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

Last updated: May 6, 2024
Sponsor: Beijing 302 Hospital
Overall Status: Active - Recruiting

Phase

1/2

Condition

Liver Failure

Primary Biliary Cholangitis

Liver Disease

Treatment

standard medical treatment

hUC-MSC at week2

hUC-MSC at week1

Clinical Study ID

NCT05985863
2022YFC2304402
  • Ages 18-70
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 previouslydiagnosed 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, orprothrombin activity of less than 40%） complicated within 4 weeks by clinical ascites,encephalopathy, or both.
  3. Willing to sign the informed consent form.

Exclusion

Exclusion Criteria:

  1. Patients with acute kidney injury, upper gastrointestinal hemorrhage, hepaticencephalopathy above grade II (inclusive) or uncontrolled infection at baseline;
  2. Before the onset of liver failure, the previous indicators of the patient includedPLT<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 3months;
  5. Severe organic disease of primary extrahepatic organs;
  6. Those who have a history of venous thrombosis or pulmonary embolism are judged by theinvestigator 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 1month;
  10. Drug abuse in the past 5 years;
  11. Alcohol withdrawal symptoms;
  12. A history of severe mental disorders within 24 months before screening, includinguncontrolled major depression or controlled or uncontrolled psychosis;
  13. Those who have participated or are participating in other clinical trials within threemonths before screening, or have previously received stem cell therapy;
  14. Other conditions that the investigator thinks that the patient is not suitable toparticipate in this study.

Study Design

Total Participants: 150
Treatment Group(s): 16
Primary Treatment: standard medical treatment
Phase: 1/2
Study Start date:
September 30, 2023
Estimated Completion Date:
December 30, 2028

Study 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.

Connect with a study center

  • the Fifth Medical Center, Chinese PLA General Hospital

    Beijing, Beijing 100039
    China

    Active - Recruiting

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