Trial document

This trial has been registered retrospectively.
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Trial Description

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Patients with mutations in the XIAP/BIRC4 gene

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Trial Acronym


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URL of the Trial

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Brief Summary in Lay Language

Scientific study which investigates the functional consequences of mutations in the BIRC4 gene in XIAP deficient patients. The spectrum of clinical features we are interested in includes haemophagocytic lymphohistiocytosis (HLH), inflammatory bowel disease (e.g. Crohn-like disese), unexplained splenomegaly with and without hypogammaglobulinemia, periodic fevers or prolonged mononucleosis.Through functional analysis of the mutated XIAP molecule we aim to understand how the XIAP molecule works in vivo and which XIAP dependent signalling pathways are important in human immune cells. To study the impact of disease associated mutations in BIRC4 on the signals sent when NOD2 and RIG-I are activated, we use cells from affected patients. This enables us to obtain detailed information regarding the molecular consequence of the mutations. By obtaining detailed information about what happens to the XIAP protein when it is mutated and how this affects the processes in which XIAP functions, we hope to obtain understanding of what goes “wrong” in the immune cells of affected patients. On the long run, this can reveal which processes in the cell could be targeted to counterbalance the defects caused by BIRC4 mutations for future treatment. The following centers are involved: CCI Freiburg (cohort coordination and immunological diagnostics), Children's Hospital University Hamburg (genetics), Department for Transfusion Medicine, University Hospital Ulm (genetics) and Department of Disease Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen (functional XIAP analysis)

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Brief Summary in Scientific Language

Expression und Funktion des XIAP Moleküls in Patienten mit Mutationen in BIRC4

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Organizational Data

  •   DRKS00004592
  •   2013/01/25
  •   [---]*
  •   yes
  •   Approved
  •   143/12, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   D82.3 -  Immunodeficiency following hereditary defective response to Epstein-Barr virus
  •   K50.9 -  Crohn's disease, unspecified
  •   D80.0 -  Hereditary hypogammaglobulinaemia
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Interventions/Observational Groups

  •   Patients with XLP, M. Crohn, EBV-infection, splenomegaly, hypogammaglobulinaemia and/or other symptoms for which a mutation in the gene BIRC4/XIAP was diagnosed. Enrolled patients will receive a venipuncture. Isolated patients cells are then flow cytometrically and genetically analyzed. Moreover, we establish cell lines to perform signalling pathway studies.
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  •   Non-interventional
  •   Other
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Diagnostic
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Influence of different mutations in XIAP/BIRC4 on intracellular signalling

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Secondary Outcome

Not applicable

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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  •   Actual
  •   2012/05/21
  •   30
  •   Monocenter 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 XLP-2 disease for whom a mutation in gene BIRC4/XIAP was diagnosed
- signed consent from the patient/parents for underaged patients

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Exclusion Criteria

- lack of signed consent from the patient/parents for underaged patients

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Sources of Monetary or Material Support

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  •   Recruiting complete, follow-up complete
  •   2015/06/30
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Trial Publications, Results and other Documents

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