Aspirin Exacerbated Respiratory DiseaseAERDNCT04261582
Genetics and Genomics of Aspirin Exacerbated Respiratory Disease (AERD)
An observational study of Aspirin Exacerbated Respiratory Disease and Aspirin-Sensitive Asthma, run by National Jewish Health at 1 site in United States.
Trial summary
Aspirin Exacerbated Respiratory Disease (AERD) is a relatively homogeneous disease characterized by adult-onset severe asthma, development of non-cancerous growths in the nasal canal (i.e. nasal polyps) and aspirin allergy. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Aspirin Exacerbated Respiratory Disease, Aspirin-Sensitive Asthma, Nasal Polyps
- How many people
- 245 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Nov 2018to Apr 2022
- 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 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: AERD participants, a subtype of severe asthma characterized by inflammation of the nasal cavity, development of non-cancerous growths, and an allergy to aspirin; 35 healthy control participants. Populations will be recruited from clinic visits or clinical research inquiries, all volunteers.
Who may be able to join
- Physician diagnosis of asthma
- Physician diagnosis of chronic nasal disease featuring nasal polyps
- Sensitivity to aspirin verified by an aspirin provocative challenge in clinic
- Healthy control participant
Who cannot join
- Active smoking
- Pregnancy
- History of greater than or equal to 10 pack-years of smoking
- Any significant comorbid conditions that could inadvertently interfere with study results
- Conditions that require bursts of oral corticosteroids
- Other significant lung diseases
- Other disease in the view of the investigator prohibits participation in the study
Trial locations and contacts
1 site in 1 country.
About this study
Aspirin Exacerbated Respiratory Disease (AERD) is a relatively homogeneous disease characterized by adult-onset severe asthma, development of non-cancerous growths in the nasal canal (i.e. nasal polyps) and aspirin allergy. The cause of AERD is unknown, although likely results from environmental insults in combination with genetic susceptibility. AERD disease homogeneity increases the possibility of discovering narrowly-defined genetic contributors, and makes it an ideal population to study the genetic and epigenetic changes that cause asthma. Researchers recently discovered that gene expression of epithelial growth and repair (EGR) genes are substantially decreased in bronchial airway epithelial cells of severe asthmatics compared to less severe asthmatics and healthy controls. This new finding indicates that epithelial integrity and related processes may be of primary importance to the development of severe asthma, and potentially the severe asthma subtype, AERD. This finding was later supported in a subsequent lab model, which showed that blocking a central epithelial repair and differentiation gene, human epidermal growth factor receptor 2 (ERBB2), decreased healing time of bronchial epithelial cells after injury. Thus, the objective of the proposed study is to determine whether EGR gene are also down-regulated in AERD, a homogeneous severe asthma subtype. As an extension, the researchers will also determine whether genetic mutations and/or epigenetic changes relate to and potentially explain this down-regulation of EGR genes. Specifically, the researchers plan to obtain gene expression of freshly brushed nasal airway epithelial cells of 140 AERD patients, 70 non-aspirin sensitive asthma patients, and 35 healthy controls, noting that nasal epithelial gene expression has recently been shown to mirror lung epithelial changes in asthmatic airways. Swabbing the nasal canal for epithelial cells allows to evaluate airway epithelial cell gene expression non-invasively. Our experimental design contrasts AERD gene expression profiles against healthy controls, and determines whether EGR genes are depressed in AERD relative to health controls. As a corollary, the researchers look to discover an AERD-specific gene expression profile which may one-day aid in diagnosis and expand current knowledge of disease mechanisms. As an extension, the researchers will correlate gene expression changes, specifically any finding of down-regulated EGR genes, with methylation changes (i.e. epigenetic changes) and genetic mutations.
- Medical subject headings
- Nasal Polyps
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 |
|---|---|---|
| AERD participants | Participants with aspirin exacerbated respiratory disease. Adults with aspirin allergy, nasal polyps and adult-onset severe asthma. | |
| Healthy controls | Healthy participants that do not have asthma. | |
| Non-aspirin sensitive asthma participants | Participants with asthma, but that do not have a sensitivity to aspirin. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of EGR related gene expression in AERD
Researchers will obtain global gene expression of freshly brushed nasal airway epithelial cells of AERD patients, non-aspirin sensitive asthma patients, and healthy patients using nasal swab samples and running RNAseq on the collected cells. Researchers will contrast AERD gene profiles against non-aspirin sensitive asthma patients and healthy patients and determine whether down-regulation of EGR genes is found in AERD.
Measured: Through study completion, 3 years
Secondary outcomes (2)
Relation of EGR gene expression to epigenetic gene methylation
To determine whether whole genome methylation profiling is altered in association with down-regulated EGR genes. Researchers will obtain complementary whole-genome methylation profiles of the study participants and will evaluate whether down-regulated EGR genes in AERD patients are associated with methylation differences by a composite analysis integrating expression and epigenetic data. MethylMix R software program will be used to identify methylation changes associated with gene expression changes. MethylMix integrates DNA methylation from normal and disease samples with matched gene expression. In summary, MethylMix defines hyper and hypomethylated genes by comparing methylation values of disease tissue vs. normal.
Measured: Through study completion, 3 years
Influence of Genetic variation on EGR related gene expression
To determine whether genetic mutations associate with down-regulated EGR gene expression in AERD patients. We will obtain genotypes on these same study participants and evaluate whether down-regulated EGR genes are associated with mutations by a composite analysis integrating expression and genotypes. The Affymetrix genotyping workflow consists of 4 steps; first 3 steps use a set of stand-alone software packages, and the 4th step using R package SNPolisher. Sample QC will be evaluated by Dish-QC statistic, retaining samples with default Dish-QC > 82%. Genotyped samples with a call rate lower than default value of 97% will be excluded. Platewise QC will be evaluated by manually calculating 'Plate Pass Rate' and 'Average Plate Call Rate' statistics, with default cutoff values of 95 and 99%. Genotyping step will be rerun for samples passing quality criteria. SNPolisher will evaluate quality of the signal and classify each SNP probe.
