Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
PHASE2
16 participants
INTERVENTIONAL
2021-09-30
2024-07-21
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Umbilical Cord Mesenchymal Stem Cells Infusion Via Hepatic Artery in Cirrhosis Patients
NCT01224327
Human Umbilical Cord Mesenchymal Stem Cells Transplantation for Patients With Decompensated Liver Cirrhosis
NCT01342250
Injectable Collagen Scaffold™ Combined With HUC-MSCs Transplantation for Patients With Decompensated Cirrhosis
NCT02786017
MSC-EVs in Acute/ Acute-on-Chronic Liver Failure After Liver Transplantation
NCT06825572
Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation for Children Suffering From Biliary Atresia
NCT04522869
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
In 2013, European Association for the Study of Chronic Acute Liver Failure（EASL-CLIF） conducted a prospective multi-center EASL-CLIF Chronic Acute Liver Failure (CANONIC) study in 29 liver disease treatment centers in eight European countries, and proposed chronic liver failure-sequential organ failure assessment（CLIF-SOFA）score is used as the clinical diagnostic criteria for alcoholic and hepatitis B virus（HBV）related ACLF. According to the CLIF-SOFA score, the 90-day mortality rate of ACLF patients is as high as 51%, while that of non-ACLF patients is 10% \[3\]. The European CANONIC study also shows that systemic inflammation is the main driving force of multiple organ failure, which is a typical pathogenesis of ACLF patients with western liver cirrhosis \[4\]. For another, the current Asian ACLF diagnostic criteria is the Asia Pacific Association for the Study of Liver Diseases (APASL) criteria, which reached a consensus in 2009, and the guidelines were improved in 2014, but there is still a lack of multi-center, prospective evidence-based medical evidence to support . In 2016, led by the person in charge of this project, an oriental ACLF prospective multi-center observation cohort was established in China, which included 3970 ACLF high-risk patients, filling the gap in the natural course and mortality of oriental ACLF patients, and established a 90-day oriental ACLF diagnostic criteria for mortality \[5\]. The person in charge of this project also explored the pathophysiological mechanism of ACLF patients in areas with high prevalence of oriental HBV. The study showed that submassive hepatic necrosis is an important histological feature in ACLF patients with HBV-related cirrhosis. The systemic inflammatory response of multiple organ failure caused by parenchymal liver cells has a similar mechanism to that of western alcoholic ACLF \[6\]. Although the causes of ACLF type are not the same in the East and the West, the cohorts from the East and the West have confirmed the short-term high mortality rate of ACLF. Systemic inflammation, sub-large necrosis, and aseptic inflammation may all important reasons that lead to multiple organ failure and eventual death of ACLF patients.
Due to the high short-term mortality of ACLF and the limited liver source for liver transplantation, exploring new methods for the treatment of ACLF is a major issue facing clinical research. Mesenchymal stem cells have great application prospects in regenerative medicine because of their strong self-renewal, low immunogenicity, non-tumorigenicity and strong immune regulation ability\[7\]. Many previous documents have confirmed that mesenchymal stem cells in animal models can promote liver cell regeneration, resist inflammation, regulate local microenvironment and anti-fibrosis \[8-10\]. Among them, umbilical cord mesenchymal stem cells (UC-MSC) have attracted attention of researchers because they are easily obtained from the medical waste-the umbilical cord, are not invasive, and have high expansion capabilities in vitro \[11\]. The possible mechanism of UC-MSC in the treatment of end-stage liver disease is that it can repair the liver. At present, there are the following opinions: ① Cell rehabilitation. In the case of liver failure, MSC can differentiate into hepatocytes and play an alternative therapeutic effect. A large number of studies have shown that MSC can be differentiated into functional hepatocytes in different inducing factors and culture systems in vitro, capable of storing glycogen and urea synthesis. Function; ②Immune regulation. Studies have shown that MSC can regulate immune cells by secreting a variety of cytokines in the body, and play an immunomodulatory effect; ③Anti-fibrosis. MSC can induce hepatic stellate cell apoptosis or inhibit its activation, and can secrete anti-fibrotic substances such as granulocyte colony stimulating factor and matrix metallopeptidase 9（MMP-9）to reduce the deposition of extracellular matrix and inhibit the formation of liver fibrosis.
