NCT01321112

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Feb 2011

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2011

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 22, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 23, 2011

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
Last Updated

May 10, 2012

Status Verified

May 1, 2012

Enrollment Period

3.1 years

First QC Date

March 22, 2011

Last Update Submit

May 8, 2012

Conditions

Gene ExpressionImmunosuppression ConversionLiver Transplantation

Keywords

ConversionMycophenolate mofetilCalcineurin inhibitorsLiver transplantationGene expression

Outcome Measures

Primary Outcomes (1)

  • Diagnostic accuracy of transcriptional biomarkers

    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.

    48 weeks

Secondary Outcomes (6)

  • Renal function improvement

    48 weeks

  • Frequency of regulatory cells

    48 weeks

  • Blood pressure

    48 weeks

  • Total cholesterol reduction

    48 weeks

  • Uric acid reduction

    48 weeks

  • +1 more secondary outcomes

Study Arms (1)

Conversion arm

EXPERIMENTAL

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

Interventions

conversion from CNI to MMFDRUG

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.

Also known as: Conversion
Conversion arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • total white cell count ≤ 2 x 109/L
  • hemoglobin \< 7.0 g/L
  • platelet count ≤ 50x x 109/L
  • systemic infection requiring therapy
  • pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Gastroenterology Department, Pontificia Universidad Catolica de Chile

Santiago, Santiago, RM, 8330024, Chile

RECRUITING

Related Publications (6)

  • Mells G, Neuberger J. Long-term care of the liver allograft recipient. Semin Liver Dis. 2009 Feb;29(1):102-20. doi: 10.1055/s-0029-1192059. Epub 2009 Feb 23.

    PMID: 19235663BACKGROUND

  • Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007 Dec 20;357(25):2601-14. doi: 10.1056/NEJMra064928. No abstract available.

    PMID: 18094380BACKGROUND

  • Martinez-Llordella M, Lozano JJ, Puig-Pey I, Orlando G, Tisone G, Lerut J, Benitez C, Pons JA, Parrilla P, Ramirez P, Bruguera M, Rimola A, Sanchez-Fueyo A. Using transcriptional profiling to develop a diagnostic test of operational tolerance in liver transplant recipients. J Clin Invest. 2008 Aug;118(8):2845-57. doi: 10.1172/JCI35342.

    PMID: 18654667BACKGROUND

  • Demirkiran A, Sewgobind VD, van der Weijde J, Kok A, Baan CC, Kwekkeboom J, Tilanus HW, Metselaar HJ, van der Laan LJ. Conversion from calcineurin inhibitor to mycophenolate mofetil-based immunosuppression changes the frequency and phenotype of CD4+FOXP3+ regulatory T cells. Transplantation. 2009 Apr 15;87(7):1062-8. doi: 10.1097/TP.0b013e31819d2032.

    PMID: 19352129BACKGROUND

  • Farkas SA, Schnitzbauer AA, Kirchner G, Obed A, Banas B, Schlitt HJ. Calcineurin inhibitor minimization protocols in liver transplantation. Transpl Int. 2009 Jan;22(1):49-60. doi: 10.1111/j.1432-2277.2008.00796.x.

    PMID: 19121146BACKGROUND

  • Norero B, Serrano CA, Sanchez-Fueyo A, Duarte I, Torres J, Ocquetau M, Barrera F, Arrese M, Soza A, Benitez C. Conversion to mycophenolate mofetil monotherapy in liver recipients: Calcineurin inhibitor levels are key. Ann Hepatol. 2017 Jan-Feb 2017;16(1):94-106. doi: 10.5604/16652681.1226820.

    PMID: 28051798DERIVED

Study Officials

  • Carlos E Benitez, MD

    Gastroenterology Department. Pontificia Universidad Católica de Chile

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Carlos E Benitez, MD

CONTACT

56-02-3543820cbenitez@med.puc.cl

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 22, 2011

First Posted

March 23, 2011

Study Start

February 1, 2011

Primary Completion

March 1, 2014

Study Completion

March 1, 2014

Last Updated

May 10, 2012

Record last verified: 2012-05

Locations

CL(1)