AsthmaNCT01898767
Eicosanoid Lipids by Airway Cells During Infection With Human Rhinoviruses
An observational study of Asthma, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The long-range goal of this protocol is to more completely understand the risks and the pathophysiology of asthma exacerbations, in order to develop prevention strategies and/or expedite a return to complete control of baseline asthma symptoms. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Asthma
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Dec 2013to 29 Aug 2017
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Study population: Subjects with mild asthma from Madison, WI region
Who may be able to join
- Age 18-55 years
- Diagnosis of mild asthma
- Pre-albuterol forced expiratory volume in the first second (FEV1) of >70% predicted.
- Confirmation of asthma diagnosis by either an improvement in FEV1 after four puffs of albuterol by ≥ 12%, or a decline in FEV1 by ≥ 20% after a graded challenge with inhaled methacholine with a provocative concentration causing a 20% fall ≤ 8 mg/mL
- Documented negative Tuberculin skin test (PPD) within the last 12 months or a medical history that is consistent with a low probability of exposure to tuberculosis (i.e. the subject is not a health worker, has not traveled to endemic areas, and has no pre-existing medical or social risk factors for tuberculosis).
- Safety laboratory assessments within normal ranges (labs to include complete blood count with differential and platelet count, PT/INR, creatinine, ALT)
- Women of child-bearing potential (WCBP) must have a negative urine pregnancy test (urine HCG) within 48 hours of the methacholine challenge at Visit 2, within 48 hours of the bronchoscopy at Visit 3 and within 48 hrs of Visit 4. WCBP must agree to use a reliable method of birth control for the duration of the study (reliable methods of birth control can include abstinence, barrier methods, oral contraceptives, injection contraceptives or skin absorption contraceptives).
- In the opinion of the investigator, capable and willing to grant written informed consent and cooperate with study procedures and requirements.
Who cannot join
- Major health problems such as autoimmune disease, heart disease, type I and II diabetes, uncontrolled hypertension or lung diseases other than asthma. The listed health problems are definitive exclusion but decisions regarding major health problems not listed will be based upon the judgment of the investigator.
- No pre-existing chronic infectious disease.
- Any condition for which, in the opinion of the investigator, transient oxyhemoglobin desaturation is inadvisable.
- Pregnant or lactating females or has a planned pregnancy during the course of the study.
- Asthma maintenance therapy other than inhaled short acting beta-agonists within 1 month of screening. This includes but is not limited to inhaled or oral corticosteroids, long acting beta-agonists and leukotriene receptor antagonists.
- Upper or lower respiratory infection within 1 month of screening.
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- Unstable asthma as indicated by self-report of increased symptoms or increased beta-agonist use over the 2 weeks preceding the screening visit.
- Current smokers (defined as smoked within the last year) or a former smoker with a history of >10 pack years.
- Morbid obesity as defined by a Body Mass Index (BMI) > 40.
- Use of an investigational drug within 30 days of entering the study
- History of noncompliance with medical regiments or subjects who are considered unreliable including those with a psychiatric history that, in the opinion of the investigator, may interfere with the conduct of study procedures.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Production of Eicosanoid Lipids by Airway Cells During Infection With Human Rhinoviruses: An In Vitro Model System to Study the Mechanisms of Asthma Exacerbation Resolution
The long-range goal of this protocol is to more completely understand the risks and the pathophysiology of asthma exacerbations, in order to develop prevention strategies and/or expedite a return to complete control of baseline asthma symptoms.
Read the detailed description
Theinvestigators and others have shown that airway epithelial cell infection with human rhinovirus (HRV) is a major risk factor for subsequent exacerbation. Additionally, the investigators have shown that the nucleotide receptor, P2X7, is an important host factor in the prevention of exacerbations, and have data to suggest that this may occur at the level of the alveolar macrophage. Alveolar macrophages facilitate the resolution of inflammation in part by generating eicosanoid metabolites of arachidonic acid including prostaglandin E2 (PGE2) and lipoxin A4 (LXA4). Patients with severe asthma have a reduced capacity to generate PGE2 and LXA4 when compared to those with non-severe asthma, despite alveolar macrophage expression of two of the key enzymes involved in their production. These and other data suggest that pro-resolving eicosanoid metabolism is most efficient when airway epithelial cells are in communication with alveolar macrophages, and that these pathways may be defective in patients with severe asthma. Moreover, inoculation experiments with human rhinovirus (HRV) demonstrate that alveolar macrophages express cox-2 during resolution. These and other data have led to the central hypothesis that transcellular generation of PGE2 and lipoxins is regulated by P2X7-induced cox-2 expression in alveolar macrophages, and that this process facilitates resolution of an HRV-triggered exacerbation.
- Conditions
- Asthma
- Keywords
- mild, asthma, allergic
- Medical subject headings
- Asthma, Lymphoma, Follicular
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 |
|---|---|---|
| Mild asthma | Diagnosis of mild asthma as defined by pre-albuterol forced expiratory volume in the first second (FEV1) of >70% predicted. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cox2 expression
P2X7 agonist-induced fold stimulation (over the media control) of cox2 expression (assessed by densitometry) in alveolar macrophages primed with conditioned medium from minor group HRV-infected epithelial cells.
