Clinical trial NCT02943707: Autologous Bone Marrow Stem Cells Infusion for the Treatment of Liver Diseases.
Official title: Autologous Bone Marrow Stem Cells Infusion for the Treatment of Liver Diseases.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Liver Diseases
Keywords: liver diseases
Bone Marrow Cell Transplantation
Lead sponsor: Wenzhou Medical University
Sponsor class: OTHER
First posted: 2016-10-25
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline alanine aminotransferase at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline aspartate aminotransferase at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline total bilirubin at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline direct bilirubin at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline total bile acid at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline albumin at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline prothrombin time at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline international normalized ratio at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline white blood cell at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline platelet at 6 months
timeFrame: baseline and 6 months after treatment
Secondary outcomes:
measure: Change from baseline liver density at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline liver size at 6 months
timeFrame: baseline and 6 months after treatment
measure: Change from baseline spleen thickness at 6 months
timeFrame: baseline and 6 months after treatment
measure: Incidence of adverse events that are related to treatment
timeFrame: baseline and 6 months after treatment
measure: Number of participants that survive without developing disease
timeFrame: 12 months after treatment
measure: Number of participants that survive with developing disease
timeFrame: 12 months after treatment
measure: Number of participants that die after treatment
timeFrame: 12 months after treatment
Other outcomes:
Locations:
city: Wenzhou
country: China
facility: the First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Wenzhou Medical University
name: yongping chen
role: STUDY_CHAIR
References:
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.
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 Gastroenterol Hepatol. 2014 Aug;29(8):1620-8. doi: 10.1111/jgh.12653.
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: 10.1002/hep.24434. Epub 2011 Jul 14.
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: 10.5812/hepatmon.32498. eCollection 2015 Dec.
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+ Cells in Patients With Decompensated Cirrhosis: A Double-Blind Randomized Controlled Trial. Stem Cells Transl Med. 2016 Jan;5(1):87-94. doi: 10.5966/sctm.2015-0004. Epub 2015 Dec 10.
citation: 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: 10.1016/j.imlet.2014.10.021. Epub 2014 Oct 28.