Nationwide Childrens Hospital Clinical Trial to Use Drug to Boost Immune System Function in Critically Injured Children, May Prevent Infection

October 11, 2011

Thanks to funding from the National Institutes of Health, Nationwide Children’s Hospital will test the ability of a drug commonly used to improve immune function in pediatric cancer patients to help prevent hospital-acquired infection after severe trauma. It will be the first clinical trial aimed at improving immune function in critically injured children.

Traumatic injury remains the leading cause of death for children outside the neonatal period. Beyond the life-threatening damage caused by initial injury, traumatically injured children are at high risk of developing life-threatening nosocomial infection, also known as hospital-acquired infection. The incidence of nosocomial infection is especially high in injured children who require treatment in the intensive care unit.

“Adult studies have shown that innate immune function, which is responsible for protecting the body by identifying and killing pathogens, is impaired following critical injury,” said Mark Hall, MD, Critical Care Medicine physician and principal investigator in the Center for Perinatal Research both at Nationwide Children’s Hospital. “Using a unique immune surveillance approach at Nationwide Children’s, we have shown a similar finding in children and are able to tell, in a matter of hours, whether or not a child is at high-risk for developing nosocomial infection.”

Dr. Hall’s studies have identified specific thresholds of immune function, by measuring the ability of patients’ blood to produce certain chemicals when stimulated outside the body that predict infection risk.

“Thanks to our studies, we have known for some time what level of immune function is associated with poor outcomes,” said Dr. Hall, also a faculty member at The Ohio State University College of Medicine. “What has been missing is a possible intervention.”

With funding from the National Institute of General Medical Sciences, Dr. Hall is set to lead a clinical trial to help determine whether GM-CSF, a drug commonly used to reconstitute bone marrow in leukemia and bone marrow transplant patients, could be the intervention needed to help protect critically ill children from infection.

“Several small studies in adults suggest that GM-CSF can reverse critical-illness-induced immune suppression,” said Dr. Hall. “Ours is the first study to use this drug in critically injured children.”

Through the GIFT (GM-CSF for Immunomodulation Following Trauma) study, Dr. Hall will test whether GM-CSF can boost the immune system enough to reduce the risk for nosocomial infection after critical injury in high-risk children. After determining the lowest tolerable, yet effective dose, Dr. Hall’s team will test whether GM-CSF delivery can prevent nosocomial infection in children whose immune monitoring data designates them at high risk for infection. They will also perform a smaller version of this study in high-risk children who have severe traumatic brain injury.

“We anticipate that the GIFT study will represent a paradigm shift in the management of pediatric trauma in that it will demonstrate the role of immune stimulation in reducing infection risk in this important, understudied group of children,” said Dr. Hall.

About Nationwide Children's Hospital

Named to the Top 10 Honor Roll on U.S. News & World Report ‘s 2018-19 list of “Best Children’s Hospitals,” Nationwide Children’s Hospital is one of America’s largest not-for-profit freestanding pediatric health care systems providing wellness, preventive, diagnostic, treatment and rehabilitative care for infants, children and adolescents, as well as adult patients with congenital disease. Nationwide Children’s has a staff of more than 13,000 providing state-of-the-art pediatric care during more than 1.4 million patient visits annually. As home to the Department of Pediatrics of The Ohio State University College of Medicine, Nationwide Children’s physicians train the next generation of pediatricians and pediatric specialists. The Research Institute at Nationwide Children’s Hospital is one of the Top 10 National Institutes of Health-funded freestanding pediatric research facilities. More information is available at NationwideChildrens.org.