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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by Wenzhou Medical University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Qiqiang Zeng, Wenzhou Medical College
ClinicalTrials.gov Identifier:
NCT01560845
First received: March 18, 2012
Last updated: March 21, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Liver Cirrhosis
Portal Hypertension
Hepatic Decompensation
Surgery
Procedure: Autologous bone marrow stem cells infusion (ABMSCi) plus abdominal portal hypertension surgery
Procedure: open abdominal portal hypertension surgery
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Wenzhou Medical University:

Primary Outcome Measures:
  • Child-pugh score [ Time Frame: 1 month after treament ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of complications [ Time Frame: within the first week after treatment ] [ Designated as safety issue: Yes ]
    postoperative pyrexia, intraperitoneal hemorrhage, intraperitoneal infection, malignant tumors of liver and other systems

  • Mortality [ Time Frame: 1week, 1 month, 3 month, 6 month, 1 year and 2 year ] [ Designated as safety issue: No ]
  • blood test (hypersplenism) [ Time Frame: whinin 7 days before treatment, 1 week,1,3, 6 and 12 months after treatment ] [ Designated as safety issue: No ]
    PLT and WBC

  • liver volume calculated by CT [ Time Frame: whinin 7 days before treatment, 1 month and a year after treatment ] [ Designated as safety issue: No ]
    estimation of liver volume using CT

  • Indocyanine green (ICG) retention (clearance) [ Time Frame: whinin 7 days before treatment, 1 week,1,3, 6 and 12 months after treatment ] [ Designated as safety issue: No ]
  • blood biochemistry [ Time Frame: whinin 7 days before treatment, 1 week,1,3, 6 and 12 months after treatment ] [ Designated as safety issue: No ]
    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)


Estimated Enrollment: 50
Study Start Date: June 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

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

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.
  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: NCT01560845

Contacts
Contact: qiqiang zeng, MD 86-0577-88069307 zengqiqiangwz@163.com

Locations
China, Zhejiang
the First Affiliated Hospital of Wenzhou Medical College Recruiting
Wenzhou, Zhejiang, China, 325000
Contact: qiqiang zeng, MD    86-0577-88069307    zengqiqiangwz@163.com   
Principal Investigator: qiqiang zeng, MD         
Principal Investigator: yi liao, MD         
Principal Investigator: minghua zheng, MD         
Principal Investigator: bing liang, MD         
Principal Investigator: zhiming li, MD         
Principal Investigator: qigang xu, MD         
Principal Investigator: yi wang, MD         
Principal Investigator: zhengping yu, MD         
Principal Investigator: hongqi shi, MD         
Sponsors and Collaborators
Wenzhou Medical University
Investigators
Study Chair: qiyu zhang, MD Wenzhou Medical University
  More Information

Publications:
Responsible Party: Qiqiang Zeng, the secretary-general of stem cell research center of Wenzhou Medical College, Wenzhou Medical College
ClinicalTrials.gov Identifier: NCT01560845     History of Changes
Other Study ID Numbers: WZMC1-10-1
Study First Received: March 18, 2012
Last Updated: March 21, 2012
Health Authority: China: Ethics Committee

Keywords provided by Wenzhou Medical University:
autologous bone marrow stem cells
portal hypertension
surgery
liver cirrhosis

Additional relevant MeSH terms:
Hypertension
Liver Cirrhosis
Hypertension, Portal
Vascular Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on September 30, 2014