Safety and Efficacy of SHED for Decompensated Liver Cirrhosis

Safety and Efficacy of Stem Cells From Human Exfoliated Deciduous Teeth for Treatment of Decompensated Liver Cirrhosis

This study is an prospective, randomized control study. Patients with decompensated cirrhosis will be randomly assigned to receive 4 times of SHED treatment plus standard medical care(treatment）or standard medical care (control). The primary outcome is MELD-Na score. Secondary outcomes are Child-Pugh, liver function, life quality and survival.

Study Overview

• Status: Unknown
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Biological: SHED group

Detailed Description

At present, there is still no effective treatment for liver cirrhosis, and the use of stem cells for the treatment of cirrhosis has caused great concern.Stem cells from human exfoliated deciduous teeth (SHED) has been shown to be safe and effective for liver diseases. Randomization controlled studies are needed to confirm the long term effect of SHED treatment for liver cirrhosis. The present study aimed to investigate the safety and efficacy of SHED in hepatitis B related liver cirrhosis patients.

This study is an prospective, randomized control study. Patients with decompensated cirrhosis will be randomly assigned to receive 4 times of SHED treatment plus standard medical care(treatment）or standard medical care (control). SHED infusion (1x10E6 cells/kg body weight) via peripheral vein will be given at week 0,4,8,12.The primary outcome is MELD-Na score. Secondary outcomes are Child-Pugh, liver function, life quality and survival.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Lei Xin, Dr.; Phone Number: 862131161365; Email: aip_xin@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Changhai Hospital
      • Contact: Lei Xin, Dr.; Phone Number: 862131161365; Email: aip_xin@163.com
      • Principal Investigator: Jianya Xue, Dr.
      • Principal Investigator: Lei Xin, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 18-70 years
2. HBV-related liver cirrhosis with presentations of decompensation
3. Antiviral treatment with nucleotide drugs for more than half a year and HBV DNA is less than the minimum detection limit;
4. Child-Pugh score B and MELD-Na score≤25
5. Written consent

Exclusion Criteria:

1. Hepatic encephalopathy, hepatorenal syndrome, acute phase of severe hepatitis
2. Child-Pugh score A or C
3. Hepatocellular carcinoma or other malignancies
4. Cirrhosis or liver failure caused by non-Hepatitis B
5. Pregnancy or breastfeeding
6. Severe bacteria infection,coinfection with HIV or other viral hepatitis.
7. History of severe allergy to biological products or history of immunization within half a year
8. Patients or family members refused to participate in the study
9. Drug abuse or alcohol abuse
10. Other candidates who are judged to be not applicable to this study by doctors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SHED group; SHED transplantation via peripheral vein: 1x10E6 SHEDs/kg body weight administered via peripheral vein at week 0,4,8,12.	Biological: SHED group; 1x10E6 MSCs/kg body weight will be administered via peripheral vein for 4 times at week 0,4,8,12
NO_INTERVENTION: Control; Standard medication for viral hepatitis and cirrhosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Model for End-Stage Liver Disease (MELD)-Na score	The MELD-Na score is a reliable measure of mortality risk in patients with end-stage liver disease. MELD-Na score=3.8ln[bilirubin (mg/dl)]+11.21ln(INR) +9.6ln[creatinine (mg/dl) +6.4* (cause: cholestasis and alcoholic cirrhosis are 0, others are 1) +1.59* (135-Na)	baseline and 4,8,12,16,24 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Child-Pugh score	The Child-Pugh score is a scoring system to measure the severity of chronic liver disease inclusive of cirrhosis. The point scores are added up and classified as: class A: 5-6 points class B: 7-9 points class C: 10-15 points The score is composed from several categories: total bilirubin, μmol/l (mg/dl)<34: 1 point 34-50: 2 points >50: 3 points serum albumin, g/l>35: 1 point 28-35: 2 points <28: 3 points INR<1.7: 1 point 1.7-2.3: 2 points >2.3: 3 points presence of ascites none: 1 point mild: 2 points moderate to severe: 3 points presence of hepatic encephalopathy none: 1 point grades I-II : 2 point grades III-IV: 3 point	baseline and 4,8,12,16,24 week
Changes of liver function	Changes of liver function index such as ALT, AST, ALB, TBIL, PT	baseline and 4,8,12,16,24 week
Changes of life quality	Changes of life quality as assessed by SF-36	baseline and 4,8,12,16,24 week
Survival Rate at half of one year	Survival rate at half of one year	half of one year

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Collaborators: Eastern Hepatobiliary Surgery Hospital; CAR-T (Shanghai) Biotechnology Co., Ltd.
• Investigators: Study Chair: Zhaoshen Li, Dr., Changhai Hospital; Study Director: Chengzhong Li, Dr., Changhai Hospital; Principal Investigator: Lei Xin, Dr., Changhai Hospital; Principal Investigator: Jianya Xue, Dr., Changhai Hospital

Publications and helpful links

General Publications

• Wang D, Zhang H, Liang J, Wang H, Hua B, Feng X, Gilkeson GS, Farge D, Shi S, Sun L. A Long-Term Follow-Up Study of Allogeneic Mesenchymal Stem/Stromal Cell Transplantation in Patients with Drug-Resistant Systemic Lupus Erythematosus. Stem Cell Reports. 2018 Mar 13;10(3):933-941. doi: 10.1016/j.stemcr.2018.01.029. Epub 2018 Mar 1.
• Xuan K, Li B, Guo H, Sun W, Kou X, He X, Zhang Y, Sun J, Liu A, Liao L, Liu S, Liu W, Hu C, Shi S, Jin Y. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci Transl Med. 2018 Aug 22;10(455):eaaf3227. doi: 10.1126/scitranslmed.aaf3227.
• Ohkoshi S, Hara H, Hirono H, Watanabe K, Hasegawa K. Regenerative medicine using dental pulp stem cells for liver diseases. World J Gastrointest Pharmacol Ther. 2017 Feb 6;8(1):1-6. doi: 10.4292/wjgpt.v8.i1.1.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 2, 2019
• Primary Completion (ANTICIPATED): December 31, 2020
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: May 19, 2019
• First Submitted That Met QC Criteria: May 19, 2019
• First Posted (ACTUAL): May 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 3, 2019
• Last Update Submitted That Met QC Criteria: December 1, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Liver Cirrhosis; stem cell; therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: SHED01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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