Redox Trapping for Biospecimen Preservation and Innovation in Sepsis Care

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ABSTRACT We aim to advance sepsis research and clinical diagnosis by introducing a new redox trapping formulation for preservation of blood specimens. The new formulation is anticipated: 1) to prevent artifactual oxidation and loss of specimen integrity during storage, 2) to enable studies of redox metabolism which underlines the dysregulated immunometabolic response in sepsis, and 3) to improve analysis of differentiating redox molecular markers associated with demographic features (age, gender and racial ethnicity). Our combined expertise of redox biochemistry and innovation in patented redox chemical reagents, sepsis mechanisms, trial design and clinical expertise will be applied first to validate the new redox trapping formulation (R21 Phase) and then to scale-up by deploying this for collection of blood specimens at sites participating in the EMbedded Precision in Acute Care Trials (EMPACT) Network (R33 Phase). This is a newly formed network of premier critical care clinical trials sites designed to conduct precision clinical trials and discovery research in sepsis. Successful accomplishment of our aims will improve staging of septic patients and clinical precision research for discovery of new therapeutic targets for treatment of sepsis. More specifically, during the R21 Phase we will investigate the compatibility of the new redox formulation with high-end mass spectrometry and single cell technologies to evaluate its performance for measurement of redox and other biomarkers. The new formulation will be compared with current standard of care procedures for blood collection for clinical and research purposes (gold standard). To further validate this formula in sepsis patients, we will then evaluate its effects on standard clinical lab tests in a pilot study using prospectively collected paired single timepoint samples from critically ill patients with sepsis. We will further determine the advantage of redox trapping formulation by linking the measurements to physiologic and outcome data collected passively through the Wake Forest Critical Care Data Analytic Platform. Upon accomplishment of key metrics at the completion of R21 Phase, we will work with the EMPACT Network in the R33 Phase to collect blood specimens from 150 patients at 3 timepoints across the continuum of their disease progression using the standard methods and the new redox formulation. Analysis using high-end omics technologies will produce information-rich and redox-specific datasets, which will be integrated using bioinformatics approaches and linked to clinical data captured passively via the EMPACT data warehouse to generate new hypotheses for sepsis research. Lastly, we include a plan to share cryopreserved specimens, clinical and molecular data with investigators at the institution to support discovery or hypothesis-driven research through pilot mechanisms under the Center for Redox Biology and Medicine and Critical Illness, Injury and Research Recovery Research Center directed by MPIs Furdui and Files, respectively, and with outside investigators via EMPACT.