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Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis

Primary Purpose

Decompensated Cirrhosis

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

UC-MSCs

Saline containing 1% Human serum albumin（solution without UC-MSCs）

About this trial

This is an interventional treatment trial for Decompensated Cirrhosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Willing to provide written informed consent;
Aged 18 to 75 years (including 18 and 75 years), male or female;
Patients diagnosed with decompensated liver cirrhosis based on clinical findings, laboratory tests, imaging findings and/or representative pathological findings (decompensated liver cirrhosis is defined as the occurrence of at least one serious complication, including esophageal and gastric varices bleeding, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis and other serious complications);
Child-Turcotte-Pugh (CTP) score 7 to 12 points.

Exclusion Criteria:

Appearance of active variceal bleeding, overt hepatic encephalopathy (HE), refractory ascites or hepatorenal syndrome within 1 month prior to screening visit.
Uncontrolled severe infection within 2 weeks of screening.
Hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening.
Patients with hepatitis B virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HBV for less than 12 months.
Patients with hepatitis C virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HCV for less than 12 months.
Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6 months.
Trans-jugular intrahepatic portosystemic shunts (TIPS) insertion within 6 months prior to study inclusion.
Active drinkers with alcohol-related decompensated cirrhosis are unwilling to stop alcohol abuse after inclusion.
Severe jaundice (serum total bilirubin level ≥ 170μmol/L); Significant renal insufficiency (serum creatinine ≥ 1.2 times upper normal limit); Severe electrolyte abnormality (serum sodium level < 125 mmol/L); Severe leukopenia (white blood cell count < 1 × 10E9/L).
Patients with biliary obstruction, hepatic vein, portal vein, splenic vein thrombosis and portal vein spongiosis.
Patients with surgical history such as splenic cut-off flow and portal body shunt.
Patients with confirmed or suspected malignancies.
Patients with a prior history of major organ transplantation or complicated with significant disease of heart, lung, kidney, blood, endocrine and other systems.
Drug abuse, drug dependence and patients who receive methadone treatment or with psychosis.
HIV seropositivity.
Those who have received blood transfusion or other blood products within 1 month prior to screening visit.
Pregnancy, lactation or with recent fertility plan.
Highly allergic or have a history of severe allergies.
Participants in other clinical trials within the last 3 months.
Any other clinical condition which the investigator considers would make the patient unsuitable for the trial.

Sites / Locations

The First Hospital of Lanzhou University
Hainan hospital of Chinese PLA General Hospital
Renmin Hospital of Wuhan University
Shanghai Changzheng Hospital
Beijing 302 HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)

Placebo

Arm Description

standard of care (SOC) plus UC-MSCs

SOC plus placebo.

Outcomes

Primary Outcome Measures

Change in Model for End-Stage Liver Disease (MELD) score from baseline to 24th week

The Model for End-stage Liver Disease (MELD) is a scoring system that evaluates the liver function reserve and prognosis of patients with chronic liver disease by creatinine, international normalized ratio (INR), and bilirubin-conjugated cirrhosis etiology. The MELD score is calculated by the formula: R = 9.6 × ln (creatinine mg/dl) + 3.8 × ln (bilirubin mg/dl) + 11.2 × ln (INR) + 6.4 × etiology, and the results are taken as integers. ( 0 for cholestatic and alcoholic cirrhosis and 1 for other causes of cirrhosis such as viruses).

Secondary Outcome Measures

Change in MELD score from baseline to 48 weeks

Incidence of each complication associated with decompensated cirrhosis

liver transplant-free survival

Incidence of liver failure

plasma albumin (ALB)

total bilirubin (TBIL)

serum cholinesterase (CHE)

prothrombin activity (PA)

Child-Turcotte-Pugh (CTP) score

Child-Turcotte-Pugh (CTP) score is a scoring system that evaluates the liver function.

EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)

ChronicLiver Disease Questionnaire (CLDQ)

Incidence of liver cancer

Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events

Full Information

NCT ID

NCT05121870

First Posted

October 17, 2021

Last Updated

November 3, 2021

Sponsor

Beijing 302 Hospital

Collaborators

Shanghai Changzheng Hospital, LanZhou University, Renmin Hospital of Wuhan University, Chinese PLA General Hospital, VCANBIO Cell & Gene Engineering Corporation, Ltd

1. Study Identification

Unique Protocol Identification Number

NCT05121870

Brief Title

Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis

Official Title

A Randomized, Double-blind, Placebo-controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Human Umbilical Cord-derived Mesenchymal Stem Cells Combined With Standard Therapy in Patients With Decompensated Cirrhosis

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Recruiting

Study Start Date

September 1, 2021 (Actual)

Primary Completion Date

June 30, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Beijing 302 Hospital

Collaborators

Shanghai Changzheng Hospital, LanZhou University, Renmin Hospital of Wuhan University, Chinese PLA General Hospital, VCANBIO Cell & Gene Engineering Corporation, Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Decompensated cirrhosis has a high overall mortality rate. There is a large unmet need for safe and alternative therapeutic potions. This clinical trial is to inspect the efficiency and safety of mesenchymal stem cells (MSCs) therapy for decompensated cirrhosis.

Detailed Description

Decompensated cirrhosis has a high overall mortality rate. Liver transplantation is still the most effective treatment for decompensated cirrhosis. However, the shortage of matched liver sources, high costs, and rejection after liver transplantation restrict the development of liver transplantation. Mesenchymal stem cells (MSC) are a kind of pluripotent stem cells belonging to mesoderm, which mainly exist in connective tissue and organ interstitium. At present, MSC can be isolated and prepared from bone marrow, fat, synovium, bone, muscle, lung, liver, pancreas and amniotic fluid and umbilical cord blood . Due to its wide range of sources and self-proliferation and differentiation ability, MSCs have therapeutic potential for many diseases, including acute and chronic liver diseases. In recent years, our team has carried out a series of clinical trials using umbilical cord-derived MSCs to treat patients with end-stage liver disease, decompensated cirrhosis, primary biliary cholangitis, and status after liver transplantation and found that MSCs therapy can significantly improve patient liver function, reduce post-transplantation rejection, reduce complications, improve quality of life, and improve survival. Other investigators have also found in clinical trials with MSCs from different sources that treatment with MSCs can improve MELD scores or liver function levels to varying degrees. However, some studies have found no significant difference between the treatment group and the control group, and MSCs may differentiate into hepatic stellate cells and have the risk of promoting liver fibrosis, it is believed that MSCs do not favor the improvement of liver function in these studies. Therefore, the therapeutic effects of MSCs need to be further validated by larger multicenter randomized controlled clinical trials. The investigators will do a prospective, double-blind, multicentre, randomised trial to assess treatment with three intravenous doses of MSCs compared with placebo. 240 decompensated cirrhosis patients will be recruited in China.120 patients will receive i.v. transfusion 3 times of MSCs (6.0×10E7 cells per time) and the standard of care as the treated group. In addition, the 120 patients will receive placebo and standard of care as control group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Decompensated Cirrhosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Randomized, double-blind, placebo-controlled, multicenter study

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)

Arm Type

Experimental

Arm Description

standard of care (SOC) plus UC-MSCs

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

SOC plus placebo.

Intervention Type

Biological

Intervention Name(s)

UC-MSCs

Intervention Description

3 does of UC-MSCs(6.0×10E7cells per time) intravenously at week 0, week 4, week 8.

Intervention Type

Biological

Intervention Name(s)

Saline containing 1% Human serum albumin（solution without UC-MSCs）

Intervention Description

3 does of placebo intravenously at week 0, week 4, week 8.

Primary Outcome Measure Information:

Title

Change in Model for End-Stage Liver Disease (MELD) score from baseline to 24th week

Description

Time Frame

at 24th week

Secondary Outcome Measure Information:

Title

Change in MELD score from baseline to 48 weeks

Time Frame

up to 48 weeks

Title

Incidence of each complication associated with decompensated cirrhosis

Time Frame

up to 48 weeks

Title

liver transplant-free survival

Time Frame

up to 48 weeks

Title

Incidence of liver failure

Time Frame

up to 48 weeks

Title

plasma albumin (ALB)

Time Frame

up to 48 weeks

Title

total bilirubin (TBIL)

Time Frame

up to 48 weeks

Title

serum cholinesterase (CHE)

Time Frame

up to 48 weeks

Title

prothrombin activity (PA)

Time Frame

up to 48 weeks

Title

Child-Turcotte-Pugh (CTP) score

Description

Child-Turcotte-Pugh (CTP) score is a scoring system that evaluates the liver function.

