Mesenchymal Stem Cell in Patients With Acute Severe Respiratory Failure

Respiratory Distress Syndrome, Adult Clinical Trial

— STELLAR  

Official title:

A Pilot Study for the Efficacy and Safety of Mesenchymal Stem Cell in Acute Severe Respiratory Failure.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02112500
• Other study ID #: STELLAR-Pilot
• Status: Recruiting
• Phase: Phase 2
• First received: March 30, 2014
• Last updated: January 8, 2016
• Start date: February 2014
• Est. completion date: December 2016

Study information

• Verified date: January 2016
• Source: Asan Medical Center
• Contact: Sang Bum Hong, MD
• Phone: +82-10-6824-9767
• Email: hongsangbum[@]gmail.com
• Is FDA regulated: No
• Health authority: Korea: Institutional Review BoardKorea: Ministry of Food and Drug Safety
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lung Injury
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Respiratory Insufficiency

Intervention

Biological:
• Mesenchymal Stem Cell
Mesenchymal stem cells will be intravenously infused. Mesenchymal stem cells will be cultured and extracted from the bone marrow of the patients.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (11)

Calfee CS, Matthay MA. Nonventilatory treatments for acute lung injury and ARDS. Chest. 2007 Mar;131(3):913-20. Review. — View Citation

D'Agostino B, Sullo N, Siniscalco D, De Angelis A, Rossi F. Mesenchymal stem cell therapy for the treatment of chronic obstructive pulmonary disease. Expert Opin Biol Ther. 2010 May;10(5):681-7. doi: 10.1517/14712591003610614. Review. — View Citation

Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 2007 Aug 1;179(3):1855-63. — View 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. — View Citation

Lee JW, Gupta N, Serikov V, Matthay MA. Potential application of mesenchymal stem cells in acute lung injury. Expert Opin Biol Ther. 2009 Oct;9(10):1259-70. doi: 10.1517/14712590903213651. Review. — View 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. — View 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. Epub 2007 Jun 14. — View Citation

Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, Brigham KL. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005 Aug;33(2):145-52. Epub 2005 May 12. — View Citation

Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med. 2005 Oct 20;353(16):1685-93. — View Citation

Stagg J. Immune regulation by mesenchymal stem cells: two sides to the coin. Tissue Antigens. 2007 Jan;69(1):1-9. Review. — View Citation

Zhen G, Liu H, Gu N, Zhang H, Xu Y, Zhang Z. Mesenchymal stem cells transplantation protects against rat pulmonary emphysema. Front Biosci. 2008 May 1;13:3415-22. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oxygen index at 3 days after mesenchymal stem cell infusion	Oxygen index at 3 days after mesenchymal stem cell infusion. Oxygen index is calculated as follows; ((FiO2) x (Mean airway pressure)) / (PaO2)	3 days after mesenchymal stem cell infusion	No
Secondary	Lung mechanics	Lung mechanics includes arterial oxygen saturation, tidal volume, minute ventilation, and ratio of PaO2/FiO2.	at 3, 14, and 28 days after mesenchymal stem cell infusion	No
Secondary	Hemodynamic parameters	Systolic, diastolic, and mean arterial blood pressure Amount of required vasopressor Heart rate	at 3, 14, and 28 days after mesenchymal stem cell infusion	No
Secondary	Mortality	Death from any cause at 14 and 28 days after mesenchymal stem cell infusion	at 14 and 28 days after mesenchymal stem cell infusion	No
Secondary	Plasma cytokines	Interleukin (IL)-1, IL-6, IL-8, and IL-10	at 3, 14, and 28 days after mesenchymal stem cell infusion	No
Secondary	Markers for inflammation and infection	Lactate, DIC score, SOFA score, C-reactive protein, and procalcitonin	at 3, 14, and 28 days after mesenchymal stem cell infusion	No
Secondary	Ventilator weaning parameters	Failure of ventilator weaning, weaning time, ventilation time	at 3, 14, and 28 days after mesenchymal stem cell infusion	No
Secondary	ICU and hospital stay	Total duration of ICU stay and hospital stay	at 28 days after mesenchymal stem cell infusion	No