ABMSC Infusion Through Hepatic Artery in Portal Hypertension Surgery for the Treatment of Liver Cirrhosis

March 21, 2012 updated by: Qiqiang Zeng, Wenzhou Medical University

Autologous Bone Marrow Stem Cells Infusion Through Hepatic Artery in Open Abdominal Portal Hypertension Surgery for the Treatment of Liver Cirrhosis: a Prospective, Non-randomized, Controlled Study

In recent years, the safety and efficacy of autologous bone marrow stem cells infusion (ABMSCi) therapy were confirmed. The investigators attempted to infuse autologous bone marrow stem cells (ABMSC) through inserting a catheter into right gastric artery as far as proper hepatic artery after finishing open abdominal portal hypertension surgery. The present study was designed to treat bleeding from esophageal varices and hypersplenism and hopefully to improve the liver function as well.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

  1. ABMSC mobilization and harvest

    • For harvesting more ABMSC, ABMSC mobilization was induced by rhG-CSF (Gran○R), administered subcutaneously at a dose of 300μg daily for three consecutive days before open abdominal portal hypertension surgery.
    • Bone marrow (160-200ml) of the patients was harvested from both posterior superior iliac according to standard procedures under local anaesthesia and was collected in a plastic bag containing heparin.

  2. Open abdominal portal hypertension surgery

    - Immediately after the harvest of ABMSC, the modified Sugiura procedure was performed for the patients who were assigned to the study group. The same surgical procedure was also performed for the control group (without harvest of ABMSC and ABMSC infusion).

  3. ABMSC separation and infusion

    • While performing the portal hypertension surgery, ABMSC was separated and purified in a class 10,000 clean laboratory. After fat and bony particles were removed by filtration, collected cells were moved to a cell-processing device. We used the reagent kit ([Patent Number] ZL 2006 1 0106875.5; [Number of Criteria Applicable] YZB/NING YIN 0008-2008; [Researcher and Developer] Wealthlin Science & Technology Inc., Canada; [Producer] Ningxia Zhonglianda Biotech Co., Ltd.). The reagents adopt the method of negative cells collection. Take the cells which intended to remove as target cells, and carry out the removal step-by-step. On the basis of this method, red blood cells, blood platelets, blood plasma will be completely removed with part of white cells and lymphocytes being remarkably removed as well while all the stem cells / progenitor cells are being well retained.
    • The nucleated cell (white blood cell) count of final ABMSC was measured by an automated complete blood count instrument and flow cytometry analysis. The number of mononuclear cells was counted manually under a microscope by Wright-Giemsa stain method. CD34 positive cells were determined by flow cytometry analysis.
    • The time of ABMSC separation and purification was 2.5-3 hours which had to be completed before the conclusion of portal hypertension surgery (3-3.5 hours). ABMSC was added to 10 ml saline and well mixed by shaking the vial gently. Before incision closure, the right gastric artery or right gastroepiploic artery was selected and a catheter was inserted. The catheter was pushed to reach the proper hepatic artery. The diameter of the catheter is 1.4mm, it is thin enough to easily been inserted to right gastric artery or right gastroepiploic artery (central venous catheterization, REF product NO.ES-04218, Arrow International, Inc.). The mixture of saline and AMBC was infused into hepatic artery at uniform speed for about two minutes. The catheter was removed after the ABMSCi. The puncture point of the right gastric artery was repaired using blood vessel suture or transfixed.
  4. Statistical analysis - Categorical data are presented as absolute values and percentages, whereas continuous data are summarized as mean and Standard Deviation. Statistical analysis was performed using t-test for paired or unpaired samples. Time courses of measurements of liver function parameters were analyzed by repeated-measures ANOVA. The analyses were performed using the SPSS 15.0 statistical package (SPSS Inc., Chicago, IL, USA). All statistical analyses were based on two-tailed hypothesis tests with a significance level of p< 0.05.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Zhejiang
      • Wenzhou, Zhejiang, China, 325000
        • Recruiting
        • The First Affiliated Hospital of Wenzhou Medical College
        • Contact:
        • Principal Investigator:
          • qiqiang zeng, MD
        • Principal Investigator:
          • yi liao, MD
        • Principal Investigator:
          • minghua zheng, MD
        • Principal Investigator:
          • bing liang, MD
        • Principal Investigator:
          • qigang xu, MD
        • Principal Investigator:
          • yi wang, MD
        • Principal Investigator:
          • zhengping yu, MD
        • Principal Investigator:
          • hongqi shi, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Advanced liver cirrhosis after hepatitis B resulted in bleeding from esophageal varices and hypersplenism, and needed open abdominal portal hypertension surgery;
  2. Endoscopy evidence of showing severe gastric and esophageal varices;
  3. Severe hypersplenism （white blood cells (WBC) <3×109/L and platelet (PLT) <100×109/L）;
  4. Active bone marrow hyperplasia showed by bone marrow biopsy before surgery;
  5. Age between 18 and 60 years;
  6. Plasma albumin <35g/L, or mild ascites;

