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

Sponsor
Medical University of Vienna (Other)
Overall Status
Completed
CT.gov ID
NCT00978965
Collaborator
Novartis (Industry)
277
1
131.3
2.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Genetic: MPA SNP

Study Design

Study Type:
Observational
Actual Enrollment :
277 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Identification of Patients With High Probability of Not or Poorly Responding to Mycophenolate-mofetil (Cellcept®) or Mycophenolate-natrium (Myfortic®) Therapy
Study Start Date :
Oct 1, 2009
Actual Primary Completion Date :
Sep 9, 2020
Actual Study Completion Date :
Sep 9, 2020

Arms and Interventions

Arm Intervention/Treatment
All patients

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

Outcome Measures

Primary Outcome Measures

  1. Detection of functionally relevant SNPs in IMPDH 2 gene. [6 months]

  2. 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

  1. Screening for strongyloides IgG titers [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • patients with a de novo kidney graft and age >18 and < 75
Exclusion Criteria:
  • pregnancy

  • panel of antigens reactivity > 40%

Contacts and Locations

Locations

Site City State Country Postal Code
1 Department of Medicine III, Division of Nephrology Vienna Austria A-1090

Sponsors and Collaborators

  • Medical University of Vienna
  • Novartis

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Guerkan SENGOELGE, Assoc. Prof. Priv.-Doz. Dr., Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00978965
Other Study ID Numbers:
  • MPASNPVienna
First Posted:
Sep 17, 2009
Last Update Posted:
Sep 10, 2020
Last Verified:
Sep 1, 2020
Keywords provided by Guerkan SENGOELGE, Assoc. Prof. Priv.-Doz. Dr., Medical University of Vienna

Study Results

No Results Posted as of Sep 10, 2020