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 Lowery, Silvina Levis, Bradley J Goldstein, Ivonne H Schulman, Bangon Longsomboon, Ariel Wolf, Aisha Khan, Alan W. Heldman, Pascal Goldschmidt-Clermont, Joshua Hare

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)11899-11912
Number of pages14
JournalOncotarget
Volume7
Issue number11
DOIs
StatePublished - Mar 15 2016

Fingerprint

Mesenchymal Stromal Cells
Placebos
Safety
Intravenous Infusions
Cell- and Tissue-Based Therapy
Stem Cells
Clinical Trials
Exercise
Morbidity
Mortality
Therapeutics

Keywords

  • Aging
  • Allogeneic
  • Frailty
  • Gerotarget
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Oncology

Cite this

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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.",
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author = "Samuel Golpanian and DiFede, {Darcy L.} and Pujol, {Marietsy V.} and Maureen Lowery and Silvina Levis and Goldstein, {Bradley J} and Schulman, {Ivonne H} and Bangon Longsomboon and Ariel Wolf and Aisha Khan and Heldman, {Alan W.} and Pascal Goldschmidt-Clermont and Joshua Hare",
year = "2016",
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T1 - Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study

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AU - Golpanian, Samuel

AU - DiFede, Darcy L.

AU - Pujol, Marietsy V.

AU - Lowery, Maureen

AU - Levis, 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

AU - Hare, Joshua

PY - 2016/3/15

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