Liver TransplantationNCT01445236
Pilot Study of Immunosuppression Drug Weaning in Liver Recipients Exhibiting Biomarkers of High Likelihood of Tolerance
A study testing Immunosuppresion withdrawal in people with Liver Transplantation, run by Hospital Clinic of Barcelona at 1 site in Spain.
Trial summary
Immunosuppressive drugs can be successfully withdrawn in a fraction of liver transplant patients. Specific peripheral blood gene expression markers can be employed to select patients with a high likelihood of being tolerant. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- Immunosuppresion withdrawal
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteSpain
- Study dates
- Sep 2011to Jan 2013
- Phase
- Interventional
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Liver transplant recipients with at least 3 years of post-operative follow-up in whom gene expression pattern changed from non-tolerant to tolerant under sirolimus treatment.
- Feasibility of performing very frequent (every 2-3 weeks) clinical follow-up visits.
- No history of graft rejection during the previous 12 months.
- Basal liver biopsy without signs of rejection
- Stability of liver graft function, defined as: a) normal liver function tests (AST, ALT, ALP, GGT) during at least 6 months; or alternatively b) minor alterations in liver function tests that have not changed over the previous 6 months (AST/ALT < 2 fold normal levels; ALP < 1.5 fold normal levels; GGT < 2 fold normal levels; bilirubin < 2 mg/dL).
- Presence of peripheral blood biomarkers of high likelihood of tolerance as defined by: a) transcriptional pattern associated with tolerance regardless of the basal immunosuppressive regimen; and/or b) 2-fold increase in Treg frequency in patients who have discontinued calcineurin inhibitors in the 12 months prior to inclusion.
- Signature of informed consent.
Who cannot join
- Requirement of immunosuppressive treatment for an indication different to liver transplantation.
- Documented human immunodeficiency virus (HIV) infection.
- Liver-Kidney transplant recipients.
- History of liver autoimmune disease (autoimmune hepatitis, primary liver cirrhosis, primary sclerosing cholangitis)
- Active hepatitis C virus infection as defined by positive serum HCV-RNA.
Trial locations and contacts
1 site in 1 country.
About this study
Immunosuppressive drugs can be successfully withdrawn in a fraction of liver transplant patients. Specific peripheral blood gene expression markers can be employed to select patients with a high likelihood of being tolerant. In the current study the investigators propose to conduct a pilot non-randomized prospective study in which gradual weaning of immunosuppressive drugs will be offered to liver recipients exhibiting a favorable peripheral blood gene expression profile.
Read the detailed description
HYPOTHESIS We hypothesize that liver recipients exhibiting either specific gene expression and/or cell phenotypic markers in peripheral blood will be successfully weaned from all immunosuppressive drugs.
OBJECTIVE Evaluate the applicability of a set of non-invasive biomarkers in the identification of liver transplant recipients who can successfully discontinue all immunosuppressive therapy.
METODOLOGY
- Immunosuppression drug weaning: according to the clinical protocol approved, all patients will undergo liver biopsy before entry. Patients will be visited every 4 weeks, and immunosuppressive drugs will be gradually discontinued with the aim of achieving 50% decrease in drug dosages by month 3, and complete withdrawal by month 6 after initiation of the study. Following drug discontinuation, patients will continue to be followed every month until month 12 after initiation of the study. Liver function tests will be obtained at every clinical follow-up visit.
- Management of liver function test alterations: a) Increases in liver function tests below 2-fold normal levels for AST/ALT/GGT or 1.5-fold normal levels for ALP will result in no further decreases in drug dosages, and performance of new liver function tests in 14 days. Worsening or persistence of liver function test alterations will constitute indication for liver biopsy. b) Increases in liver function tests beyond 2-fold normal levels for AST/ALT/GGT or1.5-fold normal levels for ALP.
- Diagnosis of liver graft rejection: will be based on the finding of 2 out of 3 of the following histological criteria: portal inflammation, injury to bile duct epithelium, and endothelitis. The finding of a mixed portal/loblular lymphocytic infiltrate not attributable to any other cause and responding to an increase in immunosuppressive drug doses will also be considered as a rejection.
