Human Umbilical Cord Mesenchymal Stem Cell Transplantation for The Treatment of Acute-on-Chronic Liver Failure

NCT ID: NCT05985863

Last Updated: 2024-05-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-30
• Study Completion Date: 2028-12-30

Brief Summary

This study is a randomized double-blind placebo-controlled multicenter clinical trial to evaluate the safety and efficacy of human umbilical cord mesenchymal stem cell (UC-MSC) transplantation for the treatment of acute-on-chronic liver failure (ACLF). UC-MSC therapy may improve the clinical outcomes of patients with ACLF. The trial would provide scientific evidence for UC-MSC transplantation as a potential treatment for ACLF.

Detailed Description

Acute-on-chronic liver failure (ACLF) has been proposed to define a distinct syndrome which is characterized by an intense systemic inflammatory response, single- or multiple organ system failures, and high 28-day mortality. Current treatments for liver failure are still limited, and liver transplantation remains the only available approach to improve survival but is restricted by a shortage of organ resources, rejection after transplantation, and heavy financial costs. In the past decade, a series of new applications based on mesenchymal stem cell (MSC) therapy have been studied as an alternative interventional method for chronic liver diseases. This randomized double-blind placebo-controlled multicenter clinical trial is aimed at determining the safety and clinical efficacy of UC-MSC transfusions in ACLF patients.

A total of 150 ACLF patients would be enrolled,100patients would be assigned to the MSC intervention group and the other 50 patients would be assigned to the placebo control group. This trial is two-stage randomized designed. At the first stage, the patients would be randomized into two groups, the placebo short control group would receive standard medical treatment plus 3 times placebo (at week0, week1 and week2), while the MSC short treatment group would receive standard medical treatment plus 3 times hUC-MSC (1.5×10^8, Peripheral IV, at week0, week1 and week2). The two groups would be followed up for 2 weeks, and unblinding would be conducted at week4. At the second stage, the survived patients of the MSC short treatment group would be further randomized and blinded into another two groups. The MSC Prolonged treatment group would receive another 2 times hUC-MSC (1.5×10^8, Peripheral IV, at week4 and week5), while the MSC Prolonged control group would receive 2 times placebo (at week4 and week5).

Transplantation free survival rate and incidence of treatment-emergent adverse events would be the primary outcomes, and other outcomes such as international normalized ratio (INR), total bilirubin (TBIL, mg/dL), serum albumin (ALB, g/L), blood urea nitrogen (BUN, mmol/l), the model for end-stage liver disease(MELD) score and child-turcotte-pugh(CTP) score would also be measured.

Conditions

Acute-On-Chronic Liver Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group Control

standard medical treatment+Placebo(5% human serum albumin in 0.9% saline, at week0, week1 and week2)

Group Type: PLACEBO_COMPARATOR

standard medical treatment

Intervention Type: DRUG

standard medical treatment for ACLF

Placebo

Intervention Type: DRUG

5% human serum albumin in 0.9% saline (at week0, week1 and week2)

Group MSC-1

Patients received standard medical treatment and infusions of hUC-MSC(1.5×10\^8) via peripheral veins once a week for 3 timess(at week0, week1, and week2).

Group Type: EXPERIMENTAL

standard medical treatment

Intervention Type: DRUG

standard medical treatment for ACLF

hUC-MSC

Intervention Type: DRUG

hUC-MSC (1.5×10\^8 cells/time, Peripheral IV, at week0, week1 and week2)

Group MSC-2

Patients in Group MSC-1 received standard medical treatment and infusions of hUC-MSC(1.5×10\^8) via peripheral veins once a week for another 2 timess(at week4 and week5).

Group Type: EXPERIMENTAL

standard medical treatment

Intervention Type: DRUG

standard medical treatment for ACLF

hUC-MSC

Intervention Type: DRUG

hUC-MSC (1.5×10\^8 cells/time, Peripheral IV, at week0, week1 and week2)

hUC-MSC_Prolonged

Intervention Type: DRUG

hUC-MSC (1.5×10\^8 cells/time, Peripheral IV, at week4 and week5)

Interventions

standard medical treatment

standard medical treatment for ACLF

Intervention Type: DRUG

Placebo

5% human serum albumin in 0.9% saline (at week0, week1 and week2)

Intervention Type: DRUG

hUC-MSC

hUC-MSC (1.5×10\^8 cells/time, Peripheral IV, at week0, week1 and week2)

Intervention Type: DRUG

hUC-MSC_Prolonged

hUC-MSC (1.5×10\^8 cells/time, Peripheral IV, at week4 and week5)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 18 years old ≤ age ≤ 70 years old, gender is not limited.

2. Meet the APASL definition of ACLF: acute liver injury in patients with previously diagnosed or undiagnosed chronic liver disease or cirrhosis, manifested as jaundice (total bilirubin levels of 5 mg/dl or more) and coagulopathy (INR of 1.5 or more, or prothrombin activity of less than 40%） complicated within 4 weeks by clinical ascites, encephalopathy, or both.

3. Willing to sign the informed consent form.

Exclusion Criteria

1. Patients with acute kidney injury, upper gastrointestinal hemorrhage, hepatic encephalopathy above grade II (inclusive) or uncontrolled infection at baseline;

2. Before the onset of liver failure, the previous indicators of the patient included PLT<50×10^9/L or Child-Pugh score>9;

3. Combined with liver cancer or other malignant tumors;

4. Patients with previous liver transplantation or planned liver transplantation within 3 months;

5. Severe organic disease of primary extrahepatic organs;

6. Those who have a history of venous thrombosis or pulmonary embolism are judged by the investigator to be ineligible to participate in this trial;

7. Pregnant, breastfeeding women or those who plan to have a baby in the near future;

8. Those who are highly allergic or have a history of severe allergies;

9. Those who have received immunosuppressant and immune enhancer treatment within 1 month;

10. Drug abuse in the past 5 years;

11. Alcohol withdrawal symptoms;

12. A history of severe mental disorders within 24 months before screening, including uncontrolled major depression or controlled or uncontrolled psychosis;

13. Those who have participated or are participating in other clinical trials within three months before screening, or have previously received stem cell therapy;

14. Other conditions that the investigator thinks that the patient is not suitable to participate in this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shulan (Hang Zhou) Hospital

UNKNOWN

Sponsor Role: collaborator

BeijingYouan Hospital

UNKNOWN

Sponsor Role: collaborator

Shenzhen Third People's Hospital

OTHER

Sponsor Role: collaborator

Shen Zhen Wingor Biotechnology CO. LTD

INDUSTRY

Sponsor Role: collaborator

Beijing 302 Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shi Ming

Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ming Shi, PhD

Role: PRINCIPAL_INVESTIGATOR

the Fifth Medical Center, Chinese PLA General Hospital

Locations

the Fifth Medical Center, Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tao Yang, MD

Role: CONTACT

y_t_0321@163.com

86-010-66933333

Yanhu Wang, MM

Role: CONTACT

2440477984@qq.com

86-010-66933328

Facility Contacts

Tao Yang, MD

Role: primary

y_t_0321@163.com

010-66933333

Mengyao Li, MB

Role: backup

qianlimengyao@163.com

010-66933333

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Other Identifiers

2022YFC2304402

Identifier Type: -

Identifier Source: org_study_id