Allogenic Bone Marrow Mesenchymal Stem Cell Therapy in Acute-on-chronic Liver Failure (Liveradvance)

February 27, 2024 updated by: Pere Gines

Therapeutic Effects of Allogenic Mesenchymal Stem Cells in Cirrhotic Patients With Acute-on-chronic Liver Failure. A Double-blind Randomized Placebo-controlled Trial

Double-blind placebo randomized controlled trial evaluating the clinical efficacy of allogenic bone marrow derived mesenchymal stem cells in cirrhotic patients with acute-on-chronic liver failure

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Introduction: The most important cause of death in patients with cirrhosis is the development of Acute-on-Chronic Liver Failure (ACLF), a syndrome recently redefined with high mortality. The only effective treatment for ACLF is liver transplantation. However, available organs are limited. Other treatments, such as artificial liver support systems, do not improve survival. ACLF is characterized by increased systemic inflammatory state together with impaired liver regeneration what leads to multiorgan failure. Mesenchymal stem cell (MSC) therapy is an attractive strategy for ACLF owing to the immunomodulatory and regenerative properties of these cells. Aim: To investigate the effects of allogeneic bone marrow MSCs transplantation on liver and other organ functions and systemic inflammation in patients with ACLF. Altruist bone marrow donors will be the source of MSCs. Design and methodology: randomized, double-blind phase I placebo-controlled trial aimed at comparing placebo (solution without cells) and MSCs (4 doses of 2 x 106/kg administered on days 1, 4, 11 and 18). Thirty patients, 15 per group will be included. ACLF will be defined by the CLIF SOFA score and patients stratified according to severity. Outcomes evaluated will be: 1) Organ function (CLIF SOFA and CLIF-C ACLF score); 2) Liver (Child-Pugh and MELD scores,serum bile acids, ammonia and lactate levels), circulatory (systemic and splanchnic hemodynamics, renin, noradrenalin) and endothelial function (nitric oxide, von Willebrand factor); 3 Inflammatory response (serum cytokine panel and transcriptomic analysis of monocytes and polymorphonuclear cells from peripheral blood); 4) Survival at 28 days, 3 and 12 months; and 5) Safety. Expected results: Therapy with MSCs could have beneficial effects on the evolution of patients with ACLF (modulation of inflammatory response and improvement of liver and extra-hepatic organ function) what could translate into an improvement on short-term survival.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
23

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Pere Ginès, MD, PhD
  • Phone Number: 383249 0034 2275400
  • Email: Pgines@clinic.cat

Study Contact Backup

  • Name: Javier Fernandez, MD, PhD
  • Phone Number: 3329 0034 2275400
  • Email: Jfdez@clinic.cat

Study Locations

  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Liver cirrhosis
  • ACLF grade 1, 2 or 3 (Canonic criteria)
  • Signed informed consent

Exclusion Criteria:

  • Acute or subacute liver failure without cirrhosis
  • ACLF grade 1 with response to medical therapy
  • Evidence of current malignancy including hepatocellular carcinoma (any grade) or alphafetoprotein > 400 ng/ml
  • Previous personal history of malignancy (active or in complete remission) or familiar history of hereditary cancer.
  • Moderate or severe chronic heart failure (NYHA III-IV)
  • Renal replacement therapy
  • Severe chronic pulmonary disease (GOLD III-IV)
  • Gastrointestinal bleeding in the last 5 days
  • Previous liver transplantation
  • Immunosuppressive therapy
  • Extrahepatic cholestasis
  • HIV infection
  • Pregnant of breastfeeding women
  • Pre-menopausal women who are of child bearing potential and are not practicing an acceptable method of birth control.
  • Participation in any investigational trial in the last 3 months
  • Active addition to illegal drugs
  • Refusal to participate
  • Patients who can not provide prior informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Allogenic Mesenchymal stem cells
Intravenous allogenic bone marrow derived mesenchymal stem cells: 4 doses of 2 x 106/kg administered on days 1, 4, 11 and 18
Biological: Allogenic mesenchymal stem cells
Cell therapy
Placebo Comparator: Placebo
Solution without cells on days 1, 4, 11 and 18
Other: Placebo
Serum without stem cells

