Clinical Trial: Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST)

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST): An Open Label Dose Escalation Phase 1 Trial Followed by a Randomized, Double-blind,

Brief Summary: Acute Respiratory Distress Syndrome (ARDS) causes the lungs to fail due to the collection of fluid in the lungs (pulmonary oedema). ARDS is common in severely ill patients in Intensive Care Units and is associated with a high mortality and a high morbidity in those who survive. There is a large economic burden with direct healthcare costs, but also indirectly due to the impact on the carer and patient through the patients inability to return to full time employment. There is little evidence for effective drug (pharmacological) treatment for ARDS. There is increasing information that mesenchymal stem cells (MSCs) might be important in treating ARDS. REALIST will investigate if a single infusion of MSCs will help in the treatment of ARDS. The first step will be to first of all determine what dose of MSCs is safe and then divide patients suffering from ARDS into two groups, one of which will get MSCs and the other a harmless dummy (or placebo) infusion, who will then be followed up to determine if lung function improves. If effective this may lead to further research to determine if MSCs are effective in patients with ARDS. This project will also provide new information about mechanisms in the development of ARDS leading, potentially, to other new treatments

Detailed Summary:

The role of MSCs as a novel treatment in ARDS. Mesenchymal Stem Cells (MSCs) are a mononuclear cell population that have the potential to differentiate into multiple lineages, and bone, cartilage and adipocyte cells in particular. Cell-based therapies have been termed the "next pillar of Medicine". MSCs constitute an innovative approach with substantial therapeutic promise for ARDS. MSCs possess several favorable biological characteristics, including convenient isolation, ease of expansion in culture while maintaining genetic stability, minimal immunogenicity and feasibility for allogenic transplantation.

MSCs reduce inflammation and enhance bacterial clearance during rodent and murine bacterial pneumonia, and augment repair of the animal and human lung. Large animal studies have also replicated these beneficial effects. Bone marrow derived (BM) hMSCs decreased acute lung injury (ALI), without producing organ toxicity, in endotoxin injured pigs. Two randomised small phase 1 studies of plastic adherent MSCs in patients with ARDS have taken place. In Japan, investigators used adipose-derived plastic adherent cells in a small cohort (n=12) of patients with ARDS randomized 1:1 to MSCs or placebo: showing that the cells were safe and well-tolerated in this patient group, and were associated with reduced plasma levels of the alveolar epithelial cell injury marker SP-D. In the US Matthay has completed the phase 1 START trial, using a dose escalation study of plastic adherent bone marrow derived MSCs, in patients with moderate to severe ARDS. START showed that marrow derived MSCs at similar doses to those proposed in this study are safe and well-tolerated, (n=9), with a trend to reduced lung injury in the group treated with the highest (10x106cells/kg) compared with the lower doses, 1-5x106cells/kg.

Research hypothesis:<
Sponsor: Belfast Health and Social Care Trust

Current Primary Outcome:

  • Oxygenation index (OI) [ Time Frame: Day 7 ]
    OI is a physiological index of the severity of ARDS and measures both impaired oxygenation and the amount of mechanical ventilation delivered
  • Incidence of Serious Adverse Events (SAEs) [ Time Frame: 28 days ]
    Incidence of SAEs


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Oxygenation index [ Time Frame: Days 4 and 14 ]
  • Sequential Organ Failure Assessment (SOFA) score [ Time Frame: Days 4, 7 and 14 ]
    SOFA score is a measure of organ failure
  • Respiratory compliance (Crs) [ Time Frame: Days 4, 7 and 14 ]
    Crs is a physiological measure of pulmonary function in ARDS
  • Partial pressure of arterial oxygen to the fraction of inspired oxygen ratio (P/F ratio) [ Time Frame: Days 4, 7 and 14 ]
    P/F ratio is a physiological measure of pulmonary function in ARDS


Original Secondary Outcome: Same as current

Information By: Belfast Health and Social Care Trust

Dates:
Date Received: February 1, 2017
Date Started: September 2017
Date Completion: September 2020
Last Updated: February 2, 2017
Last Verified: February 2017