Identification of Patients With High Probability of Poorly Responding to Therapy With Mycophenolic Acid Prodrugs
Recruitment status was Recruiting
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.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Identification of Patients With High Probability of Not or Poorly Responding to Mycophenolate-mofetil (Cellcept®) or Mycophenolate-natrium (Myfortic®) Therapy|
- Detection of functionally relevant SNPs in IMPDH 2 gene. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||June 2013|
|Estimated Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
Genetic: MPA SNP
Functional relevant MPA SNP will be sought in patients DNA isolated from leucocytes
Please refer to this study by its ClinicalTrials.gov identifier: NCT00978965
|Contact: Gürkan Sengölge, MD||++43-1-40400 ext firstname.lastname@example.org|
|Contact: Wolfgang Winnicki, MD||++43-1-40400 ext email@example.com|
|Department of Medicine III, Division of Nephrology||Recruiting|
|Vienna, Austria, A-1090|
|Contact: Gürkan Sengölge, MD ++43-1-40400 ext 4389 firstname.lastname@example.org|
|Principal Investigator: Gürkan Sengölge, MD|
|Principal Investigator:||Gürkan Sengölge, MD||Medical University of Vienna|