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出境医 / 临床实验 / Safety and Efficacy of SHED for Decompensated Liver Cirrhosis

Safety and Efficacy of SHED for Decompensated Liver Cirrhosis

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Liver Cirrhosis Biological: SHED group Early Phase 1

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: Outcome assessors will be blind to the randomization results of the participants.
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Stem Cells From Human Exfoliated Deciduous Teeth for Treatment of Decompensated Liver Cirrhosis
Estimated Study Start Date : December 2, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021
Arms and Interventions
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
Outcome Measures
Primary Outcome Measures :
  1. Model for End-Stage Liver Disease (MELD)-Na score [ Time Frame: baseline and 4,8,12,16,24 week ]

    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)



Secondary Outcome Measures :
  1. Child-Pugh score [ Time Frame: baseline and 4,8,12,16,24 week ]

    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


  2. Changes of liver function [ Time Frame: baseline and 4,8,12,16,24 week ]
    Changes of liver function index such as ALT, AST, ALB, TBIL, PT

  3. Changes of life quality [ Time Frame: baseline and 4,8,12,16,24 week ]
    Changes of life quality as assessed by SF-36

  4. Survival Rate at half of one year [ Time Frame: half of one year ]
    Survival rate at half of one year


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations

Contacts
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Contact: Lei Xin, Dr. 862131161365 aip_xin@163.com

Locations
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China, Shanghai
Changhai Hospital
Shanghai, Shanghai, China, 200433
Contact: Lei Xin, Dr.    862131161365    aip_xin@163.com   
Principal Investigator: Jianya Xue, Dr.         
Principal Investigator: Lei Xin, Dr.         
Sponsors and Collaborators
Changhai Hospital
Eastern Hepatobiliary Surgery Hospital
CAR-T (Shanghai) Biotechnology Co., Ltd.
Investigators
Layout table for investigator information
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
Tracking Information
First Submitted Date  ICMJE May 19, 2019
First Posted Date  ICMJE May 21, 2019
Last Update Posted Date December 3, 2019
Estimated Study Start Date  ICMJE December 2, 2019
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2019) 		Model for End-Stage Liver Disease (MELD)-Na score [ Time Frame: baseline and 4,8,12,16,24 week ]
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)
Original Primary Outcome Measures  ICMJE
 (submitted: May 19, 2019) 		MELD-Na score [ Time Frame: baseline and 4,8,12,16,24 week ]
Changes of liver functions as assessed by MELD-Na score
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2019)
  • Child-Pugh score [ Time Frame: baseline and 4,8,12,16,24 week ]
    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
  • Changes of liver function [ Time Frame: baseline and 4,8,12,16,24 week ]
    Changes of liver function index such as ALT, AST, ALB, TBIL, PT
  • Changes of life quality [ Time Frame: baseline and 4,8,12,16,24 week ]
    Changes of life quality as assessed by SF-36
  • Survival Rate at half of one year [ Time Frame: half of one year ]
    Survival rate at half of one year
Original Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2019)
  • Child-Pugh [ Time Frame: baseline and 4,8,12,16,24 week ]
    Changes of liver functions as assessed by Child-Pugh
  • Changes of liver function [ Time Frame: baseline and 4,8,12,16,24 week ]
    Changes of liver function index such as ALT, AST, ALB, TBIL, PT
  • Changes of life quality [ Time Frame: baseline and 4,8,12,16,24 week ]
    Changes of life quality as assessed by SF-36
  • Survival Rate at half of one year [ Time Frame: half of one year ]
    Survival rate at half of one year
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of SHED for Decompensated Liver Cirrhosis
Official Title  ICMJE Safety and Efficacy of Stem Cells From Human Exfoliated Deciduous Teeth for Treatment of Decompensated Liver Cirrhosis
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
Outcome assessors will be blind to the randomization results of the participants.
Primary Purpose: Treatment
Condition  ICMJE Liver Cirrhosis
Intervention  ICMJE Biological: SHED group
1x10E6 MSCs/kg body weight will be administered via peripheral vein for 4 times at week 0,4,8,12
Study Arms  ICMJE
  • Experimental: SHED group
    SHED transplantation via peripheral vein: 1x10E6 SHEDs/kg body weight administered via peripheral vein at week 0,4,8,12.
    Intervention: Biological: SHED group
  • No Intervention: Control
    Standard medication for viral hepatitis and cirrhosis
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). pii: 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: December 1, 2019) 		40
Original Estimated Enrollment  ICMJE
 (submitted: May 19, 2019) 		60
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lei Xin, Dr. 862131161365 aip_xin@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03957655
Other Study ID Numbers  ICMJE SHED01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Zhaoshen Li, Changhai Hospital
Study Sponsor  ICMJE Changhai Hospital
Collaborators  ICMJE
  • Eastern Hepatobiliary Surgery Hospital
  • CAR-T (Shanghai) Biotechnology Co., Ltd.
Investigators  ICMJE
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
PRS Account Changhai Hospital
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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