Abstract 295: The Stem Cell Therapy to Prevent Expansion of Abdominal Aortic Aneurysm (STOP-AAA) Trial: Rationale and Design

Abstract

Background: Abdominal aortic aneurysm (AAA) is the 13 th leading cause of death in the United States. The only options for treatment at present for AAA are open surgical and endovascular repair, both of which are associated with significant morbidity, mortality, and expense.Thus AAA represents an unmet medical need. AAA pathogenesis is a multifactorial inflammatory process characterized by activation of T-cells,macrophages and neutrophils resulting in degradation of the aortic wall. Mesenchymal stromal cells (MSCs) suppress T-cell and macrophage activation, inhibit matrix metalloproteinases and have been shown to decrease aneurysm expansion in murine models. Methods: The STOP-AAA trial, from the NHLBI funded Cardiovascular Cell Therapy Research Network, is a randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of autologous bone marrow derived MSCs in suppressing expansion of small AAA (35-50mm).Forty patients will be randomized in a 1:1 fashion to receive systemic administration of placebo or 3 doses of 2x10 6 MSC/kg. at baseline, 24, and 52 weeks. The primary endpoint will be change in AAA diameter at 18 months as measured by a single blinded observer using contrast enhanced helical computed tomographic angiography (CTA).The secondary endpoints include time to elective repair, incidence of AAA related deaths and rupture,change in aortic mural inflammation at 18 months as quantified by F18-fluorodeoxyglucose (FDG) uptake with integrated positron emission tomography and computed tomography (PET/CT), changes in circulating mRNA, microRNA, and inflammatory cell profiles, changes in serum cytokine levels, and major adverse cardiac events. Conclusion: The STOP-AAA will be the first in man study to assess the efficacy of autologous bone marrow derived MSCs to suppress AAA expansion. Furthermore the data collected from this novel trial will provide unique mechanistic insights in the immunomodulatory properties of this stem cell population.