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

NCT ID: NCT00978965

Last Updated: 2020-09-10

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 277 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2020-09-09

Brief 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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

All patients

MPA SNP

Intervention Type: GENETIC

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

Interventions

MPA SNP

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

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• patients with a de novo kidney graft and age >18 and < 75

Exclusion Criteria

• pregnancy
• panel of antigens reactivity > 40%

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Guerkan SENGOELGE

Assoc. Prof. Priv.-Doz. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gürkan Sengölge, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Department of Medicine III, Division of Nephrology

Vienna, , Austria

Countries

Austria

Other Identifiers

MPASNPVienna

Identifier Type: -

Identifier Source: org_study_id