Mesenchymal Stem Cells Transplantation for Ischemic-type Biliary Lesions

Umbilical Cord Mesenchymal Stem Cells Transplantation for Treatment of Patients With Ischemic-type Biliary Lesions After Liver Transplantation

Ischemic-type biliary lesions (ITBLs) are a major cause of graft loss and mortality after orthotopic liver transplantation (OLT). For now, there are still lacking effective treatment for ITBLs. The purpose of this study is to confirm whether human umbilical cord mesenchymal stem cells are effective in the treatment,or prevention of Ischemic-type Biliary Lesions after liver transplantation.

Study Overview

• Status: Unknown
• Conditions: Ischemic-type Biliary Lesions
• Intervention / Treatment: Drug: huc-MSCs; Drug: Placebo

Detailed Description

Advances in organ preservation techniques, immunosuppressive regimens, and surgical techniques have resulted in reduced rates of infection, acute rejection and vascular complications after orthotopic liver transplantation (OLT). However, ischemic-type biliary lesions (ITBLs) are still one of the most serious complications after OLT, with a usual reported incidence of 5-15%, and an incidence of up to 26% in some studies. 46% patients with ITBLs require re-transplantation after 2 years of OLT.

Mesenchymal stem cells (MSCs),a kind of pluripotent stem cells,can differentiate into vascular endothelial cells, which participate in angiogenesis in ischemic tissue. MSCs can also stimulate the proliferation and migration of mature endothelial cells via paracrine.Furthermore, MSCs secret a variety of cytokines and growth factors, such as vascular endothelial growth factor, human basic fibroblast growth factor, hepatocyte growth factor, interleukin-1 and interleukin-8, etc., which also induce angiogenesis.

Participants in the study will be randomly assigned to one of two treatment arms:

• Arm A: Participants will receive 6 months of standard regular treatment for ITBLs plus huc-MSCs treatment.
• Arm B: Participants will receive 6 months of standard regular treatment for ITBLs plus placebo.

huc-MSCs will be prepared according to standard procedures and is collected in plastic bags containing anti coagulant. MSCs are given via i.v. After huc-MSCs transfusion, patients are followed up once per week(in the first months,<1M),once per 2 week(1-3M)and once per month(3-6M), and the evaluation of liver function and biliary blood supply was performed.

• Study Type: Interventional
• Enrollment (Anticipated): 66
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • Third Affiliated Hospital, Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• benign end-stage liver disease patients with liver transplantation.
• ages of 18 and 60 years.
• first liver transplant.
• gamma-glutamyltransferase > 300 U/L for 2 weeks, and there was no or low enhancement of the wall of the hilar bile duct in arterial phase via contrast-enhanced ultrasonography.
• Written informed consent.

Exclusion Criteria:

• second or combined organ transplant recipient.
• vital organs failure (Cardiac, Renal or Respiratory, et al).
• clinically active bacterial, fungal, viral or parasitic infection.
• other candidates who are judged to be not applicable to this study by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Conventional treatment, huc-MSCs; Received conventional treatment and huc-MSCs once per week for the first month and once per month for 6 months(9 times in total), at a dose of 1×106 huc-MSCs/kg body weight.	Drug: huc-MSCs; Received conventional treatment and huc-MSCs once per week for the first month and once per month for 6 months(9 times in total), at a dose of 1×106 huc-MSCs/kg body weight.; Other Names: Umbilical Cord-Derived Mesenchymal Stem Cells
PLACEBO_COMPARATOR: Conventional plus placebo; Received conventional treatment and 50 ml saline once per week for the first month and once per month for 6 months(9 times in total).	Drug: Placebo; Received conventional treatment and 50 ml saline solution once per week for the first month and once per month for 6 months(9 times in total).; Other Names: saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of ITBLs	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in biliary enzymology		18 months
Biliary blood supply	Biliary blood supply indicated by contrast-enhanced ultrasound.	18 months

Other Outcome Measures

Outcome Measure	Time Frame
life quality	18 months

Collaborators and Investigators

• Sponsor: Yang Yang

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (ANTICIPATED): June 1, 2017
• Study Completion (ANTICIPATED): June 1, 2018

Study Registration Dates

• First Submitted: August 21, 2014
• First Submitted That Met QC Criteria: August 21, 2014
• First Posted (ESTIMATE): August 22, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): August 22, 2014
• Last Update Submitted That Met QC Criteria: August 21, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Liver transplantation; mesenchymal stem cells; Biliary complication
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: 2014006