Measured: Through study completion, 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2020
- Study start6 Nov 2018
- Primary completionApr 2022 (estimated)
- Study completionApr 2022 (estimated)
Why it stopped: On hold due to COVID-19 outbreak
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aspirin Exacerbated Respiratory DiseaseStudies 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
- Prospective
- Enrolment
- 245 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Jewish Health
- Sponsor type
- University, hospital or other
- Collaborators
- The Scripps Research Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04261582
- Sponsor's protocol ID
- HS-3200sIRB
- Acronym
- AERD
- Status last verified
- Aug 2021
- First submitted
- 5 Dec 2019
- Last updated
- 1 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetics and Genomics of Aspirin Exacerbated Respiratory Disease (AERD)
- ClinicalTrials.gov ID
- NCT04261582
- Acronym / sponsor ID
- AERD / HS-3200sIRB
- Study type
- Observational
- Recruitment status
- SuspendedReason stopped: On hold due to COVID-19 outbreak
- Enrolment
- 245 participants (estimated)
- Lead sponsor
- National Jewish HealthUniversity, hospital or other
- Collaborators
- The Scripps Research Institute
- Study start
- 6 Nov 2018 (actual)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 10 Feb 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.
Aspirin Exacerbated Respiratory Disease (AERD) is a relatively homogeneous disease characterized by adult-onset severe asthma, development of non-cancerous growths in the nasal canal (i.e. nasal polyps) and aspirin allergy. The cause of AERD is unknown, although likely results from environmental insults in combination with genetic susceptibility. AERD disease homogeneity increases the possibility of discovering narrowly-defined genetic contributors, and makes it an ideal population to study the genetic and epigenetic changes that cause asthma. Researchers recently discovered that gene expression of epithelial growth and repair (EGR) genes are substantially decreased in bronchial airway epithelial cells of severe asthmatics compared to less severe asthmatics and healthy controls. This new finding indicates that epithelial integrity and related processes may be of primary importance to the development of severe asthma, and potentially the severe asthma subtype, AERD. This finding was later supported in a subsequent lab model, which showed that blocking a central epithelial repair and differentiation gene, human epidermal growth factor receptor 2 (ERBB2), decreased healing time of bronchial epithelial cells after injury. Thus, the objective of the proposed study is to determine whether EGR gene are also down-regulated in AERD, a homogeneous severe asthma subtype. As an extension, the researchers will also determine whether genetic mutations and/or epigenetic changes relate to and potentially explain this down-regulation of EGR genes. Specifically, the researchers plan to obtain gene expression of freshly brushed nasal airway epithelial cells of 140 AERD patients, 70 non-aspirin sensitive asthma patients, and 35 healthy controls, noting that nasal epithelial gene expression has recently been shown to mirror lung epithelial changes in asthmatic airways. Swabbing the nasal canal for epithelial cells allows to evaluate airway epithelial cell gene expression non-invasively. Our experimental design contrasts AERD gene expression profiles against healthy controls, and determines whether EGR genes are depressed in AERD relative to health controls. As a corollary, the researchers look to discover an AERD-specific gene expression profile which may one-day aid in diagnosis and expand current knowledge of disease mechanisms. As an extension, the researchers will correlate gene expression changes, specifically any finding of down-regulated EGR genes, with methylation changes (i.e. epigenetic changes) and genetic mutations.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AERD participants | – | –Participants with aspirin exacerbated respiratory disease. Adults with aspirin allergy, nasal polyps and adult-onset severe asthma. |
| Healthy controls | – | –Healthy participants that do not have asthma. |
| Non-aspirin sensitive asthma participants | – | –Participants with asthma, but that do not have a sensitivity to aspirin. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- AERD participants, a subtype of severe asthma characterized by inflammation of the nasal cavity, development of non-cancerous growths, and an allergy to aspirin; 35 healthy control participants. Populations will be recruited from clinic visits or clinical research inquiries, all volunteers.
Key inclusion criteria (4 listed)
- Physician diagnosis of asthma
- Physician diagnosis of chronic nasal disease featuring nasal polyps
- Sensitivity to aspirin verified by an aspirin provocative challenge in clinic
- Healthy control participant
Key exclusion criteria (7 listed)
- Active smoking
- Pregnancy
- History of greater than or equal to 10 pack-years of smoking
- Any significant comorbid conditions that could inadvertently interfere with study results
- Conditions that require bursts of oral corticosteroids
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
Evaluation of EGR related gene expression in AERD
Time frame: Through study completion, 3 years
Researchers will obtain global gene expression of freshly brushed nasal airway epithelial cells of AERD patients, non-aspirin sensitive asthma patients, and healthy patients using nasal swab samples and running RNAseq on the collected cells. Researchers will contrast AERD gene profiles against non-aspirin sensitive asthma patients and healthy patients and determine whether down-regulation of EGR genes is found in AERD.
2 secondary outcomes
Relation of EGR gene expression to epigenetic gene methylation
Time frame: Through study completion, 3 years
Influence of Genetic variation on EGR related gene expression
Time frame: Through study completion, 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2021.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Aspirin Exacerbated Respiratory Disease and Aspirin-Sensitive Asthma, run by National Jewish Health at 1 site in United States.
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: paused, as of the sponsor's last update on 1 Sep 2021. 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 United States. 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?
Results are not available in the source record.
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?
Evaluation of EGR related gene expression in AERD (time frame: Through study completion, 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 1 Sep 2021.