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

September 9, 2020 updated by: Guerkan SENGOELGE, Medical University of Vienna

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

277

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, A-1090
        • Department of Medicine III, Division of Nephrology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with a de novo kidney transplantation

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • pregnancy
  • panel of antigens reactivity > 40%

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
All patients
Genetic: MPA SNP
Functional relevant MPA SNP will be sought in patients DNA isolated from leucocytes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Detection of functionally relevant SNPs in IMPDH 2 gene.
Time Frame: 6 months
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
Time Frame: 12 months per patient
12 months per patient

Secondary Outcome Measures

Outcome Measure
Time Frame
Screening for strongyloides IgG titers
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Collaborators

Novartis

Investigators

  • Principal Investigator: Gürkan Sengölge, MD, Medical University of Vienna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (Actual)

September 9, 2020

Study Completion (Actual)

September 9, 2020

Study Registration Dates

First Submitted

September 14, 2009

First Submitted That Met QC Criteria

September 16, 2009

First Posted (Estimate)

September 17, 2009

Study Record Updates

Last Update Posted (Actual)

September 10, 2020

Last Update Submitted That Met QC Criteria

September 9, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • MPASNPVienna

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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