Liver Transplantation Clinical Trial
— TBCPOfficial title:
Search for Transcriptional Biomarkers in a Conversion Protocol From Calcineurin Inhibitors to Mycophenolate Mofetil Monotherapy
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.
Status | Recruiting |
Enrollment | 40 |
Est. completion date | March 2014 |
Est. primary completion date | March 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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 |
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Country | Name | City | State |
---|---|---|---|
Chile | Gastroenterology Department, Pontificia Universidad Catolica de Chile | Santiago | Santiago, RM |
Lead Sponsor | Collaborator |
---|---|
Pontificia Universidad Catolica de Chile |
Chile,
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. — View Citation
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. Review. — View Citation
Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007 Dec 20;357(25):2601-14. Review. — View Citation
Martínez-Llordella M, Lozano JJ, Puig-Pey I, Orlando G, Tisone G, Lerut J, Benítez C, Pons JA, Parrilla P, Ramírez P, Bruguera M, Rimola A, Sánchez-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. — View Citation
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. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | No |
Secondary | Renal function improvement | 20% of improvement on baseline serum creatinine compared to the serum creatinine at the end of the study. | 48 weeks | No |
Secondary | Frequency of regulatory cells | The frequency of regulatory cells (CD4+FoxP3+ T cells) will be measured at baseline and at the end of the study. | 48 weeks | No |
Secondary | Blood pressure | Reduction of baseline blood presure at the end of the study (48 weeks) | 48 weeks | No |
Secondary | Total cholesterol reduction | Reduction of baseline serum cholesterol at the end of the study. | 48 weeks | No |
Secondary | Uric acid reduction | Reduction of baseline uric acid serum level at the end of the study. | 48 weeks | No |
Secondary | Reduction of glycosylated haemoglobin | Reduction of baseline glycosylated haemoglobin at the end of study. | 48 weeks | No |
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