A multi-center clinical trial is underway to evaluate repurposed drugs for the treatment of traumatic brain injury (TBI), a condition affecting millions and resulting in approximately 70,000 deaths annually in the United States. The study, led by UC San Francisco (UCSF) and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Network, aims to address the significant lack of effective treatments for TBI despite decades of research.
The trial utilizes an adaptive platform design to simultaneously test multiple drugs already on the market for other conditions, such as blood pressure, infection, and high cholesterol. These drugs have shown preliminary promise in small TBI studies. The trial is enrolling participants with moderate to mild TBI, including concussion, across 18 Level 1 trauma centers nationwide.
Innovative Adaptive Platform
Principal investigator Dr. Geoffrey Manley, professor of neurosurgery at UCSF and chief of neurosurgery at Zuckerberg San Francisco General Hospital, emphasized the advantages of the adaptive platform. "While most clinical trials test one treatment at a time, we are using an adaptive platform that allows us to test three drugs at the same time," he stated. This approach increases a participant's chance of receiving an active drug (75% vs. 50% in traditional trials) and allows for the addition of new therapies and the discontinuation of ineffective ones as the trial progresses.
The trial is supported by an agreement with the Department of Defense, U.S. Army Medical Materiel Development Activity (USAMMDA), reflecting the military's interest in TBI research due to the high incidence of TBI among service members, with over 300,000 cases stemming from conflicts in Afghanistan and Iraq.
Biomarker-Driven Patient Selection
One of the critical aspects of this trial is the use of biomarkers and advanced imaging to improve patient selection and monitoring. Previous TRACK-TBI studies have identified protein biomarkers in blood that can indicate TBI even when CT scans appear normal, and can predict mortality and severe disability. Additionally, CT scan patterns have been linked to recovery outcomes. These findings are being used to identify appropriate trial participants and track their progress.
Enrollment and Study Design
Participants must enroll on the day of their injury and have a CT scan showing evidence of bleeding, along with blood tests and examinations indicating moderate to mild TBI. The trial aims to enroll 672 participants over the next four years. The first four participants were enrolled at UCSF in August, with other TRACK-TBI Network sites preparing to begin enrollment.
Addressing Unmet Needs
Dr. Manley also highlighted the lack of public awareness and patient advocacy in the TBI space. "One of the barriers in treatment development has been a relative absence of public awareness about TBI. It’s an area that lacks patient-led advocacy," he said. He expressed hope that this trial will lead to effective treatments and foster future collaborations with pharmaceutical companies.
