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

May 6, 2024 updated by: Shi Ming, Beijing 302 Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100039
        • Recruiting
        • the Fifth Medical Center, Chinese PLA General Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Group Control
standard medical treatment+Placebo(5% human serum albumin in 0.9% saline, at week0, week1 and week2)
Drug: standard medical treatment
standard medical treatment for ACLF
Drug: Placebo
5% human serum albumin in 0.9% saline (at week0, week1 and week2)
Experimental: 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).
Drug: standard medical treatment
standard medical treatment for ACLF
Drug: hUC-MSC
hUC-MSC (1.5×10^8 cells/time, Peripheral IV, at week0, week1 and week2)
Experimental: 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).
Drug: standard medical treatment
standard medical treatment for ACLF
Drug: hUC-MSC
hUC-MSC (1.5×10^8 cells/time, Peripheral IV, at week0, week1 and week2)
Drug: hUC-MSC_Prolonged
hUC-MSC (1.5×10^8 cells/time, Peripheral IV, at week4 and week5)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Transplantation free survival rate
Time Frame: week1, week2, week3, week4, week5, week8, week12, week24, week53
Transplantation free survival rate of ACLF patients.
week1, week2, week3, week4, week5, week8, week12, week24, week53
Incidence of Treatment-Emergent Adverse Events
Time Frame: day0, day3, week1, week2, week3, week4, week5, week8, week12, week24, week53
Safety and Tolerability of UC-MSCs transplantation.
day0, day3, week1, week2, week3, week4, week5, week8, week12, week24, week53

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
International Normalized Ratio (INR)
Time Frame: week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
INR was introduced as a standardized reporting mechanism allowing comparisons across laboratories and patients. Consensus guidelines recommend that INR ≥ 1.5 can be used as a threshold, and current recommendations for targeting an INR of < 1.5 were based on studies across all surgical disciplines.
week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
The Model for End-Stage Liver Disease(MELD) score
Time Frame: week-1, week1, week2, week4, week5, week12, week24, week53
R = 3.8×ln [TBiL (mg/dl)] +11.2×ln (INR) +9.6×ln [Cr (mg/dl)] +6.4× (Cause: biliary or alcoholic is 0, other is 1), the result is taken as an integer. Studies have shown that the optimal critical value of MELD score to judge the short-term prognosis of ACLF patients is 30, and when MELD score is greater than 30, the case fatality rate of patients within 3 months is significantly increased.
week-1, week1, week2, week4, week5, week12, week24, week53
Concentration of Total Bilirubin (TBIL, mg/dL)
Time Frame: week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
Total bilirubin refers to the concentration of bilirubin in a patient's blood sample, which is automatically measured by the laboratories in accordance with standard operating procedures. APASL defines ACLF as "an acute hepatic insult manifesting as jaundice (Serum Bilirubin ≥ 5 mg/dL) and coagulopathy (international normalized ratio [INR] ≥ 1.5) complicated within 4 weeks by clinical ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease/cirrhosis, that is associated with a high 28-day mortality."
week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
Concentration of Serum Albumin (ALB, g/L)
Time Frame: week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
Serum albumin refers to the concentration of albumin in a patient's serum, which is automatically measured by the laboratory in accordance with standard operating procedures. Serum albumin is an independent protective factor for 30-day prognosis in ACLF patients.
week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
Concentration of Blood Urea Nitrogen (BUN, mmol/L)
Time Frame: week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
Blood urea nitrogen refers to the concentration of urea nitrogen in a patient's blood sample. Blood urea nitrogen is a commonly used indicator of renal function in clinic.
week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
Child-Turcotte-Pugh(CTP) score
Time Frame: week-1, week1, week2, week4, week5, week12, week24, week53
CTP score is currently the most commonly used model to evaluate liver reserve function and prognosis in patients with cirrhosis. This model evaluates liver function based on HE grade, degree of abdominal fluid accumulation, bilirubin (TBiL), albumin (Alb) and prothrombin time (PT). The score ranges from 0 to 15, with the higher the score, the worse the prognosis.
week-1, week1, week2, week4, week5, week12, week24, week53

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing 302 Hospital

Collaborators

Shenzhen Third People's Hospital
Shulan (Hang Zhou) Hospital
BeijingYouan Hospital
Shen Zhen Wingor Biotechnology CO. LTD

Investigators

  • Principal Investigator: Ming Shi, PhD, the Fifth Medical Center, Chinese PLA General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2023

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 30, 2028

Study Registration Dates

First Submitted

July 24, 2023

First Submitted That Met QC Criteria

August 3, 2023

First Posted (Actual)

August 14, 2023

Study Record Updates

Last Update Posted (Actual)

May 7, 2024

Last Update Submitted That Met QC Criteria

May 6, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022YFC2304402

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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