Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty

Samuel Golpanian, Darcy L. DiFede, Marietsy V. Pujol, Maureen H. Lowery, Silvina Levis-Dusseau, Bradley J. Goldstein, Ivonne H. Schulman, Bangon Longsomboon, Ariel Wolf, Aisha Khan, Alan W. Heldman, Pascal J. Goldschmidt-Clermont and Joshua M. Hare _

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Oncotarget. 2016; 7:11899-11912. https://doi.org/10.18632/oncotarget.7727

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Abstract

Samuel Golpanian1,2, Darcy L. DiFede1, Marietsy V. Pujol1, Maureen H. Lowery3, Silvina Levis-Dusseau3,5, Bradley J. Goldstein1,7, Ivonne H. Schulman1,3,6, Bangon Longsomboon1, Ariel Wolf1, Aisha Khan1, Alan W. Heldman1,3,4, Pascal J. Goldschmidt-Clermont3,4 and Joshua M. Hare1,3,4

1 Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA

2 Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA

3 Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA

4 Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL, USA

5 Division of Endocrinology, University of Miami Miller School of Medicine, Miami, FL, USA

6 Division of Nephrology, University of Miami Miller School of Medicine, Miami, FL, USA

7 Department of Otolaringology, University of Miami Miller School of Medicine, Miami, FL, USA

Correspondence to:

Joshua M. Hare, email:

Keywords: aging, frailty, mesenchymal stem cells, allogeneic, Gerotarget

Received: December 20, 2015 Accepted: January 30, 2016 Published: February 25, 2016

Abstract

Frailty is a syndrome associated with reduced physiological reserves that increases an individual’s vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.


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