Clinical trial NCT05985863: Human Umbilical Cord Mesenchymal Stem Cell Transplantation for The Treatment of Acute-on-Chronic Liver Failure
Official title: Clinical Research of Human Umbilical Cord Mesenchymal Stem Cell Transplantation for The Treatment of Acute-on-Chronic Liver Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute-On-Chronic Liver Failure
Keywords: Mesenchymal Stem Cells
Acute-On-Chronic Liver Failure
Therapeutics
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
Collaborators: name: Shulan (Hang Zhou) Hospital
name: BeijingYouan Hospital
name: Shenzhen Third People's Hospital
name: Shen Zhen Wingor Biotechnology CO. LTD
First posted: 2023-08-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Transplantation free survival rate
timeFrame: week1, week2, week3, week4, week5, week8, week12, week24, week53
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: day0, day3, week1, week2, week3, week4, week5, week8, week12, week24, week53
Secondary outcomes:
measure: International Normalized Ratio (INR)
timeFrame: week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
measure: Concentration of Total Bilirubin (TBIL, mg/dL)
timeFrame: week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
measure: Concentration of Serum Albumin (ALB, g/L)
timeFrame: week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
measure: Concentration of Blood Urea Nitrogen (BUN, mmol/L)
timeFrame: week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53
measure: The Model for End-Stage Liver Disease(MELD) score
timeFrame: week-1, week1, week2, week4, week5, week12, week24, week53
measure: Child-Turcotte-Pugh(CTP) score
timeFrame: week-1, week1, week2, week4, week5, week12, week24, week53
Other outcomes:
Locations:
city: Beijing
country: China
facility: the Fifth Medical Center, Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: the Fifth Medical Center, Chinese PLA General Hospital
name: Ming Shi, PhD
role: PRINCIPAL_INVESTIGATOR
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