S Keisin Wang1, Linden A Green1, Ashley R Gutwein1, Natalie A Drucker1, Raghu L Motaganahalli1, Andres Fajardo1, Clifford M Babbey1, Michael P Murphy2. 1. Division of Vascular Surgery, Department of Surgery, IU Health Center for Aortic Disease, Indiana University School of Medicine, Indianapolis, IN; VA Center for Molecular and Cellular Therapeutics in Cardiovascular Disease, Richard L. Roudebush VA Medical Center, Indianapolis, IN. 2. Division of Vascular Surgery, Department of Surgery, IU Health Center for Aortic Disease, Indiana University School of Medicine, Indianapolis, IN; VA Center for Molecular and Cellular Therapeutics in Cardiovascular Disease, Richard L. Roudebush VA Medical Center, Indianapolis, IN. Electronic address: mipmurph@iupui.edu.
Abstract
BACKGROUND: Abdominal aortic aneurysms (AAAs) are a major source of morbidity and mortality despite continuing advances in surgical technique and care. Although the inciting factors for AAA development continue to be elusive, accumulating evidence suggests a significant periaortic inflammatory response leading to degradation and dilation of the aortic wall. Previous human trials have demonstrated safety and efficacy of mesenchymal stem cells (MSCs) in the treatment of inflammation-related pathologies such as rheumatoid arthritis, graft versus host disease, and transplant rejection. Therefore, herein, we describe the Aortic Aneurysm Repression with Mesenchymal Stem Cells (ARREST) trial, a phase I investigation into the safety of MSC infusion for patients with small AAA and the cells' effects on modulation of AAA-related inflammation. METHODS: ARREST is a phase I, single-center, double-blind, randomized controlled trial (RCT) investigating infusion both dilute and concentrated MSCs compared to placebo in 36 small AAA (35-45 mm) patients. Subjects will be followed by study personnel for 12 months to ascertain incidence of adverse events, immune cell phenotype expression, peripheral cytokine profile, and periaortic inflammation. Maximum transverse aortic diameter will be assessed regularly for 5 years by a combination of computed tomography and duplex sonography. RESULTS: Four patients have thus far been enrolled, randomized, and treated per protocol. We anticipate the conclusion of the treatment phase within the next 24 months with ongoing long-term follow-up. CONCLUSIONS: ARREST will be pivotal in assessing the safety of MSC infusion and provide preliminary data on the ability of MSCs to favorably modulate the pathogenic AAA host immune response. The data gleaned from this phase I trial will provide the groundwork for a larger, phase III RCT which may provide the first pharmaceutical intervention for AAA.
RCT Entities:
BACKGROUND:Abdominal aortic aneurysms (AAAs) are a major source of morbidity and mortality despite continuing advances in surgical technique and care. Although the inciting factors for AAA development continue to be elusive, accumulating evidence suggests a significant periaortic inflammatory response leading to degradation and dilation of the aortic wall. Previous human trials have demonstrated safety and efficacy of mesenchymal stem cells (MSCs) in the treatment of inflammation-related pathologies such as rheumatoid arthritis, graft versus host disease, and transplant rejection. Therefore, herein, we describe the Aortic Aneurysm Repression with Mesenchymal Stem Cells (ARREST) trial, a phase I investigation into the safety of MSC infusion for patients with small AAA and the cells' effects on modulation of AAA-related inflammation. METHODS: ARREST is a phase I, single-center, double-blind, randomized controlled trial (RCT) investigating infusion both dilute and concentrated MSCs compared to placebo in 36 small AAA (35-45 mm) patients. Subjects will be followed by study personnel for 12 months to ascertain incidence of adverse events, immune cell phenotype expression, peripheral cytokine profile, and periaortic inflammation. Maximum transverse aortic diameter will be assessed regularly for 5 years by a combination of computed tomography and duplex sonography. RESULTS: Four patients have thus far been enrolled, randomized, and treated per protocol. We anticipate the conclusion of the treatment phase within the next 24 months with ongoing long-term follow-up. CONCLUSIONS: ARREST will be pivotal in assessing the safety of MSC infusion and provide preliminary data on the ability of MSCs to favorably modulate the pathogenic AAA host immune response. The data gleaned from this phase I trial will provide the groundwork for a larger, phase III RCT which may provide the first pharmaceutical intervention for AAA.
Authors: S Keisin Wang; Linden A Green; Ashley R Gutwein; Natalie A Drucker; Raghu L Motaganahalli; Alok K Gupta; Andres Fajardo; Michael P Murphy Journal: Surgery Date: 2018-04-30 Impact factor: 3.982
Authors: Ke Li; Deborah Vela; Elton Migliati; Maria da Graca Cabreira; Xiaohong Wang; L Maximilian Buja; Emerson C Perin Journal: Cell Transplant Date: 2021 Jan-Dec Impact factor: 4.064
Authors: David Ben-Israel; Brooke L Belanger; Amin Adibi; Muneer Eesa; Alim P Mitha; Eldon Spackman Journal: PLoS One Date: 2021-08-09 Impact factor: 3.240