Aspergillosis PneumoniaNIPANCT04358419
Non-invasive Diagnosis of Invasive Pulmonary Aspergillosis by Use of Biomarkers in Exhaled Breath Condensate
An observational study of Aspergillosis Pneumonia and Pneumocystis Pneumonia, run by Inger Lise Gade at 1 site in Denmark.
Trial summary
In this study, a new, non-invasive method for diagnosis of pulmonary aspergillosis (PA) will be tested in a clinical pilot project. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Aspergillosis Pneumonia, Pneumocystis Pneumonia
- What is being tested?
- Aspergillus specific proteins in exhaled breath condensate (EBC) and Pneumocystis jirovecii DNA in exhaled breath condensate (EBC)
- How many people
- 101 participants
- Where
- 1 siteDenmark
- Study dates
- 17 Apr 2020to 31 Dec 2023
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: In the main study the investigators expect to include * 15 patients with proven/probable/possible Pulmonary Aspergillosis (PA) * 15 patients with suspected, but rejected PA * 15 healty controls In the substudy the investigators expect to include * 4 patients with verified pnemocystis pneumonia * 4 patients suspected but rejected pneumocystis pneumonia * 4 healthy controls
Who may be able to join
- Suspected/confirmed PA patients:
- Hospitalized or ambulatory patients with a suspected PA at Aalborg University Hospital.
- Are conscious and able to understand the given study information.
- Possess legal capacity.
- Age above 18 years.
- Informed, signed consent is obtained.
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- Clinically stable, which is defined as patients with stable blood pressure and not in need for other treatments.
- No need for organ support, which comprises need for vasopressors or inotropes, mechanical ventilation, extra corporal circulation or renal replacement therapy.
- Controls
- Patients as the PA patients, but where the diagnosis of PA is rejected will be included as controls.
- Suspected/confirmed pneumocystis pneumonia patients:
- Hospitalized or ambulatory patients with a suspected pneumocystis pneumonia at Aalborg University Hospital - chest x-ray must support the tentative diagnosis of pneumocystis pneumonia.
- Are conscious and able to understand the given study information.
- Possess legal capacity.
- Age above 18 years.
- Informed, signed consent is obtained.
- Clinically stable, which is defined as patients with stable blood pressure and not in need for other treatments.
- No need for organ support, which comprises need for vasopressors or inotropes, mechanical ventilation, extra corporal circulation or renal replacement therapy.
- Controls
- Patients as the pneumocystis pneumonia patients, but where the diagnosis is rejected.
- Healthy controls for the confirmed PA patients and confirmed pneumocystis pneumonia patients In addition, 19 healthy controls (i.e. patients/subjects who undergo diagnostic work-up for benign or indolent hematological diseases without suspected PA or pneumocystis pneumonia) will be recruited, as described below.
- Healthy controls and patients who are going through diagnostic work-up for indolent hematological cancer types or benign hematological diseases, at the Department of Hematology, Aalborg University Hospital.
- Same gender and age (within a 10-year range) as an included patient with proven/probable/possible PA (15 subjects).
- Same gender and age (within a 10-year range) as an included patient with verified pneumocystis pneumonia (4 subjects).
- Are conscious and able to understand the given study information.
- Possess legal capacity.
- Age above 18 years.
- Informed, signed consent is obtained.
Who cannot join
- PA patients, pneumocystis pneumonia patients and controls:
- No upper age limit will be applied.
Trial locations and contacts
1 site in 1 country.
About this study
In this study, a new, non-invasive method for diagnosis of pulmonary aspergillosis (PA) will be tested in a clinical pilot project.
