title: 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.
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.
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Golpanian
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Darcy L
authors.initials: DL
authors.lastname: DiFede
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Marietsy V
authors.initials: MV
authors.lastname: Pujol
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Maureen H
authors.initials: MH
authors.lastname: Lowery
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.|Division of Endocrinology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Silvina
authors.initials: S
authors.lastname: Levis-Dusseau
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Otolaringology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Goldstein
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.|Division of Nephrology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Ivonne H
authors.initials: IH
authors.lastname: Schulman
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Bangon
authors.initials: B
authors.lastname: Longsomboon
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Aisha
authors.initials: A
authors.lastname: Khan
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.|Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Heldman
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.|Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Pascal J
authors.initials: PJ
authors.lastname: Goldschmidt-Clermont
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.|Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D016330:Frail Elderly; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D007262:Infusions, Intravenous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D011379:Prognosis; D044968:Regenerative Medicine; D012107:Research Design; D015996:Survival Rate; D014184:Transplantation, Homologous
keywords: Gerotarget; aging; allogeneic; frailty; mesenchymal stem cells