Safety and Efficacy of Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure

Phase 1

• Conditions: Liver Failure, Acute on Chronic
• Interventions: Biological: Mesenchymal Stem Cell

• Registration Number: NCT03863002
• Lead Sponsor: Tianjin Weikai Bioeng., Ltd.

Brief Summary

Safety and Efficacy of Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure

Detailed Description

Acute-on-chronic liver failure (ACLF) which occurs in patients with chronic liver disease, is a serious live-threatening disease. Currently, the clinical management, such as liver protection, anti-virus medicine, and artificial liver support, has not significantly improve the outcomes, the mortality still remains over 50%. Liver transplantation is the only effective treatment of ACLF, but this therapy is limited by the shortage of donor organs, potential surgical complications, immunological rejection and high medical costs. Mesenchymal stem cell (MSC) is one of adult stem cells, which has been suggested to play a role in amelioration of liver disease, such as: trans-differentiation of MSCs into hepatocytes, immunomodulation, inhibition of fibrosis development, protective effects on hepatic cell and restoration of hepatic cell proliferation capacity.

Study Timeline

• Status Verified: 2018-04
• Study First Submitted: 2019-02-18
• Study First Submitted QC: 2019-03-02
• Study First Posted: 2019-03-05
• Last Update Submitted: 2019-03-18
• Last Update Posted: 2019-03-20
• Study Start: 2019-10-01
• Primary Completion: 2021-10-01
• Study Completion: 2022-10-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Informed consent
2. Meeting the definition of ACLF: patients with previously diagnosed or undiagnosed chronic liver disease acute decompensated within 4 weeks; significant GI symptom as such fatigue, jaundice; serum total bilirubin [TBil] ≥10 X the upper limit of normal; coagulopathy (international normalized ratio [INR] ≥1.5 or prothrombin activity [PTA] <40%); complicated within 4 weeks by ascites and/or encephalopathy as determined by physical examination.
3. Model for End-Stage Liver Disease (MELD) scores ranging 17-30, (MELD(i) = 0.957 × ln(Cr) + 0.378 × ln(bilirubin) + 1.120 × ln(INR) + 0.643);
4. Chronic liver disease with definitive etiology such as viral hepatitis, alcohol liver disease, drug induced liver injury or autoimmune liver diseases
5. Body weight ≥50kg

Exclusion Criteria

1. Serious complications in the previous 2 months (e.g., gastrointestinal bleeding: hemoglobin below 90g/L, serious infection such as sepsis, ascites ultrafiltration, and/or dialysis);
2. Malignant jaundice induced by obstructive jaundice or hemolytic jaundice;
3. Hepatocellular carcinoma (HCC) diagnosed by radiologic imaging and/or alpha fetoprotein (AFP);
4. Tumor diagnosed by ultrasound, CT, MR examination;
5. Moderate or severe chronic heart failure (NYHA III-IV), renal replacement therapy, severe chronic pulmonary disease (GOLD III-IV)
6. Extrahepatic cholestasis
7. Hepatic, portal and splenic vein thrombosis diagnosed by doppler ultrasound
8. Artificial liver support
9. Previous liver transplantation
10. Drug abuse in the past 5 years;
11. Mental disorders and/or has a family history of mental disorder.
12. HIV infection
13. Pregnant or breast-feeding females
14. Highly allergic
15. Patients can not cooperate or mobility
16. Enrolled in other clinical trials with 3 months
17. Patients who can not provide prior informed consent or refusal to participate

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mesenchymal Stem Cell	Mesenchymal Stem Cell	Mesenchymal Stem Cell (MSC): The MSC group received infusions of 1.0 to 10x10\^5cells/kg MSCs through the peripheral vein once a week for 4 weeks, in addition to SMT.

Primary Outcome Measures

Name	Time	Method
survival rate	72 weeks after treatment	Number of participants alive

Secondary Outcome Measures

Name	Time	Method
Adverse reactions	Week 1, 2, 4, 8, 12, 24, 36, 48	Number of participants with adverse reactions (e.g. fever, rash, and diarrhea )
ALB	Week 1, 2, 4, 8, 12, 24, 36, 48	Change of albumin (ALB) level as a maker of liver function
Liver failure-associated serious complications	Week 1, 2, 4, 8, 12, 24, 36, 48	Number of participants with liver failure-associated serious complications, such as infections, encephalopathy, gastrointestinal bleeding and HRS
White blood cell	Week 1, 2, 4, 8, 12, 24, 36, 48	Change of white blood cell count
Platelet	Week 1, 2, 4, 8, 12, 24, 36, 48	Change of platelet count
Hemoglobin	Week 1, 2, 4, 8, 12, 24, 36, 48	Change of hemoglobin level
Creatinine	Week 1, 2, 4, 8, 12, 24, 36, 48	Change of creatinine level as a surrogate marker of liver function
TBil	Week 1, 2, 4, 8, 12, 24, 36, 48	Change of total Bilirubin (TBil) level as a marker of liver function
ALT	Week 1, 2, 4, 8, 12, 24, 36, 48	Change of alanine aminotransferase (ALT) level as a marker of liver function
AFP	Week 1, 2, 4, 8, 12, 24, 36, 48	Change of alpha fetoprotein (AFP) level as a marker of liver function
Tumor formation	Week 1, 2, 4, 8, 12, 24, 36, 48	Number of participants with hepatocellular carcinoma or extrahepatic malignant tumors
INRs	Week 1, 2, 4, 8, 12, 24, 36, 48	Change of international normalized ratio (INRs) level as a marker of liver function
MELD scores	Week 1, 2, 4, 8, 12, 24, 36, 48	Model for End-Stage Liver Disease (MELD) score for assessing the severity of chronic liver disease is measured as absolute change to baseline score

Trial Locations

Locations (1)

Tianjin Weikai Bioeng., Ltd.; 🇨🇳 Tianjin, Tianjin, China