Read the detailed description
Background:
The search for biomarkers to enhance and improve diagnosis of PA is ongoing, mainly focused on markers detected in the blood and bronchoalveolar lavage (BAL) fluids. In this study, the investigators will investigate whether exhaled breath condensate is a useful source for diagnosis of PA either by existing methods (i.e. polymerase chain reaction (PCR) detection of Aspergillus DNA) or by analysis of the proteome. However, extraction of Aspergillus DNA has never been done in the EBC before. In this pilot study the investigators will investigate whether it is possible to purify DNA from pneumocystis from EBC of patients with proven pneumocystis pneumonia both because the diagnostic test for pneumocystis pneumonia is more sensitive and specific and also due to the fact that pneumocystis pneumonia is more common than PA. The investigators will spare the EBC samples from patients PA for the protein analysis in this study.
No previous studies have investigated the potential of EBC protein analysis as a diagnostic tool in PA infections. In this pilot study, the investigators will test whether Aspergillus proteins are present in the EBC from patients with proven/probable/possible PA.
Methods:
The study will compare the protein profiles of exhaled breath condensate (EBC) collected from patients with proven, probable or possible pulmonary aspergillus (PA) infection and patients with suspected PA infection where routine diagnostic workup ruled out PA, and negative controls, i.e. patients who undergo diagnostic workup for benign/indolent conditions and without suspected PA, with same age (within a range of 10 years) and gender from the outpatient clinic at department of hematology, department of infectious diseases, department of respiratory diseases and department of cardiothoracic surgery at Aalborg University Hospital. The main-outcome, i.e. means of the relative amounts of specific proteins in the EBC samples, will be compared by unpaired t-tests after assessment of normality and standard deviations within the two groups in the following comparisons: proven/probable/possible PA vs. patients where PA was ruled out and proven/probable/possible PA vs. negative controls. In case three groups are compared, the one-way analysis of variance will be applied, but this is not within the main scope of our study.
In a sub-study, the investigators will collect EBC from patients with suspected Pneumocystis jirovecii pneumonia and healthy controls, i.e. patients who undergo diagnostic workup for benign/indolent conditions and without suspected pneumocystis pneumonia. Diagnostic tests for pneumocystis pneumonia are highly specific and sensitive. The investigators will test whether pneumocystis DNA is detectable in the EBC from these patients and learn how DNA should be extracted from the EBC samples. DNA extraction and analysis will be done locally. The investigators will use the experiences and results from this sub-study in the design of further studies of detection of Aspergillus in the EBC after this pilot study, if relevant. The investigators will include four patients with confirmed pneumocystis pneumonia and four healthy controls. Oral washes pneumocystis tests will be collected immediately before the EBC is collected for both cases and healthy controls. If the diagnosis of pneumocystis pneumonia is not confirmed in a patient with suspected pneumocystis pneumonia, the patient will be included as negative control.
Blood samples (i.e. excess plasma/serum from routine blood samples drawn as a part of routine diagnostic work-up) from the study participants (both PA-patients, healthy controls, and pneumocystis pneumonia patients) will be stored for standardization and verification and supplementing analysis of possible findings in the EBC. Plasma is the part of a blood sample that is left after centrifugation when an anticoagulant agent is added upon drawing of the blood sample. Hence, for some of the samples (citrate, ethylenediaminetetraacetic acid (EDTA), heparin coated tubes), the investigators will store plasma (i.e. cell-free part of the blood with coagulation factors) and for the blood sample that was allowed to coagulate in the tube, the stored material will be serum (i.e. cell-free part of the blood without coagulation factors). In order to qualify the most suitable markers and substrates for standardization, the analysis of the EBC samples must be completed before the blood samples can be analyzed. Only biochemical, no genetic analysis will be conducted. For the healthy PA controls, the investigators will ask for an extra blood sample for detection of aspergillus galactomannan. For the healthy pneumocystis pneumonia controls, the investigators will ask for a pneumocystis oral wash for test of pneumocystis.
- Conditions
- Aspergillosis Pneumonia, Pneumocystis Pneumonia
- Being tested
- Aspergillus specific proteins in exhaled breath condensate (EBC), Pneumocystis jirovecii DNA in exhaled breath condensate (EBC)
- Medical subject headings
- Pneumonia, Pneumocystis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aspergillus specific proteins in exhaled breath condensate (EBC)Diagnostic test
The EBC will be collected by use of the RTube(R) system which is commercially available for the purpose of collection of EBC. As the patient breathes through a mouth piece, the exhaled breath is lead through a cooling chamber where the vaporous part of the exhaled breath condenses. The investigators aim at collecting a total minimum of 3.0 mL EBC per study participant in order to have sufficient amount of protein for the subsequent analysis.
