AzTrials
AzTrials

Acute-On-Chronic Liver FailurePhase 1/2NCT05985863

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

A Phase 1/2 study testing standard medical treatment, hUC-MSC and hUC-MSC_Prolonged in people with Acute-On-Chronic Liver Failure, run by Beijing 302 Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Acute-On-Chronic Liver Failure
What is being tested?
standard medical treatment, hUC-MSC and hUC-MSC_Prolonged
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
150 participants
Where
1 siteChina
Study dates
30 Sep 2023to 30 Dec 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 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.

Who cannot join

  • 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;
Show all 14Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Tao Yang, MD contact

86-010-66933333

y_t_0321@163.com

Yanhu Wang, MM contact

86-010-66933328

2440477984@qq.com

China1 site, 1 recruiting

  • the Fifth Medical Center, Chinese PLA General Hospital

    Beijing, Beijing Municipality, 100039

    Tao Yang, MD, 010-66933333, y_t_0321@163.com

    Mengyao Li, MB, 010-66933333, qianlimengyao@163.com

    Recruiting

Other trials in China

About this study

Official title: Clinical Research of Human Umbilical Cord Mesenchymal Stem Cell Transplantation for The Treatment of Acute-on-Chronic Liver Failure

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.

Read the detailed description

Acute-on-chronic liver failure (ACLF) has been proposed to define a distinct syndrome which is characterized by an intense systemic inflammatory response, single- or multiple organ system failures, and high 28-day mortality. Current treatments for liver failure are still limited, and liver transplantation remains the only available approach to improve survival but is restricted by a shortage of organ resources, rejection after transplantation, and heavy financial costs. In the past decade, a series of new applications based on mesenchymal stem cell (MSC) therapy have been studied as an alternative interventional method for chronic liver diseases. This randomized double-blind placebo-controlled multicenter clinical trial is aimed at determining the safety and clinical efficacy of UC-MSC transfusions in ACLF patients.

A total of 150 ACLF patients would be enrolled,100patients would be assigned to the MSC intervention group and the other 50 patients would be assigned to the placebo control group. This trial is two-stage randomized designed. At the first stage, the patients would be randomized into two groups, the placebo short control group would receive standard medical treatment plus 3 times placebo (at week0, week1 and week2), while the MSC short treatment group would receive standard medical treatment plus 3 times hUC-MSC (1.5×10^8, Peripheral IV, at week0, week1 and week2). The two groups would be followed up for 2 weeks, and unblinding would be conducted at week4. At the second stage, the survived patients of the MSC short treatment group would be further randomized and blinded into another two groups. The MSC Prolonged treatment group would receive another 2 times hUC-MSC (1.5×10^8, Peripheral IV, at week4 and week5), while the MSC Prolonged control group would receive 2 times placebo (at week4 and week5).

Transplantation free survival rate and incidence of treatment-emergent adverse events would be the primary outcomes, and other outcomes such as international normalized ratio (INR), total bilirubin (TBIL, mg/dL), serum albumin (ALB, g/L), blood urea nitrogen (BUN, mmol/l), the model for end-stage liver disease(MELD) score and child-turcotte-pugh(CTP) score would also be measured.

Being tested
standard medical treatment, Placebo, hUC-MSC, hUC-MSC_Prolonged
Keywords
Mesenchymal Stem Cells, Acute-On-Chronic Liver Failure, Therapeutics
Medical subject headings
Acute-On-Chronic Liver Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • standard medical treatmentDrug

    standard medical treatment for ACLF

  • PlaceboDrug

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

  • hUC-MSCDrug

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

  • hUC-MSC_ProlongedDrug

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

Study groups in NCT05985863
Study groupRoleWhat they receive
Group ControlPlacebo comparatorstandard medical treatment+Placebo(5% human serum albumin in 0.9% saline, at week0, week1 and week2)
Receives: Drug: standard medical treatment; Drug: Placebo
Group MSC-1ExperimentalPatients 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).
Receives: Drug: standard medical treatment; Drug: hUC-MSC
Group MSC-2ExperimentalPatients 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).
Receives: Drug: standard medical treatment; Drug: hUC-MSC; Drug: hUC-MSC_Prolonged

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Transplantation free survival rate

    Transplantation free survival rate of ACLF patients.

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

  2. Incidence of Treatment-Emergent Adverse Events

    Safety and Tolerability of UC-MSCs transplantation.

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

Secondary outcomes (6)

  1. International Normalized Ratio (INR)

    INR was introduced as a standardized reporting mechanism allowing comparisons across laboratories and patients. Consensus guidelines recommend that INR ≥ 1.5 can be used as a threshold, and current recommendations for targeting an INR of < 1.5 were based on studies across all surgical disciplines.

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

  2. Concentration of Total Bilirubin (TBIL, mg/dL)

    Total bilirubin refers to the concentration of bilirubin in a patient's blood sample, which is automatically measured by the laboratories in accordance with standard operating procedures. APASL defines ACLF as "an acute hepatic insult manifesting as jaundice (Serum Bilirubin ≥ 5 mg/dL) and coagulopathy (international normalized ratio [INR] ≥ 1.5) complicated within 4 weeks by clinical ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease/cirrhosis, that is associated with a high 28-day mortality."

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

  3. Concentration of Serum Albumin (ALB, g/L)

    Serum albumin refers to the concentration of albumin in a patient's serum, which is automatically measured by the laboratory in accordance with standard operating procedures. Serum albumin is an independent protective factor for 30-day prognosis in ACLF patients.

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

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

    Blood urea nitrogen refers to the concentration of urea nitrogen in a patient's blood sample. Blood urea nitrogen is a commonly used indicator of renal function in clinic.

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

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

    R = 3.8×ln [TBiL (mg/dl)] +11.2×ln (INR) +9.6×ln [Cr (mg/dl)] +6.4× (Cause: biliary or alcoholic is 0, other is 1), the result is taken as an integer. Studies have shown that the optimal critical value of MELD score to judge the short-term prognosis of ACLF patients is 30, and when MELD score is greater than 30, the case fatality rate of patients within 3 months is significantly increased.

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

  6. Child-Turcotte-Pugh(CTP) score

    CTP score is currently the most commonly used model to evaluate liver reserve function and prognosis in patients with cirrhosis. This model evaluates liver function based on HE grade, degree of abdominal fluid accumulation, bilirubin (TBiL), albumin (Alb) and prothrombin time (PT). The score ranges from 0 to 15, with the higher the score, the worse the prognosis.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2023
  2. Study start30 Sep 2023
  3. Primary completion30 Dec 2026 (estimated)
  4. Study completion30 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05985863
Sponsor's protocol ID
2022YFC2304402
Status last verified
May 2024
First submitted
24 Jul 2023
Last updated
7 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 28370357

  • 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.

    PubMed 34395335

  • 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.

    PubMed 30863450

  • 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.

    PubMed 23197664

  • 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.

    PubMed 27687792

  • 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.

    PubMed 36461584

  • 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.

    PubMed 28501004

  • 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.

    PubMed 35747140

  • 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.

    PubMed 34256837

  • 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.

    PubMed 36224178

  • 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.

    PubMed 38925694

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing standard medical treatment, hUC-MSC and hUC-MSC_Prolonged in people with Acute-On-Chronic Liver Failure, run by Beijing 302 Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tao Yang, MD (86-010-66933333, y_t_0321@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Transplantation free survival rate (time frame: week1, week2, week3, week4, week5, week8, week12, week24, week53). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05985863, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in