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

Liver Failure, Acute on Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03863002
• Other study ID #: Tianjin Weikai Bioeng., Ltd
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: October 1, 2019
• Est. completion date: October 1, 2022

Study information

• Verified date: April 2018
• Source: Tianjin Weikai Bioeng., Ltd.
• Contact: Xiuli Cong, MD, PhD
• Phone: +86 18512507567
• Email: cong_xiuli[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 45
• Est. completion date: October 1, 2022
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• End Stage Liver Disease
• Hepatic Insufficiency
• Liver Failure
• Liver Failure, Acute
• Liver Failure, Acute on Chronic

Intervention

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

Locations

Country	Name	City	State
China	Tianjin Weikai Bioeng., Ltd.	Tianjin	Tianjin

Sponsors (2)

Lead Sponsor	Collaborator
Tianjin Weikai Bioeng., Ltd.	Tianjin Nankai Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	survival rate	Number of participants alive	72 weeks after treatment
Secondary	Adverse reactions	Number of participants with adverse reactions (e.g. fever, rash, and diarrhea )	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	White blood cell	Change of white blood cell count	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	Platelet	Change of platelet count	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	Hemoglobin	Change of hemoglobin level	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	Creatinine	Change of creatinine level as a surrogate marker of liver function	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	ALT	Change of alanine aminotransferase (ALT) level as a marker of liver function	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	ALB	Change of albumin (ALB) level as a maker of liver function	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	TBil	Change of total Bilirubin (TBil) level as a marker of liver function	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	INRs	Change of international normalized ratio (INRs) level as a marker of liver function	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	AFP	Change of alpha fetoprotein (AFP) level as a marker of liver function	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	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
Secondary	Tumor formation	Number of participants with hepatocellular carcinoma or extrahepatic malignant tumors	Week 1, 2, 4, 8, 12, 24, 36, 48
Secondary	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