NCT00978965

Identification of Patients With High Probability of Poorly Responding to Therapy With Mycophenolic Acid Prodrugs

Identification of Patients With High Probability of Not or Poorly Responding to Mycophenolate-mofetil (Cellcept®) or Mycophenolate-natrium (Myfortic®) Therapy

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 277 (actual)
• Sponsor: Medical University of Vienna · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Accepted

Summary

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: 1. 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. 2. 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.

Conditions

• Renal Transplantation

Interventions

Type	Name	Description
GENETIC	MPA SNP	Functional relevant MPA SNP will be sought in patients DNA isolated from leucocytes

Timeline

• Start date: 2009-10-01
• Primary completion: 2020-09-09
• Completion: 2020-09-09
• First posted: 2009-09-17
• Last updated: 2020-09-10

Locations

1 site across 1 country: Austria