Clinical trial NCT01440309: Efficacy and Safety Study of Allogenic Mesenchymal Stem Cells for Patients With Refractory Primary Biliary Cirrhosis
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Primary Biliary Cirrhosis
Keywords: biliary cirrhosis
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
Collaborators: name: Peking Union Medical College Hospital
First posted: 2011-09-26
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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 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

Primary outcomes:
measure: serum level of alkaline phosphatase
timeFrame: 24 months after MSCs administration
Secondary outcomes:
measure: histological changes in liver biopsies
timeFrame: 6 months after therapy
measure: Serum levels of TNF-alpha
timeFrame: 6 months after therapy
measure: changes in fatigue
timeFrame: 6 months after theraphy
measure: The occurrence of cirrhosis and its complications
timeFrame: 24 months after therapy
measure: Serum levels of Interleukin
timeFrame: 6 months after therapy
measure: changes in pruritus severity
timeFrame: 6 months after therapy
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Peking Union Medical College Hospital
name: Fengchun Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese Academy of Medical Sciences
name: Robert Chunhua Zhao, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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