TY - JOUR
T1 - Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study
T2 - 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
AU - Golpanian, Samuel
AU - DiFede, Darcy L.
AU - Pujol, Marietsy V.
AU - Lowery, Maureen H.
AU - Levis-Dusseau, Silvina
AU - Goldstein, Bradley J.
AU - Schulman, Ivonne H.
AU - Longsomboon, Bangon
AU - Wolf, Ariel
AU - Khan, Aisha
AU - Heldman, Alan W.
AU - Goldschmidt-Clermont, Pascal J.
AU - Hare, Joshua M.
PY - 2016/3/15
Y1 - 2016/3/15
N2 - 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.
AB - 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.
KW - Aging
KW - Allogeneic
KW - Frailty
KW - Gerotarget
KW - Mesenchymal stem cells
UR - http://www.scopus.com/inward/record.url?scp=84962911758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962911758&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.7727
DO - 10.18632/oncotarget.7727
M3 - Article
C2 - 26933813
AN - SCOPUS:84962911758
SN - 1949-2553
VL - 7
SP - 11899
EP - 11912
JO - Oncotarget
JF - Oncotarget
IS - 11
ER -