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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 because the information has not been verified recently.
Verified April 2012 by Medical University of Vienna.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Guerkan SENGOELGE, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00978965
First received: September 14, 2009
Last updated: April 23, 2012
Last verified: April 2012
  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 Medical University of Vienna:

Primary Outcome Measures:
  • Detection of functionally relevant SNPs in IMPDH 2 gene. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided

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
Study First Received: September 14, 2009
Last Updated: April 23, 2012
Health Authority: Austria: Agency for Health and Food Safety

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

ClinicalTrials.gov processed this record on November 27, 2014