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Autologous Bone Marrow Stem Cells Infusion for the Treatment of Liver Diseases.

Phase 2
Conditions
Liver Diseases
Interventions
Procedure: Autologous bone marrow stem cells infusion
Drug: drugs such as Ursodeoxycholic Acid tablets
Registration Number
NCT02943707
Lead Sponsor
Wenzhou Medical University
Brief Summary

This study evaluates the effect of autologous bone marrow stem cells infusion (ABMSCi) therapy for liver diseases.Treatment group will receive ABMSCi and drugs therapy ,while control group will only receive drugs therapy.

Detailed Description

1. Autologous bone marrow stem cells (ABMSC) mobilization and harvest For harvesting more ABMSC, ABMSC mobilization is induced by recombinant human granulocyte colony stimulating factor (rhGCSF,Gran○R), administered subcutaneously at a dose of 300μg daily for three consecutive days before bone marrow puncture.

Bone marrow (160-200ml) of the patients is harvested from both posterior superior iliacs according to standard procedures under local anaesthesia and is collected in a plastic bag containing heparin.

2. Both treatment group and control group receive drugs therapy.

3. ABMSC separation and infusion ABMSC is separated and purified in a class 10,000 clean laboratory. After fat and bony particles are removed by filtration, collected cells are moved to a cell-processing device. 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 is measured by an automated complete blood count instrument and flow cytometry analysis. The number of mononuclear cells is counted manually under a microscope by Wright-Giemsa stain method. Cell differentiation factor 34(CD34) positive cells were determined by flow cytometry analysis.

The time of ABMSC separation and purification is 2.5-3 hours. ABMSC is added to 10 ml saline and well mixed by shaking the vial gently. The catheter is 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 . The mixture of saline and ABMSC is infused into proper hepatic artery at uniform speed for about two minutes. The catheter is removed after the ABMSCi.

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 analysis is performed using the Statistic Package for Social Science (SPSS). All statistical analysis is based on two-tailed hypothesis tests with a significance level of p\< 0.05.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
40
Inclusion Criteria
  1. Definite liver diseases (such as viral hepatitis, autoimmune liver diseases, fatty liver diseases, ect);
  2. Active bone marrow hyperplasia showed by bone marrow biopsy before ABMSCi;
  3. Age between 18 and 60 years;
  4. Abnormal liver function.
Exclusion Criteria
  1. Enlisted for liver transplantation
  2. Diagnosis of hepatocellular carcinoma or other cancers
  3. Other severe medical disease, and acute infection
  4. pregnant or nursing females,co-infections with HIV ,serious bacterial infection
  5. other vital organ or system dysfunction
  6. with severe complications of liver cirrhosis
  7. hematological disorder

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
treatment group: ABMSCi & drugsdrugs such as Ursodeoxycholic Acid tabletsABMSCi: Autologous bone marrow stem cells infusion drugs such as Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally
control group: drugsdrugs such as Ursodeoxycholic Acid tabletsdrugs such as Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally
treatment group: ABMSCi & drugsAutologous bone marrow stem cells infusionABMSCi: Autologous bone marrow stem cells infusion drugs such as Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally
Primary Outcome Measures
NameTimeMethod
Change from baseline alanine aminotransferase at 6 monthsbaseline and 6 months after treatment

alanine aminotransferase (ALT)

Change from baseline total bilirubin at 6 monthsbaseline and 6 months after treatment

total bilirubin (TBil)

Change from baseline direct bilirubin at 6 monthsbaseline and 6 months after treatment

direct bilirubin (DBil)

Change from baseline total bile acid at 6 monthsbaseline and 6 months after treatment

total bile acid (TBA)

Change from baseline albumin at 6 monthsbaseline and 6 months after treatment

albumin (ALB)

Change from baseline aspartate aminotransferase at 6 monthsbaseline and 6 months after treatment

aspartate aminotransferase (AST)

Change from baseline prothrombin time at 6 monthsbaseline and 6 months after treatment

prothrombin time (PT),

Change from baseline international normalized ratio at 6 monthsbaseline and 6 months after treatment

international normalized ratio (INR)

Change from baseline white blood cell at 6 monthsbaseline and 6 months after treatment

white blood cell (WBC)

Change from baseline platelet at 6 monthsbaseline and 6 months after treatment

platelet (PLT)

Secondary Outcome Measures
NameTimeMethod
Change from baseline liver density at 6 monthsbaseline and 6 months after treatment

Low density, medium density, high density tested by abdominal B ultrasound/CT/MRI

Change from baseline liver size at 6 monthsbaseline and 6 months after treatment

Enlarged size, normal size, shrunken size tested by abdominal B ultrasound/CT/MRI

Change from baseline spleen thickness at 6 monthsbaseline and 6 months after treatment

tested by abdominal B ultrasound/CT/MRI

Incidence of adverse events that are related to treatmentbaseline and 6 months after treatment

Postoperative pyrexia, infection, liver cirrhosis, ascites, upper gastrointestinal hemorrhage, malignant tumors of liver and other organs

Number of participants that survive without developing disease12 months after treatment
Number of participants that survive with developing disease12 months after treatment
Number of participants that die after treatment12 months after treatment

Trial Locations

Locations (1)

the First Affiliated Hospital of Wenzhou Medical University

🇨🇳

Wenzhou, Zhejiang, China

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