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

Liver Diseases Clinical Trial

— ABMSCIFTLD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02943707
• Other study ID #: 12330000470005914R
• Status: Recruiting
• Phase: Phase 2
• First received: October 17, 2016
• Last updated: October 21, 2016
• Start date: October 2016
• Est. completion date: October 2020

Study information

• Verified date: October 2016
• Source: Wenzhou Medical University
• Contact: yongping chen
• Phone: 8613505777281
• Email: 13505777281[@]163.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 2020
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Diseases

Intervention

Procedure:
• Autologous bone marrow stem cells infusion
Autologous bone marrow stem cells are infused into proper hepatic artery

Drug:
• drugs such as Ursodeoxycholic Acid tablets
Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally

Locations

Country	Name	City	State
China	the First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Wenzhou Medical University

Country where clinical trial is conducted

China, 

References & Publications (6)

Chen Y, Chen S, Liu LY, Zou ZL, Cai YJ, Wang JG, Chen B, Xu LM, Lin Z, Wang XD, Chen YP. Mesenchymal stem cells ameliorate experimental autoimmune hepatitis by activation of the programmed death 1 pathway. Immunol Lett. 2014 Dec;162(2 Pt B):222-8. doi: 10 — View Citation

Deng Q, Cai T, Zhang S, Hu A, Zhang X, Wang Y, Huang J. Autologous Peripheral Blood Stem Cell Transplantation Improves Portal Hemodynamics in Patients with Hepatitis B Virus-related Decompensated Cirrhosis. Hepat Mon. 2015 Dec 20;15(12):e32498. doi: 10.58 — View Citation

Ma XR, Tang YL, Xuan M, Chang Z, Wang XY, Liang XH. Transplantation of autologous mesenchymal stem cells for end-stage liver cirrhosis: a meta-analysis based on seven controlled trials. Gastroenterol Res Pract. 2015;2015:908275. doi: 10.1155/2015/908275. Epub 2015 Mar 15. Review. — View Citation

Mohamadnejad M, Vosough M, Moossavi S, Nikfam S, Mardpour S, Akhlaghpoor S, Ashrafi M, Azimian V, Jarughi N, Hosseini SE, Moeininia F, Bagheri M, Sharafkhah M, Aghdami N, Malekzadeh R, Baharvand H. Intraportal Infusion of Bone Marrow Mononuclear or CD133+ — View Citation

Peng L, Xie DY, Lin BL, Liu J, Zhu HP, Xie C, Zheng YB, Gao ZL. Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: short-term and long-term outcomes. Hepatology. 2011 Sep 2;54(3):820-8. doi: 10.10 — View Citation

Xu L, Gong Y, Wang B, Shi K, Hou Y, Wang L, Lin Z, Han Y, Lu L, Chen D, Lin X, Zeng Q, Feng W, Chen Y. Randomized trial of autologous bone marrow mesenchymal stem cells transplantation for hepatitis B virus cirrhosis: regulation of Treg/Th17 cells. J Gast — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline alanine aminotransferase at 6 months	alanine aminotransferase (ALT)	baseline and 6 months after treatment	No
Primary	Change from baseline aspartate aminotransferase at 6 months	aspartate aminotransferase (AST)	baseline and 6 months after treatment	No
Primary	Change from baseline total bilirubin at 6 months	total bilirubin (TBil)	baseline and 6 months after treatment	No
Primary	Change from baseline direct bilirubin at 6 months	direct bilirubin (DBil)	baseline and 6 months after treatment	No
Primary	Change from baseline total bile acid at 6 months	total bile acid (TBA)	baseline and 6 months after treatment	No
Primary	Change from baseline albumin at 6 months	albumin (ALB)	baseline and 6 months after treatment	No
Primary	Change from baseline prothrombin time at 6 months	prothrombin time (PT),	baseline and 6 months after treatment	No
Primary	Change from baseline international normalized ratio at 6 months	international normalized ratio (INR)	baseline and 6 months after treatment	No
Primary	Change from baseline white blood cell at 6 months	white blood cell (WBC)	baseline and 6 months after treatment	No
Primary	Change from baseline platelet at 6 months	platelet (PLT)	baseline and 6 months after treatment	No
Secondary	Change from baseline liver density at 6 months	Low density, medium density, high density tested by abdominal B ultrasound/CT/MRI	baseline and 6 months after treatment	No
Secondary	Change from baseline liver size at 6 months	Enlarged size, normal size, shrunken size tested by abdominal B ultrasound/CT/MRI	baseline and 6 months after treatment	No
Secondary	Change from baseline spleen thickness at 6 months	tested by abdominal B ultrasound/CT/MRI	baseline and 6 months after treatment	No
Secondary	Incidence of adverse events that are related to treatment	Postoperative pyrexia, infection, liver cirrhosis, ascites, upper gastrointestinal hemorrhage, malignant tumors of liver and other organs	baseline and 6 months after treatment	Yes
Secondary	Number of participants that survive without developing disease		12 months after treatment	Yes
Secondary	Number of participants that survive with developing disease		12 months after treatment	Yes
Secondary	Number of participants that die after treatment		12 months after treatment	Yes