According to the results of a single-center clinical trial published by the Third Affiliated Hospital of Sun Yat-sen University in the previous period, there were no serious adverse reactions at 6 hours and 72 weeks after intravenous infusion of MSCs. The dose was (1-6)\*10\^7 cells/time for 4 times, confirming the safety and effectiveness of both low-dose and high-dose treatments. Another open clinical trial of Beijing 302 Hospital used mesenchymal stem cells at a dose of 5\*10\^5 cells/kg (based on the patient's weight of 60kg, the dose was 3\*10\^7 cells/time), excluded severe ACLF patients accompanied by severe infections and other sever complications. In addition, previous pharmacokinetic tests showed that the half-life of mesenchymal stem cells in animals is 3 days.
Therefore, this research plans to carry out a single-center open clinical trial to confirm the safety of umbilical cord-derived mesenchymal stem cells in the treatment of ACLF, and provide stronger clinical evidence for the safety of UC-MSCs in the treatment of ACLF.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
low dose
hUC-MSCs 4\*10\^5/kg/each time
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)
The hUC-MSCs were injected intravenously on the 1, 4, 7 and 10 days after patients recruitment. The treatment doses include low dose: 4\*10\^5 cells/kg/each time, and medium dose: 8\*10\^5 cells/kg/each time, high dose 12\*10\^5 cells/kg/each time. After 3 groups of patients were enrolled, the group with appropriate safety and effectiveness was selected and the other 4 subjects were included.
middle dose
hUC-MSCs 8\*10\^5/kg/each time
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)
The hUC-MSCs were injected intravenously on the 1, 4, 7 and 10 days after patients recruitment. The treatment doses include low dose: 4\*10\^5 cells/kg/each time, and medium dose: 8\*10\^5 cells/kg/each time, high dose 12\*10\^5 cells/kg/each time. After 3 groups of patients were enrolled, the group with appropriate safety and effectiveness was selected and the other 4 subjects were included.
high dose
hUC-MSCs 12\*10\^5/kg/each time
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)
The hUC-MSCs were injected intravenously on the 1, 4, 7 and 10 days after patients recruitment. The treatment doses include low dose: 4\*10\^5 cells/kg/each time, and medium dose: 8\*10\^5 cells/kg/each time, high dose 12\*10\^5 cells/kg/each time. After 3 groups of patients were enrolled, the group with appropriate safety and effectiveness was selected and the other 4 subjects were included.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)
The hUC-MSCs were injected intravenously on the 1, 4, 7 and 10 days after patients recruitment. The treatment doses include low dose: 4\*10\^5 cells/kg/each time, and medium dose: 8\*10\^5 cells/kg/each time, high dose 12\*10\^5 cells/kg/each time. After 3 groups of patients were enrolled, the group with appropriate safety and effectiveness was selected and the other 4 subjects were included.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. . A history of chronic liver disease, chronic acute liver failure (ACLF) caused by various causes, 1-2 organ failure (ACLF diagnosis is based on the European EASL diagnostic criteria, and the organ failure criteria is based on CLIF-OF);
3. . The patient or adult family members agree to participate in this study and sign an informed consent form;
Exclusion Criteria
1. Those who intend to undergo artificial liver treatment;
2. Those who have received liver transplantation and any form of stem cell therapy;
3. Malignant tumors in or outside the liver; or imaging findings suggest malignant mass in the liver or tuberculosis;
4. Complicated with severe autoimmune diseases; combined with severe cardiopulmonary insufficiency; renal replacement therapy; Immunosuppressive therapy; HIV/tuberculosis infection; alcohol/drug addiction; participated in drug trials in the past 3 months;
5. Gastrointestinal bleeding or serious infection occurred in the past one month;
6. Pregnant and lactating women;
7. Those who do not have the ability to make independent judgments and have no direct adult family members to sign the informed consent form.
18 Years
70 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Hai Li
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Hai Li
chief physician of gastroenterological division
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Hai Li
Role: STUDY_DIRECTOR
Digestive Department of Renji Hospital,Shanghai Jiao Tong University School of Medicine
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Ren Ji Hospital, School of Medicine, Shanghai Jiao TongUniversity,
Shanghai, Shanghai Municipality, China
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, Gustot T, Saliba F, Domenicali M, Gerbes A, Wendon J, Alessandria C, Laleman W, Zeuzem S, Trebicka J, Bernardi M, Arroyo V; CANONIC Study Investigators of the EASL-CLIF Consortium. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013 Jun;144(7):1426-37, 1437.e1-9. doi: 10.1053/j.gastro.2013.02.042. Epub 2013 Mar 6.
Arroyo V, Moreau R, Jalan R. Acute-on-Chronic Liver Failure. N Engl J Med. 2020 May 28;382(22):2137-2145. doi: 10.1056/NEJMra1914900. No abstract available.
