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

Renal Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00978965
• Other study ID #: MPASNPVienna
• Status: Completed
• Start date: October 2009
• Est. completion date: September 9, 2020

Study information

• Verified date: September 2020
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 277
• Est. completion date: September 9, 2020
• Est. primary completion date: September 9, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• pregnancy

• panel of antigens reactivity > 40%

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

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

Locations

Country	Name	City	State
Austria	Department of Medicine III, Division of Nephrology	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Vienna	Novartis

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detection of functionally relevant SNPs in IMPDH 2 gene.		6 months
Primary	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	Screening for strongyloides IgG titers		12 months