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

Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure

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

Study Overview

• Status: Unknown
• Conditions: Liver Failure, Acute on Chronic
• Intervention / Treatment: Biological: Mesenchymal Stem Cell

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 Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xiuli Cong, MD, PhD; Phone Number: +86 18512507567; Email: cong_xiuli@163.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Weikai Bioeng., Ltd.
      • Contact: Xiuli Cong, MD, PhD; Phone Number: +86 18512507567; Email: cong_xiuli@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 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]).
Experimental: 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.	Biological: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
survival rate	Number of participants alive	72 weeks after treatment

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Tianjin Weikai Bioeng., Ltd.
• Collaborators: Tianjin Nankai Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: February 18, 2019
• First Submitted That Met QC Criteria: March 2, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: mesenchymal stem cell
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure; Liver Failure, Acute
• Other Study ID Numbers: Tianjin Weikai Bioeng., Ltd

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No