Efficacy and Safety Study of Allogenic Mesenchymal Stem Cells for Patients With Refractory Primary Biliary Cirrhosis

NCT01440309 | Unknown Phase 1 DMC

• 1 other identifier: 2008BAI59B03/2011AA020119
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Primary Biliary Cirrhosis

Keywords

biliary cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• histological changes in liver biopsies

  6 months after therapy

• Serum levels of TNF-alpha

  6 months after therapy

• changes in fatigue

  6 months after theraphy

• The occurrence of cirrhosis and its complications

  24 months after therapy

• Serum levels of Interleukin

  6 months after therapy

Study Arms (2)

allogenic mesenchymal stem cells (MSCs)

EXPERIMENTAL

Patients who have primary biliary cirrhosis.

Biological: Biological: mesenchymal stem cell

ursodeoxycholic acid (UDCA)

ACTIVE COMPARATOR

Patients who have primary biliary cirrhosis.

Drug: ursodeoxycholic acid

Interventions

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

Also known as: regenerative medicine:MSCs

allogenic mesenchymal stem cells (MSCs)

ursodeoxycholic acid DRUG

13-15 mg/kg/day, to the end of the study

Also known as: UDCA

ursodeoxycholic acid (UDCA)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• There must be at least two of the following: a concentration in serum of AMAs at titres of 1:40 or higher; an unexplained rise in the amount of alkaline phosphatase of at least 1•5 times the upper limit of normal for more than 24 weeks; and compatible liver histological findings, specifically non-suppurative cholangitis and interlobular bile duct injury.
• Incomplete response to UDCA at 13-15 mg/kg/day, Criteria for the group of complete responders is including: concentrations of alkaline phosphatase less than three times the upper limit of normal, aspartate aminotransferase less than twice the upper limit of normal, and bilirubin less than 17 μmol/L;and normalisation of abnormal concentrations of bilirubin, albumin, or both.
• Liver pathological staging in 2 or3, Histological staging is based on Ludwig's and Scheuer's classifications

You may not qualify if:

• Patients are receiving any other investigational agents within 4 weeks of study entry
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined as invasive fungal infection and progressive CMV viremia), symptomatic congestive heart failure (NYH class III and IV), unstable angina pectoris, or cardiac arrhythmia
• In pregnancy or lactation
• Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
• HCVpositive ，HBSAg positive or with other liver diseases
• Combined with other autoimmune disease
• Expected survival time is less than one year
• Decompensation of liver function（Child B or C）
• Have a history of allergy or Allergic constitution

Sponsors & Collaborators

• Robert Chunhua Zhao, MD, PhD: lead
• Peking Union Medical College Hospital: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, China

RECRUITING

Related Publications (10)

• 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.

  PMID: 21235326 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.

  PMID: 21078360 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.

  PMID: 18832657 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.

  PMID: 18673001 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.

  PMID: 15257043 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.

  PMID: 19788697 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.

  PMID: 17999594 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.

  PMID: 16008514 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.

  PMID: 15345288 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.

  PMID: 15186722 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Fengchun Zhang, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

• Robert Chunhua Zhao, MD,PhD

  Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fengchun Zhang, MD

CONTACT

0086-10-65296891; zhangfccra@yahoo.com.cn

Yunjiao Yang, MD

CONTACT

0086-10-65295047; yangyunjiao81@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: UNKNOWN
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD，Professor of medicine

Study Record Dates

• First Submitted: September 20, 2011
• First Posted: September 26, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: December 1, 2013
• Last Updated: August 3, 2012

Record last verified: 2011-09

Locations

CN (1)