Clinical trial NCT02112500: Mesenchymal Stem Cell in Patients With Acute Severe Respiratory Failure
Official title: A Pilot Study for the Efficacy and Safety of Mesenchymal Stem Cell in Acute Severe Respiratory Failure.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Respiratory Distress Syndrome, Adult
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2014-04-14
Enrollment: 10
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Although the advent of advanced medical support for respiratory failure, the mortality rate of acute severe respiratory failure is still high and the life quality is frequently compromised from pulmonary fibrosis.

The investigators hypothesize that the treatment using mesenchymal stem cell can be beneficial in patients with respiratory failure. The present study is a pilot study evaluating the efficacy and safety of mesenchymal stem cell treatment in patients with respiratory failure.

Detailed description: Although the advent of advanced medical support for respiratory failure, the mortality rate of acute severe respiratory failure is still reported to be more than 40%. The respiratory distress syndrome may develop in all ages resulting in progressive pulmonary fibrosis. A number of survivors from respiratory failure suffer from the sequelas of pulmonary fibrosis.

However, the treatments of respiratory failure are limited to the correction of baseline disease, cardiopulmonary support, and conservative management to minimize the lung injury. There has not been any effective and specific treatment for respirator distress nor medicine to reduce mortality.

There have been reports of mesenchymal stem cell experimental animals with chronic obstructive pulmonary disease, interstitial lung disease, and sepsis. In addition, the mesenchymal stem cell treatment showed beneficial effect in bleomycin endotoxin induced lung injury.

Authors hypothesize that the mesenchymal stem cell treatment in patients with respiratory failure will show efficacy. We would conduct the present pilot study to evaluate the efficacy and safety in patients with respiratory failure and intend to suggest an additional alternative treatment option for those without additional treatment option.

Eligibility criteria: Inclusion Criteria:

* Ventilator care from respiratory failure
* Ventilator care for 7 or more days
* at least one of the followings

  1. PaO2/FiO2 = 200 or less when PEEP 5 cmH2O or more.
  2. PaCO2 = 50 mmHg or more when plateau pressure of 30 cmH2O or more.
  3. pH = 7.25 or less when plateau pressure of 30 cmH2O or more.
  4. No other treatment option except for lung transplantation and not candidate for recipient (organ failure, comorbid infection, economy,...)
  5. Ventilatory care with weaning failure 3 times or more
  6. Ventilator care requiring 7 days or more from the first self respiration to weaning of ventilator.

     * PEEP, positive endexpiratory pressure

Exclusion Criteria:

* Severe aplastic anemia
* Malignant hematologic disorder or history of stem cell treatment.
* Currently uncontrolled malignancy or history of solid cancer within 2 years
* HIV Infection
* Expected life \< 3 months from other cause than the respiratory failure
* Pregnancy or breast feeding
* Expected hypersensitivity for study drug

Primary outcomes:
measure: Oxygen index at 3 days after mesenchymal stem cell infusion
timeFrame: 3 days after mesenchymal stem cell infusion
Secondary outcomes:
measure: Lung mechanics
timeFrame: at 3, 14, and 28 days after mesenchymal stem cell infusion
measure: Hemodynamic parameters
timeFrame: at 3, 14, and 28 days after mesenchymal stem cell infusion
measure: Mortality
timeFrame: at 14 and 28 days after mesenchymal stem cell infusion
measure: Plasma cytokines
timeFrame: at 3, 14, and 28 days after mesenchymal stem cell infusion
measure: Markers for inflammation and infection
timeFrame: at 3, 14, and 28 days after mesenchymal stem cell infusion
measure: Ventilator weaning parameters
timeFrame: at 3, 14, and 28 days after mesenchymal stem cell infusion
measure: ICU and hospital stay
timeFrame: at 28 days after mesenchymal stem cell infusion
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Sang Bum Hong, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Lee JW, Fang X, Gupta N, Serikov V, Matthay MA. Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16357-62. doi: 10.1073/pnas.0907996106. Epub 2009 Aug 31.
citation: Ortiz LA, Dutreil M, Fattman C, Pandey AC, Torres G, Go K, Phinney DG. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11002-7. doi: 10.1073/pnas.0704421104. Epub 2007 Jun 14.
citation: Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, Boyd R, Trounson A. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol. 2009 Jul;175(1):303-13. doi: 10.2353/ajpath.2009.080629. Epub 2009 Jun 4.
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