Safety and Efficacy of SHED for Decompensated Liver Cirrhosis

Liver Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03957655
• Other study ID #: SHED01
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: December 2, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: December 2019
• Source: Changhai Hospital
• Contact: Lei Xin, Dr.
• Phone: 862131161365
• Email: aip_xin[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis

Intervention

Biological:
• SHED group
1x10E6 MSCs/kg body weight will be administered via peripheral vein for 4 times at week 0,4,8,12

Locations

Country	Name	City	State
China	Changhai Hospital	Shanghai	Shanghai

Sponsors (3)

Lead Sponsor	Collaborator
Changhai Hospital	CAR-T (Shanghai) Biotechnology Co., Ltd., Eastern Hepatobiliary Surgery Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Changes of liver function	Changes of liver function index such as ALT, AST, ALB, TBIL, PT	baseline and 4,8,12,16,24 week
Secondary	Changes of life quality	Changes of life quality as assessed by SF-36	baseline and 4,8,12,16,24 week
Secondary	Survival Rate at half of one year	Survival rate at half of one year	half of one year