Human Umbilical Cord Mesenchymal Stem Cell Transplantation for The Treatment of Acute-on-Chronic Liver Failure

NCT05985863 | Recruiting Phase 1

• 1 other identifier: 2022YFC2304402
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized double-blind placebo-controlled multicenter clinical trial to evaluate the safety and efficacy of human umbilical cord mesenchymal stem cell (UC-MSC) transplantation for the treatment of acute-on-chronic liver failure (ACLF). UC-MSC therapy may improve the clinical outcomes of patients with ACLF. The trial would provide scientific evidence for UC-MSC transplantation as a potential treatment for ACLF.

Conditions

Acute-On-Chronic Liver Failure

Keywords

Mesenchymal Stem Cells; Acute-On-Chronic Liver Failure; Therapeutics

Outcome Measures

Primary Outcomes (2)

• Transplantation free survival rate

  Transplantation free survival rate of ACLF patients.

  week1, week2, week3, week4, week5, week8, week12, week24, week53

• Incidence of Treatment-Emergent Adverse Events

  Safety and Tolerability of UC-MSCs transplantation.

  day0, day3, week1, week2, week3, week4, week5, week8, week12, week24, week53

Secondary Outcomes (6)

• International Normalized Ratio (INR)

  week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53

• Concentration of Total Bilirubin (TBIL, mg/dL)

  week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53

• Concentration of Serum Albumin (ALB, g/L)

  week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53

• Concentration of Blood Urea Nitrogen (BUN, mmol/L)

  week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53

• The Model for End-Stage Liver Disease(MELD) score

  week-1, week1, week2, week4, week5, week12, week24, week53

Study Arms (3)

Group Control

PLACEBO COMPARATOR

standard medical treatment+Placebo(5% human serum albumin in 0.9% saline, at week0, week1 and week2)

Drug: standard medical treatment; Drug: Placebo

Group MSC-1

EXPERIMENTAL

Patients received standard medical treatment and infusions of hUC-MSC(1.5×10\^8) via peripheral veins once a week for 3 timess(at week0, week1, and week2).

Drug: standard medical treatment; Drug: hUC-MSC

Group MSC-2

EXPERIMENTAL

Patients in Group MSC-1 received standard medical treatment and infusions of hUC-MSC(1.5×10\^8) via peripheral veins once a week for another 2 timess(at week4 and week5).

Drug: standard medical treatment; Drug: hUC-MSC; Drug: hUC-MSC_Prolonged

Interventions

standard medical treatment DRUG

standard medical treatment for ACLF

Group Control; Group MSC-1; Group MSC-2

Placebo DRUG

5% human serum albumin in 0.9% saline (at week0, week1 and week2)

Group Control

hUC-MSC DRUG

hUC-MSC (1.5×10\^8 cells/time, Peripheral IV, at week0, week1 and week2)

Group MSC-1; Group MSC-2

hUC-MSC_Prolonged DRUG

hUC-MSC (1.5×10\^8 cells/time, Peripheral IV, at week4 and week5)

Group MSC-2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old ≤ age ≤ 70 years old, gender is not limited.
• Meet the APASL definition of ACLF: acute liver injury in patients with previously diagnosed or undiagnosed chronic liver disease or cirrhosis, manifested as jaundice (total bilirubin levels of 5 mg/dl or more) and coagulopathy (INR of 1.5 or more, or prothrombin activity of less than 40%） complicated within 4 weeks by clinical ascites, encephalopathy, or both.
• Willing to sign the informed consent form.

You may not qualify if:

• Patients with acute kidney injury, upper gastrointestinal hemorrhage, hepatic encephalopathy above grade II (inclusive) or uncontrolled infection at baseline;
• Before the onset of liver failure, the previous indicators of the patient included PLT\<50×10\^9/L or Child-Pugh score\>9;
• Combined with liver cancer or other malignant tumors;
• Patients with previous liver transplantation or planned liver transplantation within 3 months;
• Severe organic disease of primary extrahepatic organs;
• Those who have a history of venous thrombosis or pulmonary embolism are judged by the investigator to be ineligible to participate in this trial;
• Pregnant, breastfeeding women or those who plan to have a baby in the near future;
• Those who are highly allergic or have a history of severe allergies;
• Those who have received immunosuppressant and immune enhancer treatment within 1 month;
• Drug abuse in the past 5 years;
• Alcohol withdrawal symptoms;
• A history of severe mental disorders within 24 months before screening, including uncontrolled major depression or controlled or uncontrolled psychosis;
• Those who have participated or are participating in other clinical trials within three months before screening, or have previously received stem cell therapy;
• Other conditions that the investigator thinks that the patient is not suitable to participate in this study.

Sponsors & Collaborators

• Beijing 302 Hospital: lead
• Shulan (Hang Zhou) Hospital: collaborator
• BeijingYouan Hospital: collaborator
• Shenzhen Third People's Hospital: collaborator
• Shen Zhen Wingor Biotechnology CO. LTD: collaborator

Study Sites (1)

the Fifth Medical Center, Chinese PLA General Hospital

Beijing, Beijing Municipality, 100039, China

RECRUITING

Related Publications (11)

• Lin BL, Chen JF, Qiu WH, Wang KW, Xie DY, Chen XY, Liu QL, Peng L, Li JG, Mei YY, Weng WZ, Peng YW, Cao HJ, Xie JQ, Xie SB, Xiang AP, Gao ZL. Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial. Hepatology. 2017 Jul;66(1):209-219. doi: 10.1002/hep.29189. Epub 2017 May 27.