Claria J, Stauber RE, Coenraad MJ, Moreau R, Jalan R, Pavesi M, Amoros A, Titos E, Alcaraz-Quiles J, Oettl K, Morales-Ruiz M, Angeli P, Domenicali M, Alessandria C, Gerbes A, Wendon J, Nevens F, Trebicka J, Laleman W, Saliba F, Welzel TM, Albillos A, Gustot T, Benten D, Durand F, Gines P, Bernardi M, Arroyo V; CANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure (EF-CLIF). Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure. Hepatology. 2016 Oct;64(4):1249-64. doi: 10.1002/hep.28740. Epub 2016 Aug 25.
Gu WY, Xu BY, Zheng X, Chen J, Wang XB, Huang Y, Gao YH, Meng ZJ, Qian ZP, Liu F, Lu XB, Shang J, Li H, Wang SY, Sun X, Li H. Acute-on-Chronic Liver Failure in China: Rationale for Developing a Patient Registry and Baseline Characteristics. Am J Epidemiol. 2018 Sep 1;187(9):1829-1839. doi: 10.1093/aje/kwy083.
Li H, Xia Q, Zeng B, Li ST, Liu H, Li Q, Li J, Yang SY, Dong XJ, Gao T, Munker S, Liu Y, Liebe R, Xue F, Li QG, Chen XS, Liu Q, Zeng H, Wang JY, Xie Q, Meng QH, Wang JF, Mertens PR, Lammert F, Singer MV, Dooley S, Ebert MP, Qiu DK, Wang TL, Weng HL. Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation. J Hepatol. 2015 Jul;63(1):50-9. doi: 10.1016/j.jhep.2015.01.029. Epub 2015 Jan 31.
Galipeau J, Sensebe L. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. Cell Stem Cell. 2018 Jun 1;22(6):824-833. doi: 10.1016/j.stem.2018.05.004.
Arthur MJ. Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C. Gastroenterology. 2002 May;122(5):1525-8. doi: 10.1053/gast.2002.33367. No abstract available.
Cho KA, Lim GW, Joo SY, Woo SY, Seoh JY, Cho SJ, Han HS, Ryu KH. Transplantation of bone marrow cells reduces CCl4 -induced liver fibrosis in mice. Liver Int. 2011 Aug;31(7):932-9. doi: 10.1111/j.1478-3231.2010.02364.x. Epub 2010 Nov 24.
Aurich I, Mueller LP, Aurich H, Luetzkendorf J, Tisljar K, Dollinger MM, Schormann W, Walldorf J, Hengstler JG, Fleig WE, Christ B. Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers. Gut. 2007 Mar;56(3):405-15. doi: 10.1136/gut.2005.090050. Epub 2006 Aug 23.
Arutyunyan I, Elchaninov A, Makarov A, Fatkhudinov T. Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy. Stem Cells Int. 2016;2016:6901286. doi: 10.1155/2016/6901286. Epub 2016 Aug 29.
Xue R, Meng Q, Li J, Wu J, Yao Q, Yu H, Zhu Y. The assessment of multipotent cell transplantation in acute-on-chronic liver failure: a systematic review and meta-analysis. Transl Res. 2018 Oct;200:65-80. doi: 10.1016/j.trsl.2018.05.006. Epub 2018 Jun 23.
Xue R, Meng Q, Dong J, Li J, Yao Q, Zhu Y, Yu H. Clinical performance of stem cell therapy in patients with acute-on-chronic liver failure: a systematic review and meta-analysis. J Transl Med. 2018 May 10;16(1):126. doi: 10.1186/s12967-018-1464-0.
Chen B, Wang YH, Qian JQ, Wu DB, Chen EQ, Tang H. Human mesenchymal stem cells for hepatitis B virus-related acute-on-chronic liver failure: a systematic review with meta-analysis. Eur J Gastroenterol Hepatol. 2018 Oct;30(10):1224-1229. doi: 10.1097/MEG.0000000000001156.
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.
Lin BL, Chen JF, Qiu WH, Wang KW, Xie DY, Chen XY, Liu QL, Peng L, Li JG, Mei YY, Weng WZ, Peng YW, Cao HJ, Xie JQ, Xie SB, Xiang AP, Gao ZL. Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial. Hepatology. 2017 Jul;66(1):209-219. doi: 10.1002/hep.29189. Epub 2017 May 27.
Shi M, Zhang Z, Xu R, Lin H, Fu J, Zou Z, Zhang A, Shi J, Chen L, Lv S, He W, Geng H, Jin L, Liu Z, Wang FS. Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl Med. 2012 Oct;1(10):725-31. doi: 10.5966/sctm.2012-0034. Epub 2012 Oct 11.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
MSC-ACLF-1
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.