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| Name | Class |
|---|---|
| Peking Union Medical College Hospital | OTHER |
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The study is designed to evaluate the safety and efficacy of intravenous administration of bone marrow derived mesenchymal stem cells for patients with refractory primary biliary cirrhosis (PBC).
Primary biliary cirrhosis (PBC) is an organ-specific inflammatory disease and characterized by immune mediated destruction of intrahepatic bile ducts, then lead to liver cirrhosis and eventually failure.Currently, ursodeoxycholic acid (UDCA) is the only drug approved by the Food and Drug Administration (FDA). Novel treatment is urgently needed for patients who have an incomplete response to UDCA. Mesenchymal stem cells (MSC) represent a promising tool for cell-based therapies of autoimmune diseases. To explore the therapeutic effect of MSCs for PBC, the investigators plan to conduct an open-label, randomized clinical trial. Patients with PBC will be enrolled and randomly divided into two groups which will receive MSCs and UDCA respectively. The investigators will evaluate the efficacy and safety of MSCs for PBC by comparison of symptom improvement, survival rate and side effects in the two groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| allogenic mesenchymal stem cells (MSCs) | Experimental | Patients who have primary biliary cirrhosis. |
|
| ursodeoxycholic acid (UDCA) | Active Comparator | Patients who have primary biliary cirrhosis. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biological: mesenchymal stem cell | Biological | Mesenchymal stem cells,5-50 million/kg, Intravenous infusion, One dosage,whether to give another dosage depending on patients' condition |
| Measure | Description | Time Frame |
|---|---|---|
| serum level of alkaline phosphatase | Serum level of alkaline phosphatase will be measured at entry, 1 months,3 months, 6 months and 24 months after therapy | 24 months after MSCs administration |
| Measure | Description | Time Frame |
|---|---|---|
| histological changes in liver biopsies | Liver biopsy of each patient will be taken before entry into therapeutic trials and at 6 months after therapy. | 6 months after therapy |
| Serum levels of TNF-alpha |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fengchun Zhang, MD | Contact | 0086-10-65296891 | zhangfccra@yahoo.com.cn | |
| Yunjiao Yang, MD | Contact | 0086-10-65295047 | yangyunjiao81@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Fengchun Zhang, MD | Peking Union Medical College Hospital | Principal Investigator |
| Robert Chunhua Zhao, MD,PhD | Chinese Academy of Medical Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking Union Medical College Hospital | Recruiting | Beijing | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21235326 | Background | Sun Z, Han Q, Zhu Y, Li Z, Chen B, Liao L, Bian C, Li J, Shao C, Zhao RC. NANOG has a role in mesenchymal stem cells' immunomodulatory effect. Stem Cells Dev. 2011 Sep;20(9):1521-8. doi: 10.1089/scd.2010.0366. Epub 2011 Feb 26. | |
| 21078360 | Background | Shi D, Liao L, Zhang B, Liu R, Dou X, Li J, Zhu X, Yu L, Chen D, Zhao RC. Human adipose tissue-derived mesenchymal stem cells facilitate the immunosuppressive effect of cyclosporin A on T lymphocytes through Jagged-1-mediated inhibition of NF-kappaB signaling. Exp Hematol. 2011 Feb;39(2):214-224.e1. doi: 10.1016/j.exphem.2010.10.009. Epub 2010 Nov 13. |
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| ID | Term |
|---|---|
| D008105 | Liver Cirrhosis, Biliary |
| ID | Term |
|---|---|
| D002780 | Cholestasis, Intrahepatic |
| D002779 | Cholestasis |
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
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| ID | Term |
|---|---|
| D014580 | Ursodeoxycholic Acid |
| ID | Term |
|---|---|
| D003840 | Deoxycholic Acid |
| D002793 | Cholic Acids |
| D001647 | Bile Acids and Salts |
| D013256 | Steroids |
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|
| ursodeoxycholic acid | Drug | 13-15 mg/kg/day, to the end of the study |
|
|
serum levels of TNF-alpha will be assessed before entry into therapeutic trials and at 6 months after therapy
| 6 months after therapy |
| changes in fatigue | changes in fatigue will be evaluated before test (baseline), 1 month,3 months and 6 months after theraphy by PBC-40 score. | 6 months after theraphy |
| The occurrence of cirrhosis and its complications | 24 months after therapy |
| Serum levels of Interleukin | serum levels of Interleukin will be assessed before entry into therapeutic trials and at 6 months after therapy | 6 months after therapy |
| changes in pruritus severity | changes in pruritus severity will be evaluated before test (baseline), 1 month,3 months and 6 months after theraphy by VAS score. | 6 months after therapy |
| 18832657 | Background | Zhang B, Liu R, Shi D, Liu X, Chen Y, Dou X, Zhu X, Lu C, Liang W, Liao L, Zenke M, Zhao RC. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Blood. 2009 Jan 1;113(1):46-57. doi: 10.1182/blood-2008-04-154138. Epub 2008 Oct 2. |
| 18673001 | Background | Liao L, Zhao RC. An overview of stem cell-based clinical trials in China. Stem Cells Dev. 2008 Aug;17(4):613-8. doi: 10.1089/scd.2008.0183. |
| 15257043 | Background | Fang B, Shi M, Liao L, Yang S, Liu Y, Zhao RC. Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice. Transplantation. 2004 Jul 15;78(1):83-8. doi: 10.1097/01.tp.0000128326.95294.14. |
| 19788697 | Background | Wang J, Bian C, Liao L, Zhu Y, Li J, Zeng L, Zhao RC. Inhibition of hepatic stellate cells proliferation by mesenchymal stem cells and the possible mechanisms. Hepatol Res. 2009 Dec;39(12):1219-28. doi: 10.1111/j.1872-034X.2009.00564.x. Epub 2009 Sep 25. |
| 17999594 | Background | Chen L, Zhang W, Yue H, Han Q, Chen B, Shi M, Li J, Li B, You S, Shi Y, Zhao RC. Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells. Stem Cells Dev. 2007 Oct;16(5):719-31. doi: 10.1089/scd.2007.0065. |
| 16008514 | Background | Deng W, Han Q, Liao L, You S, Deng H, Zhao RC. Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol. 2005 Jul;24(7):458-63. doi: 10.1089/dna.2005.24.458. |
| 15345288 | Background | Deng W, Han Q, Liao L, Li C, Ge W, Zhao Z, You S, Deng H, Zhao RC. Allogeneic bone marrow-derived flk-1+Sca-1- mesenchymal stem cells leads to stable mixed chimerism and donor-specific tolerance. Exp Hematol. 2004 Sep;32(9):861-7. doi: 10.1016/j.exphem.2004.06.009. |
| 15186722 | Background | Zhang W, Ge W, Li C, You S, Liao L, Han Q, Deng W, Zhao RC. Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev. 2004 Jun;13(3):263-71. doi: 10.1089/154732804323099190. |
| D004066 |
| Digestive System Diseases |
| D008107 | Liver Diseases |
| D008103 | Liver Cirrhosis |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D002757 | Cholanes |