Trial document





This trial has been registered retrospectively.
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  DRKS00012862

Trial Description

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Title

Clinical and Immunological Categorization of Pulmonary Aspergillosis in Cystic Fibrosis

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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Brief Summary in Scientific Language

Cystic fibrosis (CF) is the most common lethal genetic disease in Caucasians and affects approximately 70,000 people worldwide.
The leading cause of death is the progressive lung disease, driven by a complex and diverse inflammatory immune syndrome induced by recurrent and chronic bacterial and fungal infections of the lung.
The pathologic contribution of Aspergillus fumigatus (Af) becomes increasingly important for patients with CF.

There are different pulmonary Aspergillosis stages and for clinicians it is often difficult to reliably detect Af, to differentiate between Af related lung colonization, allergic sensitization, Af bronchitis, clinically proven ABPA, and lung infection and to clinically manage the relevant disease.

The host-Aspergillus interaction has been already described for patients with Allergic Bronchopulmonary Aspergillosis (ABPA) but for other indications results are poor.

Consensus guidelines for the management of ABPA in patients with CF exist, but not for the diagnosis of other Aspergillosis categories such as Af colonization, Aspergillus bronchitis, Aspergillus pneumonia, and aspergilloma and respective therapeutic strategies.

With this study we want to initially identify and evaluate intrinsic determinants predicting distinct pulmonary Aspergillosis stages.
Only with a clear categorization of Aspergillosis stage adequate therapy decisions are possible in the proposed patient cohort.

We expect to screen approximately 200 patients with CF and will enroll eligible patients after written consent in this prospective cohort study

Patient’s samples (sputum, blood, BAL) will be analyzed to identify clinically useful immunologic markers as stage-specific Aspergillosis markers and lung function/LCI will be collected and selected to determine lung function changes in treated patients with Aspergillosis based on each of the above mentioned Aspergillosis stages

Our objectives are:
1) Diagnosis of distinct Aspergillosis stages according to proposed diagnostic program
2) Identification of microbiological and immunological determinants of Aspergillosis-specific signatures in patients with CF.
3) Characterization of pathogen-Af interaction

The knowledge of these categorization factors is the key catalyst for accelerated identification and effective treatment of patients with CF at risk for Aspergillosis.

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Organizational Data

  •   DRKS00012862
  •   2017/09/04
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  •   yes
  •   Approved
  •   EA2/121/16, Ethik-Kommission der Charité -Universitätsmedizin Berlin-
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Secondary IDs

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Health Condition or Problem studied

  •   E84 -  Cystic fibrosis
  •   B44 -  Aspergillosis
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Interventions/Observational Groups

  •   We will screen patients with CF and will enroll eligible patients after written consent in this prospective cohort study.

    A medical history questionnaire will be completed and patient samples (sputum, blood) and lung function will be collected and selected during annual and 3-monthly control check-ups or during a hospital stay.

    We will test the following parameters at the first visit and after one year:
    - Sputum: fungal culture, Galactomannann antigen test, qPCR 2
    - Blood: CRP, total IgE, Af specific IgE, Af specific IgG, total IgG.; T-cell reactivity of the fungal proteins
    - lung function: FEV1, FVC and MEF25
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Characteristics

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

Clinical confirmation of 6 distinct pulmonary aspergillosis stages:
1)Af Colonization
2)Af Sensitization1)
3)Non-allergic bronchopulmonary aspergillosis (Af bronchitis)
4)Allergic bronchopulmonary aspergillosis (ABPA)
5)Invasive pulmonary aspergillosis (Af-pneumonia)
6)Aspergilloma (chronic pulmonary aspergillosis)

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Secondary Outcome

- Lung function changes based on each of the above mentioned aspergillosis stages

- Validated new biomarker(s) indicative for
1) Af Colonization: Af in sputum, qPCR
2) Af Sensitization: Af specific IgG and IgE, Galctomannan Index.
3) Af bronchitis: qPCR in sputum, no increased IgE
4) ABPA: total IgE, Af specific IgE, sputum, Galactomannan Index.
5) Af-pneumonia: T-cell reactivity of the fungal proteins
6) Aspergilloma: sputum, radiological imaging

- Characterization of pathogen-Af interaction

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2017/01/19
  •   200
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   6   Years
  •   70   Years
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Additional Inclusion Criteria

-Provide written informed consent
- Confirmed diagnosis of CF
- Aged between 6 and 70 years
- Ability to do a lung function test and to provide sputum samples for microbiological evaluation

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Exclusion Criteria

Participants will not be entered in the study for any of the following exclusion criteria:
- Patients unable to sign informed consent or unwilling to comply with the procedural
requirements of this clinical protocol.
- No ability to do a lung function test and to provide sputum samples for microbiological evaluation.
- Not possible to take blood

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Addresses

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    • Charite Universitätsmedizin Berlin
    • Mr.  Dr  Carsten  Schwarz 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Charité Universitätsmedizin Berlin Klinik für Pädiatrie m.S. Pneumologie und Immunologie Christiane Herzog Zentrum Berlin
    • Mr.  Dr.  Carsten  Schwarz 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Charité Universitätsmedizin BerlinKlinik für Pädiatrie m.S. Pneumologie und Immunologie Christiane Herzog Zentrum Berlin
    • Mr.  Dr.  Carsten  Schwarz 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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Sources of Monetary or Material Support

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    • Gilead Sciences GmbH
    • Ms.  Nike  Hucke 
    • Fraunhoferstraße 17
    • 82152  München
    • 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.