Measured: One day
BzATP-induced PGE2
The amount of BzATP-induced PGE2 in the culture supernatants of alveolar macrophages primed with HRV-infected epithelial conditioned media
Measured: One day
LXA4 produced by BzATP
The amount of LXA4 produced by BzATP co-treatment of HRV infected of epithelial-macrophage co-cultures.
Measured: One day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2013 (estimated)
- Study start17 Dec 2013
- Primary completion29 Aug 2017
- Study completion29 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Loren Denlinger, MD/PhD, Principal investigator, UW Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01898767
- Sponsor's protocol ID
- 2013-0935
- Other IDs
- 1R01HL115118-01A1
- Status last verified
- Mar 2019
- First submitted
- 9 Jul 2013
- Last updated
- 28 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Production of Eicosanoid Lipids by Airway Cells During Infection With Human Rhinoviruses: An In Vitro Model System to Study the Mechanisms of Asthma Exacerbation Resolution
- ClinicalTrials.gov ID
- NCT01898767
- Acronym / sponsor ID
- 2013-0935
- Conditions
- Asthma
- Keywords
- mild, asthma, allergic
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 17 Dec 2013 (actual)
- Primary completion
- 29 Aug 2017 (actual)
- Study completion
- 29 Aug 2017 (actual)
- First posted
- 12 Jul 2013 (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.
The long-range goal of this protocol is to more completely understand the risks and the pathophysiology of asthma exacerbations, in order to develop prevention strategies and/or expedite a return to complete control of baseline asthma symptoms.
Detailed description
Theinvestigators and others have shown that airway epithelial cell infection with human rhinovirus (HRV) is a major risk factor for subsequent exacerbation. Additionally, the investigators have shown that the nucleotide receptor, P2X7, is an important host factor in the prevention of exacerbations, and have data to suggest that this may occur at the level of the alveolar macrophage. Alveolar macrophages facilitate the resolution of inflammation in part by generating eicosanoid metabolites of arachidonic acid including prostaglandin E2 (PGE2) and lipoxin A4 (LXA4). Patients with severe asthma have a reduced capacity to generate PGE2 and LXA4 when compared to those with non-severe asthma, despite alveolar macrophage expression of two of the key enzymes involved in their production. These and other data suggest that pro-resolving eicosanoid metabolism is most efficient when airway epithelial cells are in communication with alveolar macrophages, and that these pathways may be defective in patients with severe asthma. Moreover, inoculation experiments with human rhinovirus (HRV) demonstrate that alveolar macrophages express cox-2 during resolution. These and other data have led to the central hypothesis that transcellular generation of PGE2 and lipoxins is regulated by P2X7-induced cox-2 expression in alveolar macrophages, and that this process facilitates resolution of an HRV-triggered exacerbation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mild asthma | – | –Diagnosis of mild asthma as defined by pre-albuterol forced expiratory volume in the first second (FEV1) of >70% predicted. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Subjects with mild asthma from Madison, WI region
Key inclusion criteria (8 listed)
- Age 18-55 years
- Diagnosis of mild asthma
- Pre-albuterol forced expiratory volume in the first second (FEV1) of >70% predicted.
- Confirmation of asthma diagnosis by either an improvement in FEV1 after four puffs of albuterol by ≥ 12%, or a decline in FEV1 by ≥ 20% after a graded challenge with inhaled methacholine with a provocative concentration causing a 20% fall ≤ 8 mg/mL
- Documented negative Tuberculin skin test (PPD) within the last 12 months or a medical history that is consistent with a low probability of exposure to tuberculosis (i.e. the subject is not a health worker, has not traveled to endemic areas, and has no pre-existing medical or social risk factors for tuberculosis).
Key exclusion criteria (11 listed)
- Major health problems such as autoimmune disease, heart disease, type I and II diabetes, uncontrolled hypertension or lung diseases other than asthma. The listed health problems are definitive exclusion but decisions regarding major health problems not listed will be based upon the judgment of the investigator.
- No pre-existing chronic infectious disease.
- Any condition for which, in the opinion of the investigator, transient oxyhemoglobin desaturation is inadvisable.
- Pregnant or lactating females or has a planned pregnancy during the course of the study.
- Asthma maintenance therapy other than inhaled short acting beta-agonists within 1 month of screening. This includes but is not limited to inhaled or oral corticosteroids, long acting beta-agonists and leukotriene receptor antagonists.
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
Cox2 expression
Time frame: One day
P2X7 agonist-induced fold stimulation (over the media control) of cox2 expression (assessed by densitometry) in alveolar macrophages primed with conditioned medium from minor group HRV-infected epithelial cells.
BzATP-induced PGE2
Time frame: One day
The amount of BzATP-induced PGE2 in the culture supernatants of alveolar macrophages primed with HRV-infected epithelial conditioned media
LXA4 produced by BzATP
Time frame: One day
The amount of LXA4 produced by BzATP co-treatment of HRV infected of epithelial-macrophage co-cultures.
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 28 Mar 2019.
- Individual participant dataSharing planned: Yes
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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.
Loren Denlinger, MD/PhD principal investigator
UW Madison
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 Asthma, run by University of Wisconsin, Madison 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 8 inclusion and 11 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 28 Mar 2019. 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?
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?
Cox2 expression (time frame: One day). The study lists 3 primary outcomes in all. 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 28 Mar 2019.