Text Size

Search for Transcriptional Biomarkers in a Conversion Protocol From Calcineurin Inhibitors to Mycophenolate Mofetil (TBCP)

This study is currently recruiting participants.
Verified May 2012 by Pontificia Universidad Catolica de Chile
Sponsor:
Information provided by (Responsible Party):
Pontificia Universidad Catolica de Chile
ClinicalTrials.gov Identifier:
NCT01321112
First received: March 22, 2011
Last updated: May 8, 2012
Last verified: May 2012
History of Changes
  Purpose

As is well known, immunosuppressive treatment (IS) after liver transplantation has several and frequents adverse effects that limit the survival of the graft and recipients. Because of that, it is desirable that these recipients were able to receive a mild IS regime with a better safety profile. An attempt to get that aim has been evaluated in several trials in the past, and consist in to change the IS regime from an calcineurin inhibitors (CNI) based to another less intense and with less adverse effects based on mycophenolate mofetil (MMF), which is known to have a better safety profile. The success rate of this strategy(i.e. complete conversion in absence of rejection) has a wide range from 100% to 50% approximately. However it is accepted that this strategy is associated with the improvement of several adverse effects of CNIs such as renal failure and dyslipemia. This study's aim is to perform IS conversion from CNI to MMF monotherapy and look for transcriptional biomarkers employing a whole genome expression study performed with microarrays at baseline on liver tissue and/or PBMCs to try to find a differential gene expression able to correlate with a successful conversion and thus, to generate a set of transcriptional biomarkers potentially able to predict the result of the IS conversion on an independent cohort of liver recipients.


Condition Intervention
Gene Expression
Immunosuppression Conversion
Liver Transplantation
 Drug: conversion from CNI to MMF

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Search for Transcriptional Biomarkers in a Conversion Protocol From Calcineurin Inhibitors to Mycophenolate Mofetil Monotherapy

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Pontificia Universidad Catolica de Chile:

Primary Outcome Measures:
  • Diagnostic accuracy of transcriptional biomarkers [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Whole genome expresion study by microarrays will be use to determine the correlation between succesful conversion (yes/no) and the expression level of the most informative genes.


Secondary Outcome Measures:
  • Renal function improvement [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    20% of improvement on baseline serum creatinine compared to the serum creatinine at the end of the study.

  • Frequency of regulatory cells [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    The frequency of regulatory cells (CD4+FoxP3+ T cells) will be measured at baseline and at the end of the study.

  • Blood pressure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Reduction of baseline blood presure at the end of the study (48 weeks)

  • Total cholesterol reduction [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Reduction of baseline serum cholesterol at the end of the study.

  • Uric acid reduction [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Reduction of baseline uric acid serum level at the end of the study.

  • Reduction of glycosylated haemoglobin [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Reduction of baseline glycosylated haemoglobin at the end of study.


Estimated Enrollment: 40
Study Start Date: February 2011
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Conversion arm
After screening procedure mycophenolate mofetil will be started (week -4) at a dose of 500 mg twice a day for two weeks and then (week -2) increased to 1000 mg twice a day and CNI will be reduced at the 50% of the initial dose. After two weeks (week 0) CNI will be completely discontinued (complete IS conversion). The investigators will follow up patients every 4 weeks up to 48 weeks after the complete IS conversion.
 Drug: conversion from CNI to MMF
After screening procedure mycophenolate mofetil will be started (week -4) at a dose of 500 mg twice a day for two weeks and then (week -2) increased to 1000 mg twice a day and CNI will be reduced at the 50% of the initial dose. After two weeks (week 0) CNI will be completely discontinued (complete IS conversion). The investigators will follow up patients every 4 weeks up to 48 weeks after the complete IS conversion.
Other Name: Conversion

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Liver transplantation more than 2 years ago
  • Stable graft function
  • No history of autoimmune liver disease
  • Absence of rejection in the last 12 months
  • IS regime: calcineurin inhibitors (CNI) as monotherapy
  • Absence of rejection in the baseline liver biopsy
  • Signature of the informed consent form

Exclusion Criteria:

  • total white cell count ≤ 2 x 109/L
  • hemoglobin < 7.0 g/L
  • platelet count ≤ 50x x 109/L
  • systemic infection requiring therapy
  • pregnancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01321112

Contacts
Contact: Carlos E Benitez, MD 56-02-3543820 ext 3880 cbenitez@med.puc.cl

Locations
Chile
Gastroenterology Department, Pontificia Universidad Catolica de Chile Recruiting
Santiago, Santiago, RM, Chile, 8330024
Contact: Carlos E Benitez, MD     56-02-3543820 ext 3880     cbenitezc@med.puc.cl    
Sponsors and Collaborators
Pontificia Universidad Catolica de Chile
Investigators
Principal Investigator: Carlos E Benitez, MD Gastroenterology Department. Pontificia Universidad Católica de Chile
  More Information

Publications:

Responsible Party: Pontificia Universidad Catolica de Chile
ClinicalTrials.gov Identifier: NCT01321112     History of Changes
Other Study ID Numbers: 10-071
Study First Received: March 22, 2011
Last Updated: May 8, 2012
Health Authority: Chile: Comisión Nacional de Investigación Científica y Tecnológica

Keywords provided by Pontificia Universidad Catolica de Chile:
Conversion
Mycophenolate mofetil
Calcineurin inhibitors
Liver transplantation
Gene expression

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
 Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013