Identification of Patients With High Probability of Poorly Responding to Therapy With Mycophenolic Acid Prodrugs
|ClinicalTrials.gov Identifier: NCT00978965|
Recruitment Status : Active, not recruiting
First Posted : September 17, 2009
Last Update Posted : December 27, 2017
This study is designed to define groups of patients (among patients with a heart or kidney graft or a glomerular disease and nephrotic range proteinuria) who would either not profit from a therapy with mycophenolate-mofetil (MMF) or need a higher than conventional dose to respond.
Mainly there are 2 possible explanations for inter-patient differences in responsiveness to MMF therapy:
- Based on a mutation (in this study single nucleotide polymorphisms-SNPs-) in the inosine monophosphate dehydrogenase 2 (IMPDH 2) transcript as the target enzyme of mycophenolic acid (MPA) pathway, MMF cannot exert its effect.
- Based on a high enzyme activity of IMPDH 2 a higher MMF dose than in the conventional regimens is needed.
To study the significance of these possible explanations there are 4 objectives in this study:
Objective 1: Since there are no data on SNPs with functional relevance in IMPDH 2 transcript, we will first sequence all 14 exons of this gene in their entirety in 100 gender and age matched healthy individuals.
Objective 2: The functional relevance of a detected SNP will be tested in vitro in a lymphocyte proliferation assay using various MPA concentrations.
Objective 3: These functionally relevant SNPs will be searched in patients with kidney graft in a retrospective as well as prospective manner.
Objective 4: Parallel to the genotyping experiments, IMPDH 2 activity and MPA plasma levels will be measured in all patients recruited in the study prospectively.
An association between these SNPs or various IMPDH 2 activity / MPA plasma levels with MMF responsiveness will be examined.
Objective 5: Strongyloides IgG titers are screened to evaluate the prevalence of helminth carriers in patients with immunosuppressive therapy.
|Condition or disease||Intervention/treatment|
|Renal Transplantation||Genetic: MPA SNP|
|Study Type :||Observational|
|Estimated Enrollment :||250 participants|
|Official Title:||Identification of Patients With High Probability of Not or Poorly Responding to Mycophenolate-mofetil (Cellcept®) or Mycophenolate-natrium (Myfortic®) Therapy|
|Study Start Date :||October 2009|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
Genetic: MPA SNP
Functional relevant MPA SNP will be sought in patients DNA isolated from leucocytes
- Detection of functionally relevant SNPs in IMPDH 2 gene. [ Time Frame: 6 months ]
- The association of detected SNPs in inosine monophosphate dehydrogenase-2 transcript or high IMPDH 2 activity with the lack of response to MPA therapy defined as - number of biopsy proven acute rejections in the first year after transplantation [ Time Frame: 12 months per patient ]
- Screening for strongyloides IgG titers [ Time Frame: 12 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00978965
|Department of Medicine III, Division of Nephrology|
|Vienna, Austria, A-1090|
|Principal Investigator:||Gürkan Sengölge, MD||Medical University of Vienna|