Exclusion Criteria:

  1. Enlisted for liver transplantation
  2. Diagnosis of hepatocellular carcinoma or other cancers
  3. Other severe medical disease, and acute infection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ABMSCi plus surgery group
Autologous bone marrow stem cells infusion through hepatic artery in open abdominal portal hypertension surgery
Procedure: Autologous bone marrow stem cells infusion （ABMSCi） plus abdominal portal hypertension surgery
Immediately after the harvest of ABMSC, the modified Sugiura procedure was performed for the patients who were assigned to the study group. The time of ABMSC separation and purification was 2.5-3 hours which had to be completed before the conclusion of portal hypertension surgery (3-3.5 hours). ABMSC was infused into proper hepatic artery through right gastric artery during the portal hypertension surgery
No Intervention: portal hypertension surgery group
only portal hypertension surgery for this group patients
Procedure: open abdominal portal hypertension surgery
the modified Sugiura procedure was performed for the patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Child-pugh score
Time Frame: 1 month after treament
1 month after treament

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of complications
Time Frame: within the first week after treatment
postoperative pyrexia, intraperitoneal hemorrhage, intraperitoneal infection, malignant tumors of liver and other systems
within the first week after treatment
Mortality
Time Frame: 1week, 1 month, 3 month, 6 month, 1 year and 2 year
1week, 1 month, 3 month, 6 month, 1 year and 2 year
blood test (hypersplenism)
Time Frame: whinin 7 days before treatment, 1 week,1,3, 6 and 12 months after treatment
PLT and WBC
whinin 7 days before treatment, 1 week,1,3, 6 and 12 months after treatment
liver volume calculated by CT
Time Frame: whinin 7 days before treatment, 1 month and a year after treatment
estimation of liver volume using CT
whinin 7 days before treatment, 1 month and a year after treatment
Indocyanine green (ICG) retention (clearance)
Time Frame: whinin 7 days before treatment, 1 week,1,3, 6 and 12 months after treatment
whinin 7 days before treatment, 1 week,1,3, 6 and 12 months after treatment
blood biochemistry
Time Frame: whinin 7 days before treatment, 1 week,1,3, 6 and 12 months after treatment
  1. alanine aminotransferase
  2. aspartate aminotransferase
  3. total bilirubin
  4. direct bilirubin
  5. The total bile acid (TBA)
  6. serum cholinesterase (CHE)
  7. albumin
  8. prothrombin time (PT)
  9. international normalized ratio (INR)
whinin 7 days before treatment, 1 week,1,3, 6 and 12 months after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wenzhou Medical University

Investigators

  • Study Chair: qiyu zhang, MD, First Affiliated Hospital of Wenzhou Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Anticipated)

June 1, 2013

Study Completion (Anticipated)

June 1, 2014

Study Registration Dates

First Submitted

March 18, 2012

First Submitted That Met QC Criteria

March 21, 2012

First Posted (Estimate)

March 22, 2012

Study Record Updates

Last Update Posted (Estimate)

March 22, 2012

Last Update Submitted That Met QC Criteria

March 21, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WZMC1-10-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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