Umbilical Cord Derived Mesenchymal Stem Cells Transplantation for Active and Refractory Systemic Lupus Erythematosus
Study Details
Study Description
Brief Summary
This study will explore safety and efficacy of allogeneic umbilical cord (UC) derived mesenchymal stem cells transplantation (MSCT) to treat patients with active and refractory systemic lupus erythematosus (SLE) who have been resistant to multiple standard treatments. The underlying hypothesis is that the active SLE condition is caused by an abnormal immune homeostasis that can be restored by MSCT.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Inclusion Criteria:
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All patients fulfilled the American College of Rheumatology (ACR) criteria of SLE, man or woman aged from 15 to 70 years old, SLEDAI≥8;
-
Lupus nephritis with 24h urine protein≥1g;
-
Refractory disease as determined by failure of the following regimens:
Trial of corticosteroids (oral prednisone more than 20 mg/day); Trial of cyclophosphamide 0.4 ~ 0.6 / m2 every two weeks for six months, or other immunosuppressive drugs, such as mycophenolate mofetil 2 g / day, for three months;
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Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital;
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Willing to use contraception throughout the study and for 12 months following treatment
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: human umbilical cord derived MSC human umbilical cord derived MSC transplantation for SLE |
Biological: human umbilical cord derived MSC transplantation for SLE
Other Names:
|
Outcome Measures
Primary Outcome Measures
- British Isles Lupus Assessment Group score (BILAG) [up to 12 months]
Secondary Outcome Measures
- Lupus serology (Alb, ANA, dsDNA, C3, C4) [pre-MSC transplantation, 1, 3, 6 and 12 months post MSC transplantation]
- Renal function (GFR, Blood Urea Nitrogen, urinalysis) [pre-MSC transplantation, 1, 3, 6 and 12 months post MSC transplantation (for GFR assessed at baseline and 12 months after MSCT)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
All patients fulfilled the American College of Rheumatology (ACR) criteria of SLE, man or woman aged from 15 to 60 years old, SLEDAI≥8;
-
Lupus nephritis with 24h urine protein≥1g;
-
Refractory disease as determined by failure of the following regimens:
Trial of corticosteroids (oral prednisone more than 20 mg/day); Trial of cyclophosphamide 0.4 ~ 0.6 / m2 every two weeks for six months, or other immunosuppressive drugs, such as mycophenolate mofetil 2 g / day, for three months;
-
Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital;
-
Willing to use contraception throughout the study and for 12 months following treatment
Exclusion Criteria:
-
Abnormal liver function (ALT higher than 3 times the normal value);
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End-stage renal failure;
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Severe heart and pulmonary failure, or other important organs damage;
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Uncontrolled infections
-
Pregnant or breast feeding women, male or female who intended to recent pregnancy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Affiliated Drum Tower Hospital of Nanjing University Medical School | Nanjing | Jiangsu | China | 210008 |
Sponsors and Collaborators
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Investigators
- Principal Investigator: Lingyun Sun, MD, PhD, the Affiliated Drum Tower Hospital of Nanjing University Medical School
Study Documents (Full-Text)
None provided.More Information
Publications
- Che N, Li X, Zhou S, Liu R, Shi D, Lu L, Sun L. Umbilical cord mesenchymal stem cells suppress B-cell proliferation and differentiation. Cell Immunol. 2012;274(1-2):46-53. doi: 10.1016/j.cellimm.2012.02.004. Epub 2012 Feb 23.
- Liang J, Gu F, Wang H, Hua B, Hou Y, Shi S, Lu L, Sun L. Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE. Nat Rev Rheumatol. 2010 Aug;6(8):486-9. doi: 10.1038/nrrheum.2010.80. Epub 2010 Jun 1.
- Liang J, Zhang H, Hua B, Wang H, Lu L, Shi S, Hou Y, Zeng X, Gilkeson GS, Sun L. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis. 2010 Aug;69(8):1423-9. doi: 10.1136/ard.2009.123463. Erratum in: Ann Rheum Dis. 2011 Jan;70(1):237.
- Shi D, Wang D, Li X, Zhang H, Che N, Lu Z, Sun L. Allogeneic transplantation of umbilical cord-derived mesenchymal stem cells for diffuse alveolar hemorrhage in systemic lupus erythematosus. Clin Rheumatol. 2012 May;31(5):841-6. doi: 10.1007/s10067-012-1943-2.
- Sun L, Akiyama K, Zhang H, Yamaza T, Hou Y, Zhao S, Xu T, Le A, Shi S. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells. 2009 Jun;27(6):1421-32. doi: 10.1002/stem.68.
- Sun L, Wang D, Liang J, Zhang H, Feng X, Wang H, Hua B, Liu B, Ye S, Hu X, Xu W, Zeng X, Hou Y, Gilkeson GS, Silver RM, Lu L, Shi S. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum. 2010 Aug;62(8):2467-75. doi: 10.1002/art.27548.
- Wang D, Akiyama K, Zhang H, Yamaza T, Li X, Feng X, Wang H, Hua B, Liu B, Xu H, Chen W, Shi S, Sun L. Double allogenic mesenchymal stem cells transplantations could not enhance therapeutic effect compared with single transplantation in systemic lupus erythematosus. Clin Dev Immunol. 2012;2012:273291. doi: 10.1155/2012/273291. Epub 2012 Jul 9.
- Zhang H, Zeng X, Sun L. Allogenic bone-marrow-derived mesenchymal stem cells transplantation as a novel therapy for systemic lupus erythematosus. Expert Opin Biol Ther. 2010 May;10(5):701-9. doi: 10.1517/14712591003769816. Review.
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