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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by Chinese Academy of Medical Sciences.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Peking Union Medical College Hospital
Information provided by (Responsible Party):
Robert Chunhua Zhao, MD, PhD, Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01440309
First received: September 20, 2011
Last updated: August 1, 2012
Last verified: September 2011
  Purpose

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).


Condition Intervention Phase
Primary Biliary Cirrhosis
Biological: Biological: mesenchymal stem cell
Drug: ursodeoxycholic acid
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial, Randomized, Controlled, to Evaluate the Efficacy and Safety of Therapy With Allogenic Mesenchymal Stem Cells From Bone Marrow for Patients With Refractory Primary Biliary Cirrhosis

Resource links provided by NLM:


Further study details as provided by Chinese Academy of Medical Sciences:

Primary Outcome Measures:
  • serum level of alkaline phosphatase [ Time Frame: 24 months after MSCs administration ] [ Designated as safety issue: Yes ]
    Serum level of alkaline phosphatase will be measured at entry, 1 months,3 months, 6 months and 24 months after therapy


Secondary Outcome Measures:
  • histological changes in liver biopsies [ Time Frame: 6 months after therapy ] [ Designated as safety issue: No ]
    Liver biopsy of each patient will be taken before entry into therapeutic trials and at 6 months after therapy.

  • Serum levels of TNF-alpha [ Time Frame: 6 months after therapy ] [ Designated as safety issue: No ]
    serum levels of TNF-alpha will be assessed before entry into therapeutic trials and at 6 months after therapy

  • changes in fatigue [ Time Frame: 6 months after theraphy ] [ Designated as safety issue: No ]
    changes in fatigue will be evaluated before test (baseline), 1 month,3 months and 6 months after theraphy by PBC-40 score.

  • The occurrence of cirrhosis and its complications [ Time Frame: 24 months after therapy ] [ Designated as safety issue: No ]
  • Serum levels of Interleukin [ Time Frame: 6 months after therapy ] [ Designated as safety issue: No ]
    serum levels of Interleukin will be assessed before entry into therapeutic trials and at 6 months after therapy

  • changes in pruritus severity [ Time Frame: 6 months after therapy ] [ Designated as safety issue: No ]
    changes in pruritus severity will be evaluated before test (baseline), 1 month,3 months and 6 months after theraphy by VAS score.


Estimated Enrollment: 20
Study Start Date: November 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: allogenic mesenchymal stem cells (MSCs)
Patients who have primary biliary cirrhosis.
Biological: Biological: mesenchymal stem cell
Mesenchymal stem cells,5-50 million/kg, Intravenous infusion, One dosage,whether to give another dosage depending on patients' condition
Other Name: regenerative medicine:MSCs
Active Comparator: ursodeoxycholic acid (UDCA)
Patients who have primary biliary cirrhosis.
Drug: ursodeoxycholic acid
13-15 mg/kg/day, to the end of the study
Other Name: UDCA

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01440309

Contacts
Contact: Fengchun Zhang, MD 0086-10-65296891 zhangfccra@yahoo.com.cn
Contact: Yunjiao Yang, MD 0086-10-65295047 yangyunjiao81@163.com

Locations
China
Peking Union Medical College Hospital Recruiting
Beijing, China
Contact: Fengchun Zhang, MD       zhangfccra@yahoo.com.cn   
Sponsors and Collaborators
Robert Chunhua Zhao, MD, PhD
Peking Union Medical College Hospital
Investigators
Principal Investigator: Fengchun Zhang, MD Peking Union Medical College Hospital
Principal Investigator: Robert Chunhua Zhao, MD,PhD Chinese Academy of Medical Sciences
  More Information

Publications:

Responsible Party: Robert Chunhua Zhao, MD, PhD, MD, PhD,Professor of medicine, Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier: NCT01440309     History of Changes
Other Study ID Numbers: 2008BAI59B03/2011AA020119
Study First Received: September 20, 2011
Last Updated: August 1, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Chinese Academy of Medical Sciences:
biliary cirrhosis

Additional relevant MeSH terms:
Liver Cirrhosis, Biliary
Liver Cirrhosis
Fibrosis
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases
Pathologic Processes
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014