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

NCT00978965 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 277

Last updated 2020-09-10

No results posted yet for this study

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

GENETIC

MPA SNP

Functional relevant MPA SNP will be sought in patients DNA isolated from leucocytes

Sponsors & Collaborators

  • Novartis

    collaborator INDUSTRY

  • Medical University of Vienna

    lead OTHER

Principal Investigators

  • Gürkan Sengölge, MD · Medical University of Vienna

Eligibility

Min Age
18 Years
Max Age
75 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2009-10-31
Primary Completion
2020-09-09
Completion
2020-09-09

Countries

  • Austria

Study Locations

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Entities

Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00978965 on ClinicalTrials.gov