Advancing Clinical Outcomes, Biomarkers, and Treatments for Severe TBI
Abstract
Severe traumatic brain injury (TBI) is a devastating condition for the affected individual and his/her family. Some patients recover full consciousness swiftly while others remain unconscious indefinitely, unable to communicate basic needs or participate in basic functional activities. Whether brief or prolonged, recovery from severe TBI involves complex, and potentially long-term, cognitive and physical impairments that interfere with patients abilities to perform daily tasks such as engaging in meaningful conversations. Yet there are few treatments available to improve recovery from severe TBI. One possible treatment option is repetitive transcranial magnetic stimulation (rTMS). Transcranial magnetic stimulation is a non-surgical method that uses magnetic fields to change the way specific regions of the brain function. Research suggests that rTMS can modulate brain activity in areas of the brain involved in arousal, attention, and language and may have the potential to restore these critical skills. A study currently funded by the U.S. Army Medical Research and Materiel Command is looking to determine whether rTMS can be used to improve functional skills for persons recovering from severe TBI. The purpose of this application is to further support the currently funded study by adding three supplemental projects. The purpose of the first project is to optimize subject enrollment for the currently funded study by supporting costs related to additional days each research participant should be hospitalized, the need for additional tests to monitor patient safety, and the need to support standard of care for some patients. The purpose of the second project is to advance TBI clinical assessments so that we can accurately determine if patients have improved as a result of treatment. The second project aims to (1) determine how well five TBI outcome assessments do or do not measure the same kinds of neurobehavioral function; (2) increase accuracy of TBI outcome assessments by neutralizing influence of rater severity and leniency; and (3) identify meaningful amounts of change in function so that clinicians and researchers can select TBI outcome assessments that are best suited to the patients being treated and that support future TBI clinical trials. The purpose of the third project is to identify specific microRNA (miRNA), referred to as biomarkers. These biomarkers are small molecules that fine-tune the expression of genes that can result when brain cells are recovering from injury. In this study, we will identify changes in these biomarkers in three situations: (1) as a result of having a severe TBI; (2) having severe TBI and receiving rTMS treatment; and (3) in patients who recover whether or not they received rTMS treatment. These biomarkers could help identify patients with severe TBI more quickly and also help with evaluating the effectiveness of future therapeutic interventions. The aims of this third project are to: (1) identify miRNAs associated with severe TBI and with rTMS treatment; (2) determine how much severe TBI-associated miRNA are altered by rTMS treatment; and (3) determine how much changes in levels of miRNA are associated with change in neurobehavioral functioning for patients who did not get the rTMS treatment. The currently funded study, combined with the three supplemental projects, will provide an advanced understanding of true neurobehavioral effects of rTMS treatment specifically but will also apply to TBI clinical trials in general. The studies will also tell us more about how the underlying neurobiology of the brain may be altered as a result of rTMS treatment. Identifying miRNA biomarkers will help better describe the severity of TBI as well as point to those patients who might most favorably respond to rTMS treatment. These findings have application to many military Service members who may face the devastating consequences of severe TBI during military service.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1620023
Entities
People
- Theresa Pape
Organizations
- Chicago Association for Research and Education in Science
- United States Army