  PMID: 28370357 BACKGROUND

• Schacher FC, Martins Pezzi da Silva A, Silla LMDR, Alvares-da-Silva MR. Bone Marrow Mesenchymal Stem Cells in Acute-on-Chronic Liver Failure Grades 2 and 3: A Phase I-II Randomized Clinical Trial. Can J Gastroenterol Hepatol. 2021 Aug 4;2021:3662776. doi: 10.1155/2021/3662776. eCollection 2021.

  PMID: 34395335 BACKGROUND

• Xu WX, He HL, Pan SW, Chen YL, Zhang ML, Zhu S, Gao ZL, Peng L, Li JG. Combination Treatments of Plasma Exchange and Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation for Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure: A Clinical Trial in China. Stem Cells Int. 2019 Feb 4;2019:4130757. doi: 10.1155/2019/4130757. eCollection 2019.

  PMID: 30863450 BACKGROUND

• Shi M, Zhang Z, Xu R, Lin H, Fu J, Zou Z, Zhang A, Shi J, Chen L, Lv S, He W, Geng H, Jin L, Liu Z, Wang FS. Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl Med. 2012 Oct;1(10):725-31. doi: 10.5966/sctm.2012-0034. Epub 2012 Oct 11.

  PMID: 23197664 BACKGROUND

• Li YH, Xu Y, Wu HM, Yang J, Yang LH, Yue-Meng W. Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation in Hepatitis B Virus Related Acute-on-Chronic Liver Failure Treated with Plasma Exchange and Entecavir: a 24-Month Prospective Study. Stem Cell Rev Rep. 2016 Dec;12(6):645-653. doi: 10.1007/s12015-016-9683-3.

  PMID: 27687792 BACKGROUND

• Yu H, Feng Y, Du W, Zhao M, Jia H, Wei Z, Yan S, Han Z, Zhang L, Li Z, Han Z. Off-the-shelf GMP-grade UC-MSCs as therapeutic drugs for the amelioration of CCl4-induced acute-on-chronic liver failure in NOD-SCID mice. Int Immunopharmacol. 2022 Dec;113(Pt A):109408. doi: 10.1016/j.intimp.2022.109408. Epub 2022 Nov 9.

  PMID: 36461584 BACKGROUND

• Gilsanz C, Aller MA, Fuentes-Julian S, Prieto I, Blazquez-Martinez A, Argudo S, Fernandez-Delgado J, Belena J, Arias J, De Miguel MP. Adipose-derived mesenchymal stem cells slow disease progression of acute-on-chronic liver failure. Biomed Pharmacother. 2017 Jul;91:776-787. doi: 10.1016/j.biopha.2017.04.117. Epub 2017 May 10.

  PMID: 28501004 BACKGROUND

• Maheshwari D, Kumar D, Jagdish RK, Nautiyal N, Hidam A, Kumari R, Sehgal R, Trehanpati N, Baweja S, Kumar G, Sinha S, Bajpai M, Pamecha V, Bihari C, Maiwall R, Sarin SK, Kumar A. Bioenergetic Failure Drives Functional Exhaustion of Monocytes in Acute-on-Chronic Liver Failure. Front Immunol. 2022 Jun 3;13:856587. doi: 10.3389/fimmu.2022.856587. eCollection 2022.

  PMID: 35747140 BACKGROUND

• He Y, Guo X, Lan T, Xia J, Wang J, Li B, Peng C, Chen Y, Hu X, Meng Z. Human umbilical cord-derived mesenchymal stem cells improve the function of liver in rats with acute-on-chronic liver failure via downregulating Notch and Stat1/Stat3 signaling. Stem Cell Res Ther. 2021 Jul 13;12(1):396. doi: 10.1186/s13287-021-02468-6.

  PMID: 34256837 BACKGROUND

• Lin D, Chen H, Xiong J, Zhang J, Hu Z, Gao J, Gao B, Zhang S, Chen J, Cao H, Li Z, Lin B, Gao Z. Mesenchymal stem cells exosomal let-7a-5p improve autophagic flux and alleviate liver injury in acute-on-chronic liver failure by promoting nuclear expression of TFEB. Cell Death Dis. 2022 Oct 12;13(10):865. doi: 10.1038/s41419-022-05303-9.

  PMID: 36224178 BACKGROUND

• Wang Y, Li M, Yang T, Xie Y, Wang FS, Hu J, Shi M. Human umbilical cord mesenchymal stem cell transplantation for the treatment of acute-on-chronic liver failure: protocol for a multicentre random double-blind placebo-controlled trial. BMJ Open. 2024 Jun 25;14(6):e084237. doi: 10.1136/bmjopen-2024-084237.

  PMID: 38925694 DERIVED

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Ming Shi, PhD

  the Fifth Medical Center, Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tao Yang, MD

CONTACT

86-010-66933333; y_t_0321@163.com

Yanhu Wang, MM

CONTACT

86-010-66933328; 2440477984@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 14, 2023
• Study Start: September 30, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)