- Management of rejection episodes: patients presenting with mild to moderate acute rejection will be treated with 20 mg of prednisone in decreasing doses within 4 to 6 weeks. Patients with severe acute rejection will be admitted to hospital and treated with high dose IV prednisone (500-1000mg/day) during 3 day and thereafter oral prednisone at decreasing dose according to evolution of liver function tests. In every case patients will return to previous immunosuppressive dose enough to maintained normal or near normal liver function test.
SAMPLE SIZE According to our data, the success rate of an immunosuppression withdrawal strategy in stable liver transplant recipients transplanted for more than 3 year is 42% (these patients are consider as operationally tolerants). Our hypothesis is that with the use of biomarkers to identify potential tolerant patients the investigators will be able to increase the success rate of this strategy up to 78%. In order to achieve this success rate the sample size needed in this study is 25 patients (power 80% and significance of 95%).
- Conditions
- Liver Transplantation
- Being tested
- Immunosuppresion withdrawal
- Keywords
- Operational tolerance, Biomarkers, Liver Transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunosuppresion withdrawalOther
Also called Cyclosporine A, Tacrolimus
Gradual discontinuation of all immunosuppressive drugs.
| Study group | Role | What they receive |
|---|---|---|
| Weaning patients | Experimental | Not described Receives: Other: Immunosuppresion withdrawal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients developing operational tolerance
Measured: 12 months after complete withdrawal of all immunosuppressive drugs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2011 (estimated)
- Study startSep 2011
- Primary completionJan 2013
- Study completionJan 2013
Why it stopped: Insufficient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- More trials run by Hospital Clinic of BarcelonaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Clinic of Barcelona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alberto Sanchez-Fueyo, Hospital Clinic of Barcelona
- Investigators
- Alberto Sanchez-Fueyo, MD, Principal investigator, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01445236
- Sponsor's protocol ID
- Weaning-Biomarkers
- Status last verified
- Dec 2013
- First submitted
- 29 Sep 2011
- Last updated
- 20 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Immunosuppression Drug Weaning in Liver Recipients Exhibiting Biomarkers of High Likelihood of Tolerance
- ClinicalTrials.gov ID
- NCT01445236
- Acronym / sponsor ID
- Weaning-Biomarkers
- Conditions
- Liver Transplantation
- Keywords
- Operational tolerance, Biomarkers, Liver Transplantation
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient recruitment
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Hospital Clinic of BarcelonaUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 3 Oct 2011 (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.
Immunosuppressive drugs can be successfully withdrawn in a fraction of liver transplant patients. Specific peripheral blood gene expression markers can be employed to select patients with a high likelihood of being tolerant. In the current study the investigators propose to conduct a pilot non-randomized prospective study in which gradual weaning of immunosuppressive drugs will be offered to liver recipients exhibiting a favorable peripheral blood gene expression profile.
Detailed description
HYPOTHESIS We hypothesize that liver recipients exhibiting either specific gene expression and/or cell phenotypic markers in peripheral blood will be successfully weaned from all immunosuppressive drugs.
OBJECTIVE Evaluate the applicability of a set of non-invasive biomarkers in the identification of liver transplant recipients who can successfully discontinue all immunosuppressive therapy.
METODOLOGY
- Immunosuppression drug weaning: according to the clinical protocol approved, all patients will undergo liver biopsy before entry. Patients will be visited every 4 weeks, and immunosuppressive drugs will be gradually discontinued with the aim of achieving 50% decrease in drug dosages by month 3, and complete withdrawal by month 6 after initiation of the study. Following drug discontinuation, patients will continue to be followed every month until month 12 after initiation of the study. Liver function tests will be obtained at every clinical follow-up visit.
- Management of liver function test alterations: a) Increases in liver function tests below 2-fold normal levels for AST/ALT/GGT or 1.5-fold normal levels for ALP will result in no further decreases in drug dosages, and performance of new liver function tests in 14 days. Worsening or persistence of liver function test alterations will constitute indication for liver biopsy. b) Increases in liver function tests beyond 2-fold normal levels for AST/ALT/GGT or1.5-fold normal levels for ALP.
