is a strong possibility that hypothermia might prevent neurological
problems. However, the reason why is unclear. The traditional view that many
hypothermia advocates have argued is that cooling the body simply slows down
the brain's metabolism and enables it to better tolerate the jarring and other
hits it takes during surgery.
"The reason why hypothermia might prevent neurological
problems is probably much more complicated than that," Todd said.
Cooling an individual in the operating room does have
risks. In other operations, there have been increased rates of heart attacks,
surgical wound infections and problems with the blood not clotting normally,
"We think that those risks are very low for what we
are proposing," he said. "In fact, in a pilot study, we didn't see any of
those problems occur."
Todd and his colleagues have been working on the project,
which included a pilot study, since 1991.
About 20 UI researchers will work on the five-year
trial. The UI is the coordinating center and will manage the 25 to 30 centers
involved -- including sites in Australia, Canada, England, Austria and, likely,
Coordinating the multi-site trial involves faculty
in several departments within the College of Medicine and the new College
of Public Health. Other College of Medicine faculty involved, in addition
to Todd, include: Bradley Hindman, M.D., associate professor of anesthesia;
Patricia Davis, M.D., professor of neurology; Daniel Tranel, Ph.D., professor
of neurology; Steven Anderson, Ph.D., assistant professor of neurology; and
Matthew Howard III, M.D., associate professor of neurosurgery. Harold Adams,
M.D., professor of neurology, will serve as patient safety monitor.
The College of Public Health group will be directed
by Robert Woolson, Ph.D., UI professor and head of biostatistics, and includes
William Clarke, Ph.D., UI professor and head of the UI Clinical Trials Statistical
and Data Management Center, who will oversee the trial's data collection;
and Jim Torner, Ph.D., professor and head of epidemiology. At least 10 other
UI staff members will also be involved.
"It really is an enormous collaborative effort," Todd
said. "Winning this grant wouldn't have happened without all these people
pulling it together. It is a unique trial because it requires the collaboration
of at least four different medical specialties: anesthesiology, neurosurgery,
neurology and public health. Most trials just involve one particular department.