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Change in organ function: chronic liver failure-sequential organ failure assessment (CLIF-SOFA)
Time Frame: Change from Baseline CLIF-SOFA score at 28 days
Change from Baseline CLIF-SOFA score at 28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Child-Pugh score as a marker of liver function
Time Frame: Change from Baseline Child-Pugh score at 28 days, 90 days, one year and 2 years
Child-Pugh
Change from Baseline Child-Pugh score at 28 days, 90 days, one year and 2 years
Model for End-stage Liver Disease (MELD) score as a marker of liver function
Time Frame: Change from Baseline MELD score at 28 days, 90 days, one year and 2 years
MELD scores
Change from Baseline MELD score at 28 days, 90 days, one year and 2 years
serum bile acids as a surrogate marker of liver function
Time Frame: Change from Baseline serum bile acids at 28 days
serum bile acids
Change from Baseline serum bile acids at 28 days
ammonia levels as a surrogate marker of liver function
Time Frame: Change from Baseline serum ammonia at 7, 21 and 28 days
ammonia
Change from Baseline serum ammonia at 7, 21 and 28 days
Lactate levels as a surrogate marker of liver function
Time Frame: Change from Baseline serum lactate levels at 7, 21 and 28 days
lactate levels
Change from Baseline serum lactate levels at 7, 21 and 28 days
Hepatic portal venous gradient (HPVG)
Time Frame: Change from Baseline HPVG at 21 days
HPVG in mmHg
Change from Baseline HPVG at 21 days
Endothelial function measured by nitric oxide levels
Time Frame: Change from Baseline serum nitric oxide levels at 7, 21 and 28 days
Nitric oxide
Change from Baseline serum nitric oxide levels at 7, 21 and 28 days
Endothelial function measured by von Willebrand factor levels
Time Frame: Change from Baseline serum von Willebrand factor levels at 7, 21 and 28 days
von Willebrand factor
Change from Baseline serum von Willebrand factor levels at 7, 21 and 28 days
Renal function measured by serum creatinine
Time Frame: Change from Baseline serum creatinine at 7, 21 and 28 days
serum creatinine
Change from Baseline serum creatinine at 7, 21 and 28 days
Renal function measured by Blood urea nitrogen (BUN)
Time Frame: Change from Baseline serum BUN at 7, 21 and 28 days
serum BUN
Change from Baseline serum BUN at 7, 21 and 28 days
urine neutrophil gelatinase-associated lipocalin (NGAL) as a surrogate marker of renal function
Time Frame: Change from Baseline NGAL at 7, 21 and 28 days
urine neutrophil gelatinase-associated lipocalin (NGAL)
Change from Baseline NGAL at 7, 21 and 28 days
Inflammatory response
Time Frame: Change from Baseline cytokine panel at 4, 11 and 18 days
Serum cytokine panel
Change from Baseline cytokine panel at 4, 11 and 18 days
Transcriptome analysis
Time Frame: Change from Baseline transcriptome analysis at 7-8 days and 12-18 days
Transcriptome analysis of monocytes and polymorphonuclear cells from peripheral blood
Change from Baseline transcriptome analysis at 7-8 days and 12-18 days
Number of participants alive
Time Frame: Number of participants alive at 28 days, 3 months, 12 months and 2 years
Number of participants alive at 28 days, 3 months, 12 months and 2 years
Number of participants with treatment-related adverse events as assessed by World Health Organization (WHO) classification for acute and subacute toxicity
Time Frame: Number of participants with treatment-related adverse events as assessed by WHO classification for acute and subacute toxicity at 2 years
Number of participants with treatment-related adverse events as assessed by WHO classification for acute and subacute toxicity at 2 years
Change in chronic liver failure C acute on chronic liver failure score (clif C ACLF)
Time Frame: Change from Baseline clif C ACLF score at 28 days
Change from Baseline clif C ACLF score at 28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pere Gines

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Clinica Universidad de Navarra, Universidad de Navarra

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Javier Fernandez, MD, PhD, Hospital Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 8, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 5, 2016

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 28, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 27, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2012-003900-11

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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