Pneumocystis jirovecii DNA in exhaled breath condensate (EBC)Diagnostic test
The EBC will be collected by use of the RTube(R) system which is commercially available for the purpose of collection of EBC. As the patient breathes through a mouth piece, the exhaled breath is lead through a cooling chamber where the vaporous part of the exhaled breath condenses. The investigators aim at collecting a total minimum of 3.0 mL EBC per study participant in order to have sufficient amount of protein for the subsequent analysis.
| Study group | Role | What they receive |
|---|---|---|
| PA proven/probable/possible | 15 patients with proven, probable or possible PA Receives: Diagnostic Test: Aspergillus specific proteins in exhaled breath condensate (EBC) | |
| PA suspected, not confirmed | 15 patients as the PA patients, but where the diagnosis of PA is rejected. Receives: Diagnostic Test: Aspergillus specific proteins in exhaled breath condensate (EBC) | |
| Healthy controls (PA) | 15 subjects of same gender and age as an included patient with proven/probable/possible PA as healthy controls. Receives: Diagnostic Test: Aspergillus specific proteins in exhaled breath condensate (EBC) | |
| Pneumocystis pneumonia positive | Four patients with confirmed pneumocystis pneumonia Receives: Diagnostic Test: Pneumocystis jirovecii DNA in exhaled breath condensate (EBC) | |
| Pneumocystis pneumonia negative | If the diagnosis of pneumocystis pneumonia is not confirmed in a patient with suspected pneumocystis pneumonia, the patient will be included as negative control. Four such patients will be included as healthy controls. Receives: Diagnostic Test: Pneumocystis jirovecii DNA in exhaled breath condensate (EBC) | |
| Healthy controls (pneumocystis pneumonia) | Four subjects of same gender and age as an included patient with verified pneumocystis pneumonia as healthy controls. Receives: Diagnostic Test: Pneumocystis jirovecii DNA in exhaled breath condensate (EBC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of Aspergillus proteins in the EBC from patients with proven/probable/possible PA
The primary outcome is identification of Aspergillus proteins in the EBC from patients with proven/probable/possible PA
Measured: 2-3 years
Secondary outcomes (1)
Detection of Pneumocystis DNA in the EBC
Can Pneumocystis DNA be detected in the EBC (yes/no)
Measured: 1-2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start17 Apr 2020
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aspergillosis PneumoniaStudies 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-control
- Time perspective
- Cross-sectional
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inger Lise Gade
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital
- Responsible party
- Sponsor-investigator, Inger Lise Gade, Aalborg University Hospital
- Investigators
- Inger L Gade, MD PhD, Principal investigator, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04358419
- Sponsor's protocol ID
- ILG-NIPA-2020
- Other IDs
- N-20190070
- Acronym
- NIPA
- Status last verified
- Feb 2024
- First submitted
- 21 Apr 2020
- Last updated
- 13 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Diagnosis of Invasive Pulmonary Aspergillosis by Use of Biomarkers in Exhaled Breath Condensate
- ClinicalTrials.gov ID
- NCT04358419
- Acronym / sponsor ID
- NIPA / ILG-NIPA-2020
- Conditions
- Aspergillosis Pneumonia, Pneumocystis Pneumonia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Inger Lise GadeUniversity, hospital or other
- Collaborators
- Aarhus University Hospital
- Study start
- 17 Apr 2020 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 24 Apr 2020 (actual)
- 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.
In this study, a new, non-invasive method for diagnosis of pulmonary aspergillosis (PA) will be tested in a clinical pilot project.
Detailed description
Background:
The search for biomarkers to enhance and improve diagnosis of PA is ongoing, mainly focused on markers detected in the blood and bronchoalveolar lavage (BAL) fluids. In this study, the investigators will investigate whether exhaled breath condensate is a useful source for diagnosis of PA either by existing methods (i.e. polymerase chain reaction (PCR) detection of Aspergillus DNA) or by analysis of the proteome. However, extraction of Aspergillus DNA has never been done in the EBC before. In this pilot study the investigators will investigate whether it is possible to purify DNA from pneumocystis from EBC of patients with proven pneumocystis pneumonia both because the diagnostic test for pneumocystis pneumonia is more sensitive and specific and also due to the fact that pneumocystis pneumonia is more common than PA. The investigators will spare the EBC samples from patients PA for the protein analysis in this study.
No previous studies have investigated the potential of EBC protein analysis as a diagnostic tool in PA infections. In this pilot study, the investigators will test whether Aspergillus proteins are present in the EBC from patients with proven/probable/possible PA.
Methods:
The study will compare the protein profiles of exhaled breath condensate (EBC) collected from patients with proven, probable or possible pulmonary aspergillus (PA) infection and patients with suspected PA infection where routine diagnostic workup ruled out PA, and negative controls, i.e. patients who undergo diagnostic workup for benign/indolent conditions and without suspected PA, with same age (within a range of 10 years) and gender from the outpatient clinic at department of hematology, department of infectious diseases, department of respiratory diseases and department of cardiothoracic surgery at Aalborg University Hospital. The main-outcome, i.e. means of the relative amounts of specific proteins in the EBC samples, will be compared by unpaired t-tests after assessment of normality and standard deviations within the two groups in the following comparisons: proven/probable/possible PA vs. patients where PA was ruled out and proven/probable/possible PA vs. negative controls. In case three groups are compared, the one-way analysis of variance will be applied, but this is not within the main scope of our study.
In a sub-study, the investigators will collect EBC from patients with suspected Pneumocystis jirovecii pneumonia and healthy controls, i.e. patients who undergo diagnostic workup for benign/indolent conditions and without suspected pneumocystis pneumonia. Diagnostic tests for pneumocystis pneumonia are highly specific and sensitive. The investigators will test whether pneumocystis DNA is detectable in the EBC from these patients and learn how DNA should be extracted from the EBC samples. DNA extraction and analysis will be done locally. The investigators will use the experiences and results from this sub-study in the design of further studies of detection of Aspergillus in the EBC after this pilot study, if relevant. The investigators will include four patients with confirmed pneumocystis pneumonia and four healthy controls. Oral washes pneumocystis tests will be collected immediately before the EBC is collected for both cases and healthy controls. If the diagnosis of pneumocystis pneumonia is not confirmed in a patient with suspected pneumocystis pneumonia, the patient will be included as negative control.
Blood samples (i.e. excess plasma/serum from routine blood samples drawn as a part of routine diagnostic work-up) from the study participants (both PA-patients, healthy controls, and pneumocystis pneumonia patients) will be stored for standardization and verification and supplementing analysis of possible findings in the EBC. Plasma is the part of a blood sample that is left after centrifugation when an anticoagulant agent is added upon drawing of the blood sample. Hence, for some of the samples (citrate, ethylenediaminetetraacetic acid (EDTA), heparin coated tubes), the investigators will store plasma (i.e. cell-free part of the blood with coagulation factors) and for the blood sample that was allowed to coagulate in the tube, the stored material will be serum (i.e. cell-free part of the blood without coagulation factors). In order to qualify the most suitable markers and substrates for standardization, the analysis of the EBC samples must be completed before the blood samples can be analyzed. Only biochemical, no genetic analysis will be conducted. For the healthy PA controls, the investigators will ask for an extra blood sample for detection of aspergillus galactomannan. For the healthy pneumocystis pneumonia controls, the investigators will ask for a pneumocystis oral wash for test of pneumocystis.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| PA proven/probable/possible | – | Diagnostic Test: Aspergillus specific proteins in exhaled breath condensate (EBC)15 patients with proven, probable or possible PA |
