Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome

Kathleen D Liu¹, Jennifer G Wilson², Hanjing Zhuo³, Lizette Caballero⁴, Melanie L McMillan⁴, Xiaohui Fang³, Katherine Cosgrove⁵, Carolyn S Calfee⁶, Jae-Woo Lee⁷, Kirsten N Kangelaris⁸, Jeffrey E Gotts⁶, Angela J Rogers⁹, Joseph E Levitt⁹, Jeanine P Wiener-Kronish¹⁰, Kevin L Delucchi¹¹, Andrew D Leavitt¹², David H McKenna¹³, B Taylor Thompson⁵, Michael A Matthay¹⁴

Affiliations

¹ Departments of Nephrology and Anesthesia, University of California, San Francisco, CA, USA.
² Departments of Emergency Medicine and Critical Care Medicine, University of California, San Francisco, CA, USA.
³ Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
⁴ Clinical Laboratories, Bone Marrow Center, University of California, San Francisco, CA, USA.
⁵ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
⁷ Department of Anesthesia, University of California, San Francisco, CA, USA.
⁸ Division of Hospital Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
⁹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
¹⁰ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard University, Cambridge, MA, USA.
¹¹ Department of Psychiatry, University of California, San Francisco, CA, USA.
¹² Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
¹³ Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
¹⁴ Departments of Medicine and Anesthesia and the Cardiovascular Research Institute, University of California, San Francisco, CA, USA.

PMID: 25593740
PMCID: PMC4273700
DOI: 10.1186/s13613-014-0022-z

Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome

Kathleen D Liu et al. Ann Intensive Care. 2014.

. 2014 Jul 3:4:22.

doi: 10.1186/s13613-014-0022-z. eCollection 2014.

Authors

Affiliations

¹ Departments of Nephrology and Anesthesia, University of California, San Francisco, CA, USA.
² Departments of Emergency Medicine and Critical Care Medicine, University of California, San Francisco, CA, USA.
³ Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
⁴ Clinical Laboratories, Bone Marrow Center, University of California, San Francisco, CA, USA.
⁵ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
⁷ Department of Anesthesia, University of California, San Francisco, CA, USA.
⁸ Division of Hospital Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
⁹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
¹⁰ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard University, Cambridge, MA, USA.
¹¹ Department of Psychiatry, University of California, San Francisco, CA, USA.
¹² Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
¹³ Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
¹⁴ Departments of Medicine and Anesthesia and the Cardiovascular Research Institute, University of California, San Francisco, CA, USA.

PMID: 25593740
PMCID: PMC4273700
DOI: 10.1186/s13613-014-0022-z

Abstract

Background: Despite advances in supportive care, moderate-severe acute respiratory distress syndrome (ARDS) is associated with high mortality rates, and novel therapies to treat this condition are needed. Compelling pre-clinical data from mouse, rat, sheep and ex vivo perfused human lung models support the use of human mesenchymal stem (stromal) cells (MSCs) as a novel intravenous therapy for the early treatment of ARDS.

Methods: This article describes the study design and challenges encountered during the implementation and phase 1 component of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of bone marrow-derived human MSCs for moderate-severe ARDS. A trial enrolling 69 subjects is planned (9 subjects in phase 1, 60 subjects in phase 2 treated with MSCs or placebo in a 2:1 ratio).

Results: This report describes study design features that are unique to a phase 1 trial in critically ill subjects and the specific challenges of implementation of a cell-based therapy trial in the ICU.

Conclusions: Experience gained during the design and implementation of the START study will be useful to investigators planning future phase 1 clinical trials based in the ICU, as well as trials of cell-based therapy for other acute illnesses.

Clinical trials registration: NCT01775774 and NCT02097641.

Keywords: Acute lung injury; Clinical trial; Mesenchymal stem/stromal cell; Pulmonary edema.

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Figures

**Figure 1**
**Flow diagram for the phase 1 component of the START trial.** Abbreviations are as follows: acute respiratory distress syndrome, ARDS; adverse event, AE; bone marrow transplantation, BMT; Data Safety Monitoring Board, DSMB; positive end-expiratory pressure, PEEP.

See this image and copyright information in PMC

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Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome

Affiliations

Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome

Authors

Affiliations

Abstract

Figures

References

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical