Cystic Fibrosis,ABPANCT00906568
Evaluation of Bronchial Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA)
An observational study of Cystic Fibrosis,, run by Johann Wolfgang Goethe University Hospital at 1 site in Germany.
Trial summary
Chronic bronchial inflammation is an important clinical feature in cystic fibrosis. Approximately 10% of patients with cystic fibrosis suffer from Allergic Bronchopulmonary Aspergillosis. In addition airway inflammation in patients with cystic fibrosis (CF) plays a major role in progression of CF lung disease. Read more about this study
- Who is it for?
- Ages 4 to 45 years
- Conditions the study is for
- Cystic Fibrosis,
- How many people
- 40 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2009to Aug 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Outpatients of Department of cystic fibrosis, Goethe University, Frankfurt, Germany
Who may be able to join
- informed consent
- age between 4 and 45 years
- well-known Cystic fibrosis
- Lung function: FEV1 (% pred.) ≥ 70%
Who cannot join
- age < 4 and > 45 years
- lung function: FEV1 (% pred.)< 70%
- other chronic diseases or infections (e.g., HIV, tuberculosis, malignancy)
- pregnancy
- known alcohol, drug and/or drug abuse
- inability to capture the scale and scope of the study
- participation in another study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Presentation and Bronchial Inflammation of Allergic Bronchopulmonary Aspergillosis (ABPA) in Patients With Cystic Fibrosis
Chronic bronchial inflammation is an important clinical feature in cystic fibrosis. Approximately 10% of patients with cystic fibrosis suffer from Allergic Bronchopulmonary Aspergillosis. In addition airway inflammation in patients with cystic fibrosis (CF) plays a major role in progression of CF lung disease. In patients with mild disease (Vital capacity >75%) airway inflammation is often under diagnosed.
Severity of allergy against Aspergillus fumigatus will be examined using radioallergosorbent test and skin Prick-test. Subsequently, in patients with established sensitization (RAST ≥ 0.35 IU/mL) a specific bronchial provocation with Aspergillus will be performed. In addition, exhaled nitric oxide,carbon monoxide, exhaled air temperature and inflammatory cells in sputum is measured. 24 hours after bronchial allergen provocation, exhaled NO, CO, air temperature, and bronchial responsiveness is determined and a second sputum obtained.
This study is designed to characterize patients with CF and sensitization against Aspergillus fumigatus in an early stage to prevent pulmonary complications of ABPA. In addition sputum cytokine profiles in CF patients with mild and moderate disease may be different in patients without and with involvement of small airway disease (SAD).
Read the detailed description
Since symptoms of Bronchopulmonary Aspergillosis are often identical to bacterial infections, the diagnosis is difficult to make. The disease presents with wheezing, pulmonary infiltrates, and bronchiectasis. The most important diagnostic parameters are asthmatic symptoms with obstruction, positive prick test, elevated total IgE, specific IgE and IgG to Aspergillus fumigatus, eosinophilia and radiological findings. Aspergillus fumigatus acts as an allergen Ig-E mediated allergy. Pathophysiological it is assumed that there are two different mechanisms of allergic inflammation. First, there is a direct effect of Aspergillus fumigatus proteases in the alveolar and bronchial epithelium with release of proinflammatory cytokines (IL-8, IL6, MCP-1) and consecutive chemotaxis of inflammatory cells. Second a CD4+ Th2 response with release of IL-4, IL-5 and IL-13. Recently published studies suggest that Aspergillus spores cause the TH2-dependent inflammation directly. So-called Chitinases (part of innate immunity) induce massive IL-13 stimulation. Induction of chitinase activity (CHIT1) leads to an increased remodeling of the lung. It is currently unclear, to which extent Aspergillus-triggered bronchial inflammation in patients with CF is relevant.
- Conditions
- Cystic Fibrosis,
- Keywords
- Cystic fibrosis, Sensitization to Aspergillus, Bronchial allergen challenge, Induced Sputum, Bronchial inflammation, Small airways disease (SAD)
- Medical subject headings
- Cystic Fibrosis, Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Sensitized vs non-sensitized | CF with and without SAD defined by MEF25 <50% |
What is being measured
The primary outcome is the main question the study is designed to answer.
The characterization of patients with CF and sensitization to Aspergillus fumigatus, and analyzing involvement of small airway disease (SAD)
Measured: 1 year
Secondary outcomes (1)
Aspergillus-induced inflammation in sputum using new mediators (IL-8, IL-13, TLR2 and TLR4, LBP and Chitinasen) with the quantitative PCR and protein assay analysis.
In addition planned data analyze: CF-patients will be divided according to their involvement of small airway disease (SAD) into 2 groups: Group 1 without SAD with MEF25 > 50%, Group 2 with SAD with MEF25 < 50% and cell counts and pro-inflammatory cytokines (IL-5, IL-6, IL-8, IL-13, IL-17, INF) measured by quantitative RT-PCR and protein assay will be analyzed.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2009 (estimated)
- Study startApr 2009
- Primary completionMay 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Cystic Fibrosis,Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johann Wolfgang Goethe University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Stefan Zielen, MD, Principal investigator, Goethe-University Frankfurt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00906568
- Sponsor's protocol ID
- KGU-32/09
- Acronym
- ABPA
- Status last verified
- Oct 2010
- First submitted
- 20 May 2009
- Last updated
- 16 Feb 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
de Oliveira E, Giavina-Bianchi P, Fonseca LA, Franca AT, Kalil J. Allergic bronchopulmonary aspergillosis' diagnosis remains a challenge. Respir Med. 2007 Nov;101(11):2352-7. doi: 10.1016/j.rmed.2007.06.018. Epub 2007 Aug 3.
PubMed 17689062Knutsen AP, Bellone C, Kauffman H. Immunopathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis. J Cyst Fibros. 2002 Jun;1(2):76-89. doi: 10.1016/s1569-1993(02)00033-4.
PubMed 15463812Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, Denning DW, Crameri R, Brody AS, Light M, Skov M, Maish W, Mastella G; Participants in the Cystic Fibrosis Foundation Consensus Conference. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003 Oct 1;37 Suppl 3:S225-64. doi: 10.1086/376525.
PubMed 12975753Almeida MB, Bussamra MH, Rodrigues JC. ABPA diagnosis in cystic fibrosis patients: the clinical utility of IgE specific to recombinant Aspergillus fumigatus allergens. J Pediatr (Rio J). 2006 May-Jun;82(3):215-20. doi: 10.2223/JPED.1479. Epub 2006 May 26.
PubMed 16738737Skov M, Pressler T, Jensen HE, Hoiby N, Koch C. Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA). Thorax. 1999 Jan;54(1):44-50. doi: 10.1136/thx.54.1.44.
PubMed 10343631D'Amato G. Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial asthma and allergic respiratory diseases. Eur J Pharmacol. 2006 Mar 8;533(1-3):302-7. doi: 10.1016/j.ejphar.2005.12.045. Epub 2006 Feb 7.
PubMed 16464445Kauffman HF. Immunopathogenesis of allergic bronchopulmonary aspergillosis and airway remodeling. Front Biosci. 2003 Jan 1;8:e190-6. doi: 10.2741/990.
PubMed 12456379Mall MA, Harkema JR, Trojanek JB, Treis D, Livraghi A, Schubert S, Zhou Z, Kreda SM, Tilley SL, Hudson EJ, O'Neal WK, Boucher RC. Development of chronic bronchitis and emphysema in beta-epithelial Na+ channel-overexpressing mice. Am J Respir Crit Care Med. 2008 Apr 1;177(7):730-42. doi: 10.1164/rccm.200708-1233OC. Epub 2007 Dec 13.
PubMed 18079494Reese TA, Liang HE, Tager AM, Luster AD, Van Rooijen N, Voehringer D, Locksley RM. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature. 2007 May 3;447(7140):92-6. doi: 10.1038/nature05746. Epub 2007 Apr 22.
PubMed 17450126Seibold MA, Donnelly S, Solon M, Innes A, Woodruff PG, Boot RG, Burchard EG, Fahy JV. Chitotriosidase is the primary active chitinase in the human lung and is modulated by genotype and smoking habit. J Allergy Clin Immunol. 2008 Nov;122(5):944-950.e3. doi: 10.1016/j.jaci.2008.08.023. Epub 2008 Oct 9.
PubMed 18845328Zhu Z, Zheng T, Homer RJ, Kim YK, Chen NY, Cohn L, Hamid Q, Elias JA. Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation. Science. 2004 Jun 11;304(5677):1678-82. doi: 10.1126/science.1095336.
PubMed 15192232
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Presentation and Bronchial Inflammation of Allergic Bronchopulmonary Aspergillosis (ABPA) in Patients With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT00906568
- Acronym / sponsor ID
- ABPA / KGU-32/09
- Conditions
- Cystic Fibrosis,
- Keywords
- Cystic fibrosis, Sensitization to Aspergillus, Bronchial allergen challenge, Induced Sputum, Bronchial inflammation, Small airways disease (SAD)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Johann Wolfgang Goethe University HospitalUniversity, hospital or other
- Study start
- Apr 2009
- Primary completion
- May 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 21 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic bronchial inflammation is an important clinical feature in cystic fibrosis. Approximately 10% of patients with cystic fibrosis suffer from Allergic Bronchopulmonary Aspergillosis. In addition airway inflammation in patients with cystic fibrosis (CF) plays a major role in progression of CF lung disease. In patients with mild disease (Vital capacity >75%) airway inflammation is often under diagnosed.
Severity of allergy against Aspergillus fumigatus will be examined using radioallergosorbent test and skin Prick-test. Subsequently, in patients with established sensitization (RAST ≥ 0.35 IU/mL) a specific bronchial provocation with Aspergillus will be performed. In addition, exhaled nitric oxide,carbon monoxide, exhaled air temperature and inflammatory cells in sputum is measured. 24 hours after bronchial allergen provocation, exhaled NO, CO, air temperature, and bronchial responsiveness is determined and a second sputum obtained.
This study is designed to characterize patients with CF and sensitization against Aspergillus fumigatus in an early stage to prevent pulmonary complications of ABPA. In addition sputum cytokine profiles in CF patients with mild and moderate disease may be different in patients without and with involvement of small airway disease (SAD).
Detailed description
Since symptoms of Bronchopulmonary Aspergillosis are often identical to bacterial infections, the diagnosis is difficult to make. The disease presents with wheezing, pulmonary infiltrates, and bronchiectasis. The most important diagnostic parameters are asthmatic symptoms with obstruction, positive prick test, elevated total IgE, specific IgE and IgG to Aspergillus fumigatus, eosinophilia and radiological findings. Aspergillus fumigatus acts as an allergen Ig-E mediated allergy. Pathophysiological it is assumed that there are two different mechanisms of allergic inflammation. First, there is a direct effect of Aspergillus fumigatus proteases in the alveolar and bronchial epithelium with release of proinflammatory cytokines (IL-8, IL6, MCP-1) and consecutive chemotaxis of inflammatory cells. Second a CD4+ Th2 response with release of IL-4, IL-5 and IL-13. Recently published studies suggest that Aspergillus spores cause the TH2-dependent inflammation directly. So-called Chitinases (part of innate immunity) induce massive IL-13 stimulation. Induction of chitinase activity (CHIT1) leads to an increased remodeling of the lung. It is currently unclear, to which extent Aspergillus-triggered bronchial inflammation in patients with CF is relevant.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sensitized vs non-sensitized | – | –CF with and without SAD defined by MEF25 <50% |
Who may qualify
- Ages
- 4 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Outpatients of Department of cystic fibrosis, Goethe University, Frankfurt, Germany
Key inclusion criteria (4 listed)
- informed consent
- age between 4 and 45 years
- well-known Cystic fibrosis
- Lung function: FEV1 (% pred.) ≥ 70%
Key exclusion criteria (7 listed)
- age < 4 and > 45 years
- lung function: FEV1 (% pred.)< 70%
- other chronic diseases or infections (e.g., HIV, tuberculosis, malignancy)
- pregnancy
- known alcohol, drug and/or drug abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The characterization of patients with CF and sensitization to Aspergillus fumigatus, and analyzing involvement of small airway disease (SAD)
Time frame: 1 year
1 secondary outcome
Aspergillus-induced inflammation in sputum using new mediators (IL-8, IL-13, TLR2 and TLR4, LBP and Chitinasen) with the quantitative PCR and protein assay analysis.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2011.
- Background: PubMed 17689062de Oliveira E, Giavina-Bianchi P, Fonseca LA, Franca AT, Kalil J. Allergic bronchopulmonary aspergillosis' diagnosis remains a challenge. Respir Med. 2007 Nov;101(11):2352-7. doi: 10.1016/j.rmed.2007.06.018. Epub 2007 Aug 3.
- Background: PubMed 15463812Knutsen AP, Bellone C, Kauffman H. Immunopathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis. J Cyst Fibros. 2002 Jun;1(2):76-89. doi: 10.1016/s1569-1993(02)00033-4.
- Background: PubMed 12975753Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, Denning DW, Crameri R, Brody AS, Light M, Skov M, Maish W, Mastella G; Participants in the Cystic Fibrosis Foundation Consensus Conference. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003 Oct 1;37 Suppl 3:S225-64. doi: 10.1086/376525.
- Background: PubMed 16738737Almeida MB, Bussamra MH, Rodrigues JC. ABPA diagnosis in cystic fibrosis patients: the clinical utility of IgE specific to recombinant Aspergillus fumigatus allergens. J Pediatr (Rio J). 2006 May-Jun;82(3):215-20. doi: 10.2223/JPED.1479. Epub 2006 May 26.
- Background: PubMed 10343631Skov M, Pressler T, Jensen HE, Hoiby N, Koch C. Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA). Thorax. 1999 Jan;54(1):44-50. doi: 10.1136/thx.54.1.44.
- Background: PubMed 16464445D'Amato G. Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial asthma and allergic respiratory diseases. Eur J Pharmacol. 2006 Mar 8;533(1-3):302-7. doi: 10.1016/j.ejphar.2005.12.045. Epub 2006 Feb 7.
- Background: PubMed 12456379Kauffman HF. Immunopathogenesis of allergic bronchopulmonary aspergillosis and airway remodeling. Front Biosci. 2003 Jan 1;8:e190-6. doi: 10.2741/990.
- Background: PubMed 18079494Mall MA, Harkema JR, Trojanek JB, Treis D, Livraghi A, Schubert S, Zhou Z, Kreda SM, Tilley SL, Hudson EJ, O'Neal WK, Boucher RC. Development of chronic bronchitis and emphysema in beta-epithelial Na+ channel-overexpressing mice. Am J Respir Crit Care Med. 2008 Apr 1;177(7):730-42. doi: 10.1164/rccm.200708-1233OC. Epub 2007 Dec 13.
- Background: PubMed 17450126Reese TA, Liang HE, Tager AM, Luster AD, Van Rooijen N, Voehringer D, Locksley RM. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature. 2007 May 3;447(7140):92-6. doi: 10.1038/nature05746. Epub 2007 Apr 22.
- Background: PubMed 18845328Seibold MA, Donnelly S, Solon M, Innes A, Woodruff PG, Boot RG, Burchard EG, Fahy JV. Chitotriosidase is the primary active chitinase in the human lung and is modulated by genotype and smoking habit. J Allergy Clin Immunol. 2008 Nov;122(5):944-950.e3. doi: 10.1016/j.jaci.2008.08.023. Epub 2008 Oct 9.
- Background: PubMed 15192232Zhu Z, Zheng T, Homer RJ, Kim YK, Chen NY, Cohn L, Hamid Q, Elias JA. Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation. Science. 2004 Jun 11;304(5677):1678-82. doi: 10.1126/science.1095336.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan Zielen, MD principal investigator
Goethe-University Frankfurt
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis,, run by Johann Wolfgang Goethe University Hospital at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The characterization of patients with CF and sensitization to Aspergillus fumigatus, and analyzing involvement of small airway disease (SAD) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00906568, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2011.