Trial document





This trial has been registered retrospectively.
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  DRKS00013746

Trial Description

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Title

Genetic factors for the pathogenesis of kidney stones, nephrocalcinosis and related disturbances of urine composition

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Trial Acronym

GeFaSto

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URL of the Trial

http:///

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Brief Summary in Lay Language

Kidney stone disorders are among the most common health problems in industrialized countries and contribute to the development of chronic renal failure. The consequences for those affected and the society are far-reaching; in health, social and economic terms. The underlying molecular disorder in patients with renal stone disease, nephrocalcinosis and / or hypercalciuria is often unknown.
Complete mutational analysis in over 35 known disease genes in a larger cohort of patients was very costly and difficult to achieve using the available engineering methods until recently. The introduction of novel amplification and next-generation sequencing methods has changed the situation over the last few years. In collaboration with the laboratory of Prof. Friedhelm Hildebrandt (Boston Children's Hospital / Harvard Medical School), we have developed and implemented a novel high-throughput method, which we now for the first time in a German cohort with kidney stone disease, nephrocalcinosis and / or hypercalciuria Want to use. In a pilot project with approximately 100 predominantly adult patients it could be shown that the prevalence of monogenic forms of disease seems to be higher than previously assumed. Accordingly, the hypothesis has been formulated that the presence of hypomorphic mutations is a determinant of kidney stone disease, nephrocalcinosis and / or hypercalciuria in adulthood.
The findings will help to understand the pathogenesis of renal stone disease, nephrocalcinosis and hypercalciuria. In the future, we expect to identify a risk prognosis for the development of chronic renal insufficiency based on identified mutations.

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Brief Summary in Scientific Language

Using a novel high-throughput mutation analysis, we want to test DNA from patients with kidney stones, nephrocalcinosis and / or hypercalciuria for mutations in genes that have a known association with renal stone disease, nephrocalcinosis and related urinary disorders. In addition, we would like to identify new genes that might be related to the phenotype mentioned. The exact proportion of genetically determined kidney stone disease and related disorders (especially in adults) has been poorly understood. The reason for this is that the complete mutation analysis has so far been too costly and often unavailable to the patient. Nevertheless, kidney stones and related disorders contribute significantly to the development of chronic renal failure. Now it will be investigated how high the proportion of a monogenic disposition (no detectable pathogenic variant vs. hypomorphic mutation vs. 0 mutation) lies in the respective age group. In addition, in cases without detectable pathogenic variant in known disease genes, a mutation analysis should be carried out in novel candidate genes. The DNA of the patients should be stored and used for future investigations of previously unknown genes. The findings will contribute to the understanding of the pathogenesis of renal stone disease, nephrocalcinosis and hypercalciuria and potentially enable individualized therapy. Additional patient examinations will not be required, all we need is a blood sample for DNA extraction and, where appropriate, cell harvesting for immortalization for further functional studies of the relevance of a mutation.

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Organizational Data

  •   DRKS00013746
  •   2018/02/08
  •   [---]*
  •   yes
  •   Approved
  •   159/14-ff, Ethikkommission an der Medizinischen Fakultät der Universität Leipzig
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Secondary IDs

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Health Condition or Problem studied

  •   kidney stone suffer, nephrocalcinosis
  •   N20.0 -  Calculus of kidney
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Interventions/Observational Groups

  •   Genetic analysis to investigate relationships between certain mutations and renal stone disease.
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Pharmacogenetics
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Identification of a mutation in a known disease gene and correlation with the clinical phenotype.

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Secondary Outcome

Identification of so far uncharacterized genes.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2017/03/01
  •   200
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   no minimum age
  •   no maximum age
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Additional Inclusion Criteria

Patients with renal stone disease, nephrocalcinosis and / or hypercalciuria.

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Exclusion Criteria

Patients with known causative genetic or non-genetic causative disease.

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Addresses

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    • Universitätsklinik Leipzig, Department für Innere Medizin, Neurologie und Dermatologie, Klinik für Endokrinologie und Neprhologie
    • Liebigstraße 20
    • 04103  Leipzig
    • Germany
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    • Martin-Luther-Universität Halle-Wittenberg,Universitätsklinikum Halle
    • Ms.  Prof. Dr. med.  Katrin  Hoffmann 
    • Magdeburger Str. 2
    • 06112  Halle
    • Germany
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    •   +49 (0)345-557 4292
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    • Klinik für Endokrinologie und Nephrologie
    • Mr.  PD Dr. med.  Jan  Halbritter 
    • Leibigstr. 20
    • 04103  Leipzig
    • Germany
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    •   0341/9713812
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    • UKF Freiburg
    • Mr.  Dr.  Dominik  Schöb 
    • Hugstetter Str. 55
    • 79106  Freiburg
    • Germany
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    • UKF Freiburg
    • Mr.  Dr.  Dominik  Schöb 
    • Hugstetter Str. 55
    • 79106  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Universitätsklinik Freiburg
    • 79106  Freiburg
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.