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

Completed

• Conditions: Renal Transplantation
• Interventions: Genetic: MPA SNP

• Registration Number: NCT00978965
• Lead Sponsor: Medical University of Vienna

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-09-14
• Study First Submitted QC: 2009-09-16
• Study First Posted: 2009-09-17
• Study Start: 2009-10
• Status Verified: 2020-09
• Primary Completion: 2020-09-09
• Study Completion: 2020-09-09
• Last Update Submitted: 2020-09-09
• Last Update Posted: 2020-09-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 277

Inclusion Criteria

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

Exclusion Criteria

• pregnancy
• panel of antigens reactivity > 40%

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
All patients	MPA SNP	-

Primary Outcome Measures

Name	Time	Method
Detection of functionally relevant SNPs in IMPDH 2 gene.	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	12 months per patient

Secondary Outcome Measures

Name	Time	Method
Screening for strongyloides IgG titers	12 months

Trial Locations

Locations (1)

Department of Medicine III, Division of Nephrology; 🇦🇹 Vienna, Austria