Time Frame

up to 48 weeks

Title

EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)

Time Frame

up to 48 weeks

Title

ChronicLiver Disease Questionnaire (CLDQ)

Time Frame

up to 48 weeks

Title

Incidence of liver cancer

Time Frame

up to 48 weeks

Title

Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events

Time Frame

up to 48weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Willing to provide written informed consent; Aged 18 to 75 years (including 18 and 75 years), male or female; Patients diagnosed with decompensated liver cirrhosis based on clinical findings, laboratory tests, imaging findings and/or representative pathological findings (decompensated liver cirrhosis is defined as the occurrence of at least one serious complication, including esophageal and gastric varices bleeding, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis and other serious complications); Child-Turcotte-Pugh (CTP) score 7 to 12 points. Exclusion Criteria: Appearance of active variceal bleeding, overt hepatic encephalopathy (HE), refractory ascites or hepatorenal syndrome within 1 month prior to screening visit. Uncontrolled severe infection within 2 weeks of screening. Hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening. Patients with hepatitis B virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HBV for less than 12 months. Patients with hepatitis C virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HCV for less than 12 months. Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6 months. Trans-jugular intrahepatic portosystemic shunts (TIPS) insertion within 6 months prior to study inclusion. Active drinkers with alcohol-related decompensated cirrhosis are unwilling to stop alcohol abuse after inclusion. Severe jaundice (serum total bilirubin level ≥ 170μmol/L); Significant renal insufficiency (serum creatinine ≥ 1.2 times upper normal limit); Severe electrolyte abnormality (serum sodium level < 125 mmol/L); Severe leukopenia (white blood cell count < 1 × 10E9/L). Patients with biliary obstruction, hepatic vein, portal vein, splenic vein thrombosis and portal vein spongiosis. Patients with surgical history such as splenic cut-off flow and portal body shunt. Patients with confirmed or suspected malignancies. Patients with a prior history of major organ transplantation or complicated with significant disease of heart, lung, kidney, blood, endocrine and other systems. Drug abuse, drug dependence and patients who receive methadone treatment or with psychosis. HIV seropositivity. Those who have received blood transfusion or other blood products within 1 month prior to screening visit. Pregnancy, lactation or with recent fertility plan. Highly allergic or have a history of severe allergies. Participants in other clinical trials within the last 3 months. Any other clinical condition which the investigator considers would make the patient unsuitable for the trial.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lei Shi, MD,PhD

Phone

86-10-66949623

shilei302@126.com

First Name & Middle Initial & Last Name or Official Title & Degree

Fu-Sheng Wang, MD,PhD

Phone

86-10-66933332

fswang302@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fu-Sheng Wang, MD, PhD

Organizational Affiliation

Beijing 302 Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

The First Hospital of Lanzhou University

City

Lanzhou

State/Province

Gansu

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xun Li

lix@lzu.edu.cn

Facility Name

Hainan hospital of Chinese PLA General Hospital

City

Sanya

State/Province

Hainan

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ya-Li Zhao

zhaoyl301@163.com

Facility Name

Renmin Hospital of Wuhan University

City

Wuhan

State/Province

Hubei

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ying-an Jiang

jiangya_cn@aliyun.com

Facility Name

Shanghai Changzheng Hospital

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200003

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wei-Fen Xie, MD, PhD

weifenxie@medmail.com.cn

Facility Name

Beijing 302 Hospital

City

Beijing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lei Shi, MD,PhD

Phone

86-10-66949623

shilei302@126.com

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

After approval from the steering committee and the Human Genetic Resources Administration of China, this trial data can be shared with qualifying researchers who submit a proposal with a valuable research question. A contract should be signed.

Learn more about this trial

Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis

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