- Diagnosis of liver graft rejection: will be based on the finding of 2 out of 3 of the following histological criteria: portal inflammation, injury to bile duct epithelium, and endothelitis. The finding of a mixed portal/loblular lymphocytic infiltrate not attributable to any other cause and responding to an increase in immunosuppressive drug doses will also be considered as a rejection.
- Management of rejection episodes: patients presenting with mild to moderate acute rejection will be treated with 20 mg of prednisone in decreasing doses within 4 to 6 weeks. Patients with severe acute rejection will be admitted to hospital and treated with high dose IV prednisone (500-1000mg/day) during 3 day and thereafter oral prednisone at decreasing dose according to evolution of liver function tests. In every case patients will return to previous immunosuppressive dose enough to maintained normal or near normal liver function test.
SAMPLE SIZE According to our data, the success rate of an immunosuppression withdrawal strategy in stable liver transplant recipients transplanted for more than 3 year is 42% (these patients are consider as operationally tolerants). Our hypothesis is that with the use of biomarkers to identify potential tolerant patients the investigators will be able to increase the success rate of this strategy up to 78%. In order to achieve this success rate the sample size needed in this study is 25 patients (power 80% and significance of 95%).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Weaning patients | Experimental | Other: Immunosuppresion withdrawal |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Liver transplant recipients with at least 3 years of post-operative follow-up in whom gene expression pattern changed from non-tolerant to tolerant under sirolimus treatment.
- Feasibility of performing very frequent (every 2-3 weeks) clinical follow-up visits.
- No history of graft rejection during the previous 12 months.
- Basal liver biopsy without signs of rejection
- Stability of liver graft function, defined as: a) normal liver function tests (AST, ALT, ALP, GGT) during at least 6 months; or alternatively b) minor alterations in liver function tests that have not changed over the previous 6 months (AST/ALT < 2 fold normal levels; ALP < 1.5 fold normal levels; GGT < 2 fold normal levels; bilirubin < 2 mg/dL).
Key exclusion criteria (5 listed)
- Requirement of immunosuppressive treatment for an indication different to liver transplantation.
- Documented human immunodeficiency virus (HIV) infection.
- Liver-Kidney transplant recipients.
- History of liver autoimmune disease (autoimmune hepatitis, primary liver cirrhosis, primary sclerosing cholangitis)
- Active hepatitis C virus infection as defined by positive serum HCV-RNA.
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 |
|---|---|---|
| Immunosuppresion withdrawalAlso: Cyclosporine A, TacrolimusGradual discontinuation of all immunosuppressive drugs. | Other | Weaning patients |
Primary outcome
Proportion of patients developing operational tolerance
Time frame: 12 months after complete withdrawal of all immunosuppressive drugs
Results and safety
The study was stopped early (reason given: Insufficient recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2013.
Related trials for Liver Transplantation
Not yet recruitingObservational study
Prevalence and Development of Liver Dysfunction in Hematopoietic Stem Cell Transplant
Hematopoietic Stem Cell Transplant
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Not yet recruiting
New Biomarkers for Organ Viability Assessment During Hypothermic Machine Perfusion in Liver Transplantation: the Role of Extemporaneous Histological Examination.
Liver Transplantation (LT), Early Allograft Dysfunction
RecruitingPhase 2
Expanding Liver Transplant Immunosuppression Minimization Via Everolimus
Liver Transplant
RecruitingObservational study
Long-term Follow-up (LTFU) Study of Participants in Any iECURE Protocol Using an Investigational Product (IP)
Ornithine Transcarbamylase Deficiency, Ornithine Transcarbamylase Deficiency Disease
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.
Alberto Sanchez-Fueyo, MD principal investigator
Hospital Clinic of Barcelona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Immunosuppresion withdrawal in people with Liver Transplantation, run by Hospital Clinic of Barcelona 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 7 inclusion and 5 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 20 Dec 2013. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Insufficient recruitment). 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?
Proportion of patients developing operational tolerance (time frame: 12 months after complete withdrawal of all immunosuppressive drugs). 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 20 Dec 2013.