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

Oncotarget. 2016 Mar 15;7(11):11899-912. doi: 10.18632/oncotarget.7727.


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.

Keywords: Gerotarget; aging; allogeneic; frailty; mesenchymal stem cells.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Cardiovascular Diseases / immunology
  • Cardiovascular Diseases / prevention & control*
  • Female
  • Follow-Up Studies
  • Frail Elderly
  • Humans
  • Immunity, Innate / immunology*
  • Inflammation / immunology
  • Inflammation / prevention & control*
  • Infusions, Intravenous
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Middle Aged
  • Prognosis
  • Regenerative Medicine
  • Research Design*
  • Survival Rate
  • Transplantation, Homologous