Acute on Chronic Hepatic FailurePhase 1LiveradvanceNCT02857010
Allogenic Bone Marrow Mesenchymal Stem Cell Therapy in Acute-on-chronic Liver Failure
A Phase 1 study testing Allogenic mesenchymal stem cells in people with Acute on Chronic Hepatic Failure, run by Pere Gines at 1 site in Spain.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Acute on Chronic Hepatic Failure
- What is being tested?
- Allogenic mesenchymal stem cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteSpain
- Study dates
- Feb 2016to Feb 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Liver cirrhosis
- ACLF grade 1, 2 or 3 (Canonic criteria)
- Signed informed consent
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Read the 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.
- Conditions
- Acute on Chronic Hepatic Failure
- Being tested
- Allogenic mesenchymal stem cells, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogenic mesenchymal stem cellsBiological
Cell therapy
PlaceboOther
Serum without stem cells
| Study group | Role | What they receive |
|---|---|---|
| Allogenic Mesenchymal stem cells | Experimental | Intravenous allogenic bone marrow derived mesenchymal stem cells: 4 doses of 2 x 106/kg administered on days 1, 4, 11 and 18 Receives: Biological: Allogenic mesenchymal stem cells |
| Placebo | Placebo comparator | Solution without cells on days 1, 4, 11 and 18 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in organ function: chronic liver failure-sequential organ failure assessment (CLIF-SOFA)
Measured: Change from Baseline CLIF-SOFA score at 28 days
Secondary outcomes (16)
Child-Pugh score as a marker of liver function
Child-Pugh
Measured: 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
MELD scores
Measured: 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
serum bile acids
Measured: Change from Baseline serum bile acids at 28 days
ammonia levels as a surrogate marker of liver function
ammonia
Measured: Change from Baseline serum ammonia at 7, 21 and 28 days
Lactate levels as a surrogate marker of liver function
lactate levels
Measured: Change from Baseline serum lactate levels at 7, 21 and 28 days
Hepatic portal venous gradient (HPVG)
HPVG in mmHg
Measured: Change from Baseline HPVG at 21 days
Endothelial function measured by nitric oxide levels
Nitric oxide
Measured: Change from Baseline serum nitric oxide levels at 7, 21 and 28 days
Endothelial function measured by von Willebrand factor levels
von Willebrand factor
Measured: Change from Baseline serum von Willebrand factor levels at 7, 21 and 28 days
Renal function measured by serum creatinine
serum creatinine
Measured: Change from Baseline serum creatinine at 7, 21 and 28 days
Renal function measured by Blood urea nitrogen (BUN)
serum BUN
Measured: Change from Baseline serum BUN at 7, 21 and 28 days
urine neutrophil gelatinase-associated lipocalin (NGAL) as a surrogate marker of renal function
urine neutrophil gelatinase-associated lipocalin (NGAL)
Measured: Change from Baseline NGAL at 7, 21 and 28 days
Inflammatory response
Serum cytokine panel
Measured: Change from Baseline cytokine panel at 4, 11 and 18 days
Transcriptome analysis
Transcriptome analysis of monocytes and polymorphonuclear cells from peripheral blood
Measured: Change from Baseline transcriptome analysis at 7-8 days and 12-18 days
Number of participants alive
Measured: 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
Measured: 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)
Measured: Change from Baseline clif C ACLF score at 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2016 (estimated)
- Study startFeb 2016
- Primary completionFeb 2018
- Study completionFeb 2020
Why it stopped: Dificulties to recruit patients and dificulties to obtain MSCs.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute on Chronic Hepatic FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pere Gines
- Sponsor type
- University, hospital or other
- Collaborators
- Clinica Universidad de Navarra, Universidad de Navarra
- Responsible party
- Sponsor-investigator, Pere Gines, Hospital Clinic of Barcelona
- Investigators
- Javier Fernandez, MD, PhD, Study chair, Hospital Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02857010
- Sponsor's protocol ID
- 2012-003900-11
- Acronym
- Liveradvance
- Status last verified
- Feb 2024
- First submitted
- 8 Mar 2016
- Last updated
- 28 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Effects of Allogenic Mesenchymal Stem Cells in Cirrhotic Patients With Acute-on-chronic Liver Failure. A Double-blind Randomized Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT02857010
- Acronym / sponsor ID
- Liveradvance / 2012-003900-11
- Conditions
- Acute on Chronic Hepatic Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Dificulties to recruit patients and dificulties to obtain MSCs.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Pere GinesUniversity, hospital or other
- Collaborators
- Clinica Universidad de Navarra, Universidad de Navarra
- Study start
- Feb 2016 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Feb 2020 (actual)
- First posted
- 5 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Allogenic Mesenchymal stem cells | Experimental | Biological: Allogenic mesenchymal stem cellsIntravenous allogenic bone marrow derived mesenchymal stem cells: 4 doses of 2 x 106/kg administered on days 1, 4, 11 and 18 |
| Placebo | Placebo comparator | Other: PlaceboSolution without cells on days 1, 4, 11 and 18 |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Liver cirrhosis
- ACLF grade 1, 2 or 3 (Canonic criteria)
- Signed informed consent
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogenic mesenchymal stem cellsCell therapy | Biological | Allogenic Mesenchymal stem cells |
| PlaceboSerum without stem cells | Other | Placebo |
Primary outcome
Change in organ function: chronic liver failure-sequential organ failure assessment (CLIF-SOFA)
Time frame: Change from Baseline CLIF-SOFA score at 28 days
16 secondary outcomes
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
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
serum bile acids as a surrogate marker of liver function
Time frame: 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
Lactate levels as a surrogate marker of liver function
Time frame: 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
Endothelial function measured by nitric oxide levels
Time frame: 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
Renal function measured by serum creatinine
Time frame: 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
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
Inflammatory response
Time frame: 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
Number of participants alive
Time frame: 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
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
Results and safety
The study was stopped early (reason given: Dificulties to recruit patients and dificulties to obtain MSCs.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Javier Fernandez, MD, PhD study chair
Hospital Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Allogenic mesenchymal stem cells in people with Acute on Chronic Hepatic Failure, run by Pere Gines at 1 site in Spain.
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 18 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: stopped early, as of the sponsor's last update on 28 Feb 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 Spain. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Dificulties to recruit patients and dificulties to obtain MSCs.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in organ function: chronic liver failure-sequential organ failure assessment (CLIF-SOFA) (time frame: Change from Baseline CLIF-SOFA score at 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Feb 2024.