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Safety and Efficacy of Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure

Primary Purpose

Liver Failure, Acute on Chronic

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Mesenchymal Stem Cell

About this trial

This is an interventional treatment trial for Liver Failure, Acute on Chronic focused on measuring mesenchymal stem cell

Eligibility Criteria

16 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Informed consent
Meeting the definition of ACLF: patients with previously diagnosed or undiagnosed chronic liver disease acute decompensated within 4 weeks; significant GI symptom as such fatigue, jaundice; serum total bilirubin [TBil] ≥10 X the upper limit of normal; coagulopathy (international normalized ratio [INR] ≥1.5 or prothrombin activity [PTA] <40%); complicated within 4 weeks by ascites and/or encephalopathy as determined by physical examination.
Model for End-Stage Liver Disease (MELD) scores ranging 17-30, (MELD(i) = 0.957 × ln(Cr) + 0.378 × ln(bilirubin) + 1.120 × ln(INR) + 0.643);
Chronic liver disease with definitive etiology such as viral hepatitis, alcohol liver disease, drug induced liver injury or autoimmune liver diseases
Body weight ≥50kg

Exclusion Criteria:

Serious complications in the previous 2 months (e.g., gastrointestinal bleeding: hemoglobin below 90g/L, serious infection such as sepsis, ascites ultrafiltration, and/or dialysis);
Malignant jaundice induced by obstructive jaundice or hemolytic jaundice;
Hepatocellular carcinoma (HCC) diagnosed by radiologic imaging and/or alpha fetoprotein (AFP);
Tumor diagnosed by ultrasound, CT, MR examination;
Moderate or severe chronic heart failure (NYHA III-IV), renal replacement therapy, severe chronic pulmonary disease (GOLD III-IV)
Extrahepatic cholestasis
Hepatic, portal and splenic vein thrombosis diagnosed by doppler ultrasound
Artificial liver support
Previous liver transplantation
Drug abuse in the past 5 years;
Mental disorders and/or has a family history of mental disorder.
HIV infection
Pregnant or breast-feeding females
Highly allergic
Patients can not cooperate or mobility
Enrolled in other clinical trials with 3 months
Patients who can not provide prior informed consent or refusal to participate

Sites / Locations

Tianjin Weikai Bioeng., Ltd.

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Standard Medical Treatment

Mesenchymal Stem Cell

Arm Description

Standard Medical Treatment (SMT): All patients received SMT, including nutritional supplementation; administration of human serum albumin (serum albumin <30 g/L), fresh frozen plasma (200-400 mL/day until the INR was <1.5), S-adenosylmethionine (1.0 g/day); or anti-virus treatment for hepatic viruses-related cases, and appropriate treatment for complications such as infections (including of the respiratory tract, urinary tract, biliary tract, and digestive tract and spontaneous peritonitis), encephalopathy, gastrointestinal bleeding, and hepatorenal syndrome [HRS]).

Mesenchymal Stem Cell (MSC): The MSC group received infusions of 1.0 to 10x10^5cells/kg MSCs through the peripheral vein once a week for 4 weeks, in addition to SMT.

Outcomes

Primary Outcome Measures

survival rate

Number of participants alive

Secondary Outcome Measures

Adverse reactions

Number of participants with adverse reactions (e.g. fever, rash, and diarrhea )

White blood cell

Change of white blood cell count

Platelet

Change of platelet count

Hemoglobin

Change of hemoglobin level

Creatinine

Change of creatinine level as a surrogate marker of liver function

ALT

Change of alanine aminotransferase (ALT) level as a marker of liver function

ALB

Change of albumin (ALB) level as a maker of liver function

TBil

Change of total Bilirubin (TBil) level as a marker of liver function

INRs

Change of international normalized ratio (INRs) level as a marker of liver function

AFP

Change of alpha fetoprotein (AFP) level as a marker of liver function

MELD scores

Model for End-Stage Liver Disease (MELD) score for assessing the severity of chronic liver disease is measured as absolute change to baseline score

Tumor formation

Number of participants with hepatocellular carcinoma or extrahepatic malignant tumors

Liver failure-associated serious complications

Number of participants with liver failure-associated serious complications, such as infections, encephalopathy, gastrointestinal bleeding and HRS

Full Information

NCT ID

NCT03863002

First Posted

February 18, 2019

Last Updated

March 18, 2019

Sponsor

Tianjin Weikai Bioeng., Ltd.

Collaborators

Tianjin Nankai Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03863002

Brief Title

Safety and Efficacy of Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure

Official Title

Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure

Study Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Unknown status

Study Start Date

October 1, 2019 (Anticipated)

Primary Completion Date

October 1, 2021 (Anticipated)

Study Completion Date

October 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tianjin Weikai Bioeng., Ltd.

Collaborators

Tianjin Nankai Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Safety and Efficacy of Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure

Detailed Description

Acute-on-chronic liver failure (ACLF) which occurs in patients with chronic liver disease, is a serious live-threatening disease. Currently, the clinical management, such as liver protection, anti-virus medicine, and artificial liver support, has not significantly improve the outcomes, the mortality still remains over 50%. Liver transplantation is the only effective treatment of ACLF, but this therapy is limited by the shortage of donor organs, potential surgical complications, immunological rejection and high medical costs. Mesenchymal stem cell (MSC) is one of adult stem cells, which has been suggested to play a role in amelioration of liver disease, such as: trans-differentiation of MSCs into hepatocytes, immunomodulation, inhibition of fibrosis development, protective effects on hepatic cell and restoration of hepatic cell proliferation capacity.

6. Conditions and Keywords

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

Liver Failure, Acute on Chronic

Keywords

mesenchymal stem cell

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Masking Description

both participants and the study team are unblinded to the treatment allocation

Allocation

Randomized

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Standard Medical Treatment

Arm Type

No Intervention

Arm Description

Arm Title

Mesenchymal Stem Cell

Arm Type

Experimental

Arm Description

Mesenchymal Stem Cell (MSC): The MSC group received infusions of 1.0 to 10x10^5cells/kg MSCs through the peripheral vein once a week for 4 weeks, in addition to SMT.

Intervention Type

Biological

Intervention Name(s)

Mesenchymal Stem Cell

Intervention Description

Mesenchymal stem cell transplantation via peripheral vein: 1.0-10x10^5 MSCs/kg body weight administered via peripheral vein at week 0, 1, 2, 3 weeks

Primary Outcome Measure Information:

Title

survival rate

Description

Number of participants alive

Time Frame

72 weeks after treatment

Secondary Outcome Measure Information:

Title

Adverse reactions

Description

Number of participants with adverse reactions (e.g. fever, rash, and diarrhea )

Time Frame