Principle Investigator: Charles S. Cox, MD
Organization: University of Texas Health Science Center at Houston
Trauma is the leading cause of death among individuals aged 1–44 and ranks third in overall mortality in the U.S., claiming around 180,000 lives annually; up to 20% of these deaths are potentially preventable. Approximately 75% of traumatic deaths occur within the first 3 days post-injury, primarily due to uncontrolled bleeding and traumatic brain injuries (TBI). Beyond 3 days, the remaining 25% of deaths occur gradually from conditions linked to the initial tissue injury, shock, and resuscitation. Acute kidney injury (AKI) is when there is an abrupt decline in kidney function that takes place over hours to days after injury. Up to 50% of trauma and burn patients will experience AKI and with it associated prolonged hospital stays, increased complications, and possible death.
To date there are few if any effective treatments for trauma- and burn-associated AKI aside from supportive care and dialysis. This is an area of unmet medical need. Cellular therapies, specifically mesenchymal stem cell (MSC) therapies, offer promise for treating AKI as they target multiple therapeutic avenues that current approaches do not, including preventing further cell damage and inflammation as well as triggering self-regeneration and reparative processes.
Our project seeks to explore the safety and therapeutic potential of multi-dose, adipose tissue-derived MSCs for treating AKI in trauma and burn patients. We hypothesize that 3 doses of MSCs daily for 3 days will be safe and effective for treating AKI. We will also investigate systemic biomarkers in AKI and how they change with MSC treatment. We will do so via a Phase 1/2a randomized, double-blind, placebo-controlled clinical trial at 3 sites. In the first group of patients (10 patients), all patients will receive MSC infusion, and the safety of the infusion will be evaluated. In the second group of patients (60 patients, 30/treatment), patients will be randomized 1:1 to receive either 3 intravenous infusions of MSCs every 48 hours in 3 doses or placebo. Treatment will occur over 96 hours, and patients will be followed for 1 year. Blood and urine samples will also be collected to evaluate systemic biomarkers in AKI and their response to treatment.
While great advances have been made in the treatment of injured and bleeding patients for bleeding control and resuscitation, few treatments have been developed that improve outcomes of patients who survive initial injury and are then admitted to intensive care, including for AKI. Current paradigms of prolonged evacuation time in current military care will result in more severely ill patients arriving alive into intensive care, who will ultimately suffer AKI. Additionally, as these patients consume large amounts of resources, and there are inherently limited resources and personnel in far-forward settings, patients with AKI will complicate care. Treatment with MSCs has the potential to decrease the duration and intensity of AKI that occurs in trauma and burn patients in these scenarios. Success will involve not only facilitated field care and improved outcomes in military settings but also better outcomes in civilian trauma and burn patients.