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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified April 2012 by Guerkan SENGOELGE, Medical University of Vienna.
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT00978965
First Posted: September 17, 2009
Last Update Posted: April 24, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Novartis
Information provided by (Responsible Party):
Guerkan SENGOELGE, Medical University of Vienna
  Purpose

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.


Condition Intervention Phase
Renal Transplantation Genetic: MPA SNP Phase 2

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Guerkan SENGOELGE, Medical University of Vienna:

Primary Outcome Measures:
  • Detection of functionally relevant SNPs in IMPDH 2 gene. [ Time Frame: 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 ]

Estimated Enrollment: 250
Study Start Date: October 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
All patients Genetic: MPA SNP
Functional relevant MPA SNP will be sought in patients DNA isolated from leucocytes

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients with a de novo kidney transplantation
Criteria

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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00978965


Contacts
Contact: Gürkan Sengölge, MD ++43-1-40400 ext 4389 guerkan.sengoelge@meduniwien.ac.at
Contact: Wolfgang Winnicki, MD ++43-1-40400 ext 2125 winnicki_wolfgang@gmx.at

Locations
Austria
Department of Medicine III, Division of Nephrology Recruiting
Vienna, Austria, A-1090
Contact: Gürkan Sengölge, MD    ++43-1-40400 ext 4389    guerkan.sengoelge@meduniwien.ac.at   
Principal Investigator: Gürkan Sengölge, MD         
Sponsors and Collaborators
Medical University of Vienna
Novartis
Investigators
Principal Investigator: Gürkan Sengölge, MD Medical University of Vienna
  More Information

Responsible Party: Guerkan SENGOELGE, Assoc. Prof. Priv.-Doz. Dr., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT00978965     History of Changes
Other Study ID Numbers: MPASNPVienna
First Submitted: September 14, 2009
First Posted: September 17, 2009
Last Update Posted: April 24, 2012
Last Verified: April 2012

Keywords provided by Guerkan SENGOELGE, Medical University of Vienna:
kidney transplantation
immunosuppression
single nucleotide polymorphism
IMPDH

Additional relevant MeSH terms:
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action