Safety and Efficacy Study of Co-transfering of Mesenchymal Stem Cell and Regulatory T Cells in Treating End-stage Liver Disease

Phase 1 Clinical Trial Using Mesenchymal Stem Cell and Regulatory T Cells as Individualized Medicine to Evaluate the Safety and Efficacy in End-stage Liver Disease

Cirrhosis of the liver is a common clinical chronic progressive liver disease, which is a diffuse liver lesion caused by one or more causes over a long period of time or repeatedly. Nodules, abnormal spherical areas of cells, form as dying liver cells are replaced by regenerating cells. This regeneration of cells causes the liver to become hard. The potential for stem cells to differentiate into hepatocytes cells was recently confirmed. In particular, mesenchymal stem cell (MSC) transplantation has been applicated in the clinic for treat several human diseases such as liver injury and liver fibrosis displayed good tolerance and efficiency. Besides, regulatory T cells(Tregs) had been proved as an immune regualtory T cell subsets, which could reduce immune cell activation and reduce liver injury severity. The purpose of this study is to learn whether and how MSCs and Tregs can improve the disease conditions in patients with decompensated cirrhosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Biological: MSC and Tregs

Detailed Description

Cirrhosis of the liver is a common clinical chronic progressive liver disease, which is a diffuse liver lesion caused by one or more causes over a long period of time or repeatedly. Nodules, abnormal spherical areas of cells, form as dying liver cells are replaced by regenerating cells. This regeneration of cells causes the liver to become hard. Decompensated liver cirrhosis is mainly manifested by liver function damage and portal hypertension, with multiple system involvement. Complications such as upper gastrointestinal hemorrhage, hepatic encephalopathy, secondary infection, hypersplenism, ascites, and carcinogenesis often occur in the late stage. The potential for stem cells to differentiate into hepatocytes cells was recently confirmed. In particular, mesenchymal stem cell (MSC) and Tregs transplantation had been applicated in the clinic for treat several human diseases such as liver injury and liver fibrosis displayed good tolerance and efficiency. The purpose of this study is to learn whether and how MSCs and Tregs can improve the disease conditions in patients with decompensated cirrhosis.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Nanjing Medical University
      • Contact: Ling Lu, M.D, PH. D.; Phone Number: 86-025-68136053; Email: lvling@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinically diagnosed as decompensated liver cirrhosis.
2. Hepatitis B/C Liver Cirrhosis After Viral Treatment, HBV/HCV Viral Loads Below Detection Level over six mouths, and the liver function remained below Child-pugh A grade or MELD score >10.
3. Other causes of cirrhosis, liver function compensatory incomplete. In the past year, despite active medical treatment taken, the condition has continued to increase, at least because of cirrhosis complications such as ascites, spontaneous peritonitis, gastrointestinal bleeding, and hepatic encephalopathy in hospital over one time.
4. Need to intermittently supplement albumin and apply diuretic therapy.
5. Albumin <35 g/L, total bilirubin <170 umol/L, prothrombin activity> 30%; (Prothrombin time <20 s, moderate or lower mass ascites, spontaneous peritonitis and hepatic encephalopathy (grade II or lower), Child-pugh score> 5 points).
6. There was no history of gastrointestinal hemorrhage within the last month and population with no high-risk portal hypertension and gastrointestinal bleeding was evaluated recently.
7. Unconditional acceptance of orthotopic liver transplantation.
8. Aged from 18 to 65 years.
9. Voluntarily signed informed consent form.

Exclusion Criteria:

1. A malignant tumor with liver or other organs or a history of previous cancer.
2. Complications include gastrointestinal bleeding, spontaneous peritonitis, hepatic encephalopathy, hepatorenal syndrome, and Acute infection episodes.
3. Patients with severe heart, lung, kidney or blood system diseases and failure status.
4. Pregnant or lactating women.
5. Allergic constitution.
6. There is a history of alcohol abuse, drug abuse, and failure to effectively quit.
7. Patients did not participate in other clinical trials within 4 weeks.
8. Any condition, investigator believe that patients should not participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Conventional plus MSC and Tregs treatment	Biological: MSC and Tregs; conventional plus MSC and Tregs or placebo treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Albumin (ALB)	The evaluation of serum levels of ALB	24 months
Alanine aminotransferase (ALT)	The evaluation of serum levels of ALT	24 months
Prealbumin (PA)	The evaluation of serum levels of PA	24 months
Total bilirubin (TB)	The evaluation of serum levels of TB	24 months
Direct bilirubin (DB)	The evaluation of serum levels of DB	24 months
Blood urea nitrogen (BUN)	The evaluation of serum levels of BUN	24 months
Uric acid (UA)	The evaluation of serum levels of UA	24 months
Serum creatinine (Scr)	The evaluation of serum levels of Scr	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Child-Pugh	The evaluation of Child-Pugh score for liver function	24 months
Model for end-stage liver disease (MELD)	The evaluation of MELD score for severity of liver disease	24 months
Quality of life (QOL)	The evaluation of QOL score for life quality	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of liver fibrosis	The pathology decrease in grade of liver fibrosis	24 months

Collaborators and Investigators

• Sponsor: Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2020
• Primary Completion (ANTICIPATED): March 1, 2025
• Study Completion (ANTICIPATED): September 1, 2025

Study Registration Dates

• First Submitted: February 23, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (ACTUAL): March 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 1, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Fibrosis; Liver Diseases; End Stage Liver Disease; Liver Cirrhosis
• Other Study ID Numbers: NJLT005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No