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DiaComp Funded Abstracts Collaborative Funding Program Funding Programs

Collaborative Funding Program Application Abstract
Predictive and diagnostic biomarkers for diabetic foot ulcers
Marjana Tomic-Canic   (Miami, FL)
The proposed work is uniquely aligned with DiaComp goals as it will advance collaborative studies on diabetic foot ulcers (DFU) a major diabetes-associated complication to identify predictive and diagnostic biomarkers. The goal of the project is to validate previously identified, specific, objective, quantitative tissue biomarkers that correlate with healing outcomes for DFUs. The proposed planning phase will allow optimization of the operational protocol for the future multi-center clinical trial. In a following large clinical trial, we propose to validate previously identified c-myc and ß-catenin as tissue biomarkers that can objectively and quantifiably distinguish healing from non-healing DFUs for both predictive and diagnostic purposes. Chronic non-healing DFUs are a prevalent, serious clinical problem with high rates of morbidity, disability and mortality, including a high risk for lower limb amputations. Ability to differentiate patients who will heal with standard care from patients who are at risk for DFU-associated complications and require early advanced therapy is critical to advancing wound care practice. This will allow targeted therapy and early intervention that will improve healing outcomes, reduce the risk for osteomyelitis, amputation and decrease costs of care. In a pilot study enrolling 25 patients with DFUs we found that increased nuclear presence of c-myc in DFU epidermis correlates with healing impairment. Nuclear ß-catenin shows similar trend. Therefore, the overall goal is to validate these two tissue protein markers, i.e. test if nuclear f c-myc and/or ß-catenin is correlated with objective quantitative measures of DFU wound closure in a multi-center clinical trial. We propose the planning phase that will establish and tests the functionality operational components required for clinical trial. Aim 1 will develop a Core Management Plan that will design and prepare the implementation and oversight of clinical, research and biostatistical aspects of large clinical trial for biomarker(s) validation. Aim 2 will perform a “test run” to implement standardization and logistics of the experimental approach on prospectively enrolled 10 patients with DFUs. We will utilize collaborative teams from Winthrop Hospital and University of Miami Wound Centers to evaluate shipment, quality assessment of debridement specimens and time to quantification (optimizing staining and quantification protocols). Added benefit from these samples will be to increase existing data set and prospectively confirm findings that c-myc % nuclear presence correlates with non-healing and can predict non-healing DFUs. It will also increase sample size to confirm if the trend of correlation of the ß-catenin to clinical outcomes indeed shows statistical significance. Successful completion of project will reform clinical care practices by providing the first validated, objective quantitative tissue biomarker(s) that can be used to: predict which DFUs are not likely to heal with current therapy and therefore require intervention; identify DFUs that have been surgically cleared of non-healing tissue and therefore are more likely to respond to biological therapies; and provide markers that can be used as determinants of success in future clinical trials.
Data for this report has not yet been released.