Clinical trial NCT03863002: Safety and Efficacy of Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure
Official title: Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Liver Failure, Acute on Chronic
Keywords: mesenchymal stem cell
Lead sponsor: Tianjin Weikai Bioeng., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Tianjin Nankai Hospital
First posted: 2019-03-05
Enrollment: 45
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: survival rate
timeFrame: 72 weeks after treatment
Secondary outcomes:
measure: Adverse reactions
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: White blood cell
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: Platelet
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: Hemoglobin
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: Creatinine
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: ALT
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: ALB
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: TBil
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: INRs
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: AFP
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: MELD scores
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: Tumor formation
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
measure: Liver failure-associated serious complications
timeFrame: Week 1, 2, 4, 8, 12, 24, 36, 48
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Weikai Bioeng., Ltd.
state: Tianjin
Study officials:
References: