Clinical trial NCT02223897: Mesenchymal Stem Cells Transplantation for Ischemic-type Biliary Lesions
Official title: Umbilical Cord Mesenchymal Stem Cells Transplantation for Treatment of Patients With Ischemic-type Biliary Lesions After Liver Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Ischemic-type Biliary Lesions
Keywords: Liver transplantation
Biliary complication
mesenchymal stem cells
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2014-08-22
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The incidence of ITBLs
timeFrame: 18 months
Secondary outcomes:
measure: Changes in biliary enzymology
timeFrame: 18 months
measure: Biliary blood supply
timeFrame: 18 months
Other outcomes:
measure: life quality
timeFrame: 18 months
Locations:
city: Guangzhou
country: China
facility: Third Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Yang Yang, MD
role: STUDY_CHAIR
References: