Saliva biomarkers for predicting outcome in pediatric and adult patients with severe and moderate TBI Traumatic brain injury (TBI) is a leading cause of mortality and morbidity around the world, with increasing incidence. In the US, TBI is a contributing factor to 30% of all injury-related deaths. Patient with more severe TBI injuries (sTBI) are more likely to require hospitalization and suffer long-term disability. There is unmet need for diagnostic and prognostic biomarkers to aid in treatment decisions and outcome prediction in sTBI patients. The ultimate goal of this SBIR project is to validate saliva biomarkers for noninvasive prognostics of severe and moderate TBI, and translate the biomarkers into a commercial test. The proposed Phase I will show feasibility of the core technology: saliva biomarkers that accurately predict neurological outcome at 6 months after moderate to severe TBI, in pediatric and adult patients. Preliminary studies (N=91): Saliva samples were collected at 24h after sTBI (GCS 3-8, N=30, age 16-73). N=8 candidate markers were identified based on correlation with poor neurological outcome at 6m after injury (Glasgow Outcome Scale-Extended score, GOSE 1-3), and diagnostic accuracy for acute sTBI. Controls (N=40, age 7-77, ED patients without TBI and healthy volunteers) showed specificity of the markers for TBI, and potential to translate the technology for children. The proposed study will extend the feasibility of saliva biomarkers across age and TBI severity.
Specific Aim 1 Adult and pediatric TBI patients (N=70, 1month to 75 years of age, GCS score 3-12) and controls (N=60, orthopedic injury and healthy) will be studied at University of Pittsburgh Medical Center and Children's National Medical Center. N=360 saliva samples will be collected at 24h, 48h, 72h after TBI and at enrolment from controls. Neurological outcome will be assessed using GOSE at 6m after TBI and OI. The proposed sample size will provide >80% statistical power to validate biomarkers in patients stratified by outcome, age and sex. Primary outcome: poor neurological outcome at 6m after TBI (GOSE 1-3). Secondary outcome: mortality at discharge or 6m after TBI.
Specific Aim 2 will measure N=8 candidate markers in saliva samples from SA1 using 2 previously validated laboratory immunoassays. ROC analysis will determine prognostic accuracy of individual markers for TBI outcome and diagnostic accuracy for acute TBI. Logistic regression at 95% CI will show how accurately the markers predict 6 month-neurological outcome at 24h, 48h and 72h after TBI. Expected Outcomes: This project will demonstrate feasibility of saliva markers for noninvasive TBI prognostics. Representative and large sample size (130 patients across age, sex and geography) will provide statistically significant, generalizable clinical data. Orthogonal assays will provide cross-validated data. Demonstration of technical feasibility in SA2 will provide GO criteria for a full marker validation and device prototyping in Phase II. If successful, the project has potential for high impact by providing new biomarkers for noninvasive TBI diagnostics and prognostics, and advancing TBI therapies. The proposed saliva TBI test has a strong commercial potential based on limited competition and existing team of proven industry partners.
Saliva biomarkers for predicting outcome in pediatric and adult patients with severe and moderate TBI Traumatic brain injury (TBI) is a leading cause of disability and death. However, there is no objective test to diagnose TBI and predict recovery. The ultimate goal of this SBIR project is to develop a rapid saliva test for noninvasive diagnostics and prognostics of TBI in children and adults.