| PA suspected, not confirmed | – | Diagnostic Test: Aspergillus specific proteins in exhaled breath condensate (EBC)15 patients as the PA patients, but where the diagnosis of PA is rejected. |
| Healthy controls (PA) | – | Diagnostic Test: Aspergillus specific proteins in exhaled breath condensate (EBC)15 subjects of same gender and age as an included patient with proven/probable/possible PA as healthy controls. |
| Pneumocystis pneumonia positive | – | Diagnostic Test: Pneumocystis jirovecii DNA in exhaled breath condensate (EBC)Four patients with confirmed pneumocystis pneumonia |
| Pneumocystis pneumonia negative | – | Diagnostic Test: Pneumocystis jirovecii DNA in exhaled breath condensate (EBC)If the diagnosis of pneumocystis pneumonia is not confirmed in a patient with suspected pneumocystis pneumonia, the patient will be included as negative control. Four such patients will be included as healthy controls. |
| Healthy controls (pneumocystis pneumonia) | – | Diagnostic Test: Pneumocystis jirovecii DNA in exhaled breath condensate (EBC)Four subjects of same gender and age as an included patient with verified pneumocystis pneumonia as healthy controls. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- In the main study the investigators expect to include * 15 patients with proven/probable/possible Pulmonary Aspergillosis (PA) * 15 patients with suspected, but rejected PA * 15 healty controls In the substudy the investigators expect to include * 4 patients with verified pnemocystis pneumonia * 4 patients suspected but rejected pneumocystis pneumonia * 4 healthy controls
Key inclusion criteria (28 listed)
- Suspected/confirmed PA patients:
- Controls
- Suspected/confirmed pneumocystis pneumonia patients:
- Controls
- Healthy controls for the confirmed PA patients and confirmed pneumocystis pneumonia patients In addition, 19 healthy controls (i.e. patients/subjects who undergo diagnostic work-up for benign or indolent hematological diseases without suspected PA or pneumocystis pneumonia) will be recruited, as described below.
Key exclusion criteria (2 listed)
- PA patients, pneumocystis pneumonia patients and controls:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aspergillus specific proteins in exhaled breath condensate (EBC)The EBC will be collected by use of the RTube(R) system which is commercially available for the purpose of collection of EBC. As the patient breathes through a mouth piece, the exhaled breath is lead through a cooling chamber where the vaporous part of the exhaled breath condenses. The investigators aim at collecting a total minimum of 3.0 mL EBC per study participant in order to have sufficient amount of protein for the subsequent analysis. | Diagnostic test | Healthy controls (PA), PA proven/probable/possible, PA suspected, not confirmed |
| Pneumocystis jirovecii DNA in exhaled breath condensate (EBC)The EBC will be collected by use of the RTube(R) system which is commercially available for the purpose of collection of EBC. As the patient breathes through a mouth piece, the exhaled breath is lead through a cooling chamber where the vaporous part of the exhaled breath condenses. The investigators aim at collecting a total minimum of 3.0 mL EBC per study participant in order to have sufficient amount of protein for the subsequent analysis. | Diagnostic test | Healthy controls (pneumocystis pneumonia), Pneumocystis pneumonia negative, Pneumocystis pneumonia positive |
Primary outcome
Identification of Aspergillus proteins in the EBC from patients with proven/probable/possible PA
Time frame: 2-3 years
The primary outcome is identification of Aspergillus proteins in the EBC from patients with proven/probable/possible PA
1 secondary outcome
Detection of Pneumocystis DNA in the EBC
Time frame: 1-2 years
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 13 Feb 2024.
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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.
Inger L Gade, MD PhD principal investigator
Aalborg University Hospital
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 Aspergillosis Pneumonia and Pneumocystis Pneumonia, run by Inger Lise Gade at 1 site in Denmark.
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 28 inclusion and 2 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 13 Feb 2024. 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 Denmark. 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?
Identification of Aspergillus proteins in the EBC from patients with proven/probable/possible PA (time frame: 2-3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Feb 2024.