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

NCT ID: NCT03863002

Last Updated: 2019-03-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-01
• Study Completion Date: 2022-10-01

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.

Conditions

Liver Failure, Acute on Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Medical Treatment

Standard Medical Treatment (SMT): All patients received SMT, including nutritional supplementation; administration of human serum albumin (serum albumin \<30 g/L), fresh frozen plasma (200-400 mL/day until the INR was \<1.5), S-adenosylmethionine (1.0 g/day); or anti-virus treatment for hepatic viruses-related cases, and appropriate treatment for complications such as infections (including of the respiratory tract, urinary tract, biliary tract, and digestive tract and spontaneous peritonitis), encephalopathy, gastrointestinal bleeding, and hepatorenal syndrome \[HRS\]).

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Mesenchymal Stem Cell

Intervention Type: BIOLOGICAL

Mesenchymal stem cell transplantation via peripheral vein: 1.0-10x10\^5 MSCs/kg body weight administered via peripheral vein at week 0, 1, 2, 3 weeks

Interventions

Mesenchymal Stem Cell

Mesenchymal stem cell transplantation via peripheral vein: 1.0-10x10\^5 MSCs/kg body weight administered via peripheral vein at week 0, 1, 2, 3 weeks

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Nankai Hospital

OTHER

Sponsor Role: collaborator

Tianjin Weikai Bioeng., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tianjin Weikai Bioeng., Ltd.

Tianjin, Tianjin Municipality, China

Countries

China

Central Contacts

Xiuli Cong, MD, PhD

Role: CONTACT

cong_xiuli@163.com

+86 18512507567

Facility Contacts

Xiuli Cong, MD, PhD

Role: primary

cong_xiuli@163.com

+86 18512507567

Other Identifiers

Tianjin Weikai Bioeng., Ltd

Identifier Type: -

Identifier Source: org_study_id