Trial document




drksid header

  DRKS00000292

Trial Description

start of 1:1-Block title

Title

Proposal for a prospective observational study of patients with atypical SCID

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

Atypical SCID

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

http://www.pcid-study.org

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

In recent years it has increasingly been recognized that some mutations in genes associated with a Severe Combined Immunodeficiency (SCID)-phenotype can also cause milder forms of immunodeficiencies. These hypomorphic mutations allow residual and variable function of the affected gene product and therefore lead to highly variable residual immunity. T cells are usually present at low numbers in these patients, but may even be increased in some cases. As a result, the clinical and immunological phenotype of patients with hypomorphic mutations in SCID-causing genes ("atypical SCID") is broad. The patients usually present with a later onset of immunodeficiency and less severe susceptibility to infections. Most importantly, they frequently manifest symptoms of immune dysregulation including eczematous skin lesions, high IgE, lymphoproliferation, granuloma formation, colitis and autoimmune diseases, mostly autoimmune cytopenias. Different mutations in one SCID-causing gene can therefore lead to a wide spectrum of clinical manifestations. In the proposed study we would like to address the following questions:
1. Identification of reasonable therapy options for patients with "atypical" SCID.
2. Analysis of BMT rates/survival rates over the time. BMT vs. supportive therapy.
3. Identification of patterns of clinical and immunological presentation of patients with "atypical" SCID (validation of findings based on the retrospective analysis).

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

In recent years it has increasingly been recognized that some mutations in genes associated with a Severe Combined Immunodeficiency (SCID)-phenotype can also cause milder forms of immunodeficiencies. These hypomorphic mutations allow residual and variable function of the affected gene product and therefore lead to highly variable residual immunity. T cells are usually present at low numbers in these patients, but may even be increased in some cases. As a result, the clinical and immunological phenotype of patients with hypomorphic mutations in SCID-causing genes ("atypical SCID") is broad. The patients usually present with a later onset of immunodeficiency and less severe susceptibility to infections. Most importantly, they frequently manifest symptoms of immune dysregulation including eczematous skin lesions, high IgE, lymphoproliferation, granuloma formation, colitis and autoimmune diseases, mostly autoimmune cytopenias. Different mutations in one SCID-causing gene can therefore lead to a wide spectrum of clinical manifestations. In the proposed study we would like to address the following questions:
1. Identification of reasonable therapy options for patients with "atypical" SCID.
2. Analysis of BMT rates/survival rates over the time. BMT vs. supportive therapy.
3. Identification of "patterns" of clinical and immunological presentation of patients with "atypical" SCID (validation of findings based on the retrospective analysis).

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00000292
  •   2010/01/25
  •   [---]*
  •   yes
  •   Approved
  •   412/09, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   U1111-1113-4807 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   D81.9 -  Combined immunodeficiency, unspecified
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   cohort study with data collection and maybe collection of biomaterials
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Non-interventional
  •   Epidemiological study
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Prognosis
  •   Single (group)
  •   N/A
  •   N/A
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

prevalence of each clinical and immunological feature in the full cohort of patients with atypical SCID

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

percentage of patients with normal numbers of T-, B- and NK- or naïve T cells, nomal levels of immunoglobulins or specific antibodies in order to further emphasize the observation that these results do not exclude the diagnosis of SCID || Time to BMT, survival time

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
  •   United Kingdom
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • [---]*
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2010/07/31
  •   50
  •   Multicenter trial
  •   International
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   no minimum age
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

1. All Patients with biallelic mutations in a gene where complete loss of function always leads to a SCID phenotype (that is RAG1/2, Artemis, IL-2R-alpha, IL7-R-gamma, DNA Ligase IV, JAK3, ADA) are eligible for this study.

2. T-cells (CD3+) > 100/µl. This threshhold is arbitrarily chosen as indicative of residual function of the affected gene product.

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

1. Patients with mutations in the following "SCID" genes due to the presence of T cells in a significant proportion of patients with null mutations: Fox N1 (WHN), CD45, CD3 (delta, epsilon, gamma, theta), Cernunnous, Coronin A1, Orai-1, ZAP-70, MHC II, RMRP, PNP and del22q.11. Patients with mutations in AK2 are also excluded.

2. Maternal T-cells (this must be investigated for a patient to be included)

3. Clinical presentation of "classical" SCID:
a.) Opportunistic infections (e.g. PCP-related pneumonia, invasive fungal infections, mycobacterial infections) in the first year of life
b.) Severe infections (major-infections) combined with failure to thrive, respectively persistent (> 4 weeks)/ invasive Candida infection in the first year of life

4. Clinical presentation of Omenn syndrome:
(e.g. erythematous rash, lymphoproliferation, severe/opportunistic infections, failure to thrive in the first year of life)

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Centrum für Chronische Immmundefizienz (CCI)
    • Mr.  Prof. Dr. med.  Stephan  Ehl 
    • Breisacher Str. 117 2. OG
    • 79106  Freiburg
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Centrum für Chronische Immmundefizienz (CCI)
    • Mr.  Prof. Dr. med.  Stephan  Ehl 
    • Breisacher Str. 117 2. OG
    • 79106  Freiburg
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Universitätsklinikum FreiburgCentrum für Chronische Immundefizienz (CCI)
    • Mr.  Dr. med.  Carsten  Speckmann 
    • Mathildenstr.
    • 79106  Freiburg
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Centrum für Chronische Immmundefizienz (CCI)
    • Mr.  Prof. Dr. med.  Stephan  Ehl 
    • Freiburg
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting complete, follow-up complete
  •   2011/07/31
end of 1:1-Block state
* This entry means the parameter is not applicable or has not been set.