AsthmaPhase 1EFADANCT01733485
Electrophilic Fatty Acid Derivatives in Asthma
A Phase 1 study testing Aspirin and Indomethacin in people with Asthma and Electrophilic Fatty Acids, run by Sally E. Wenzel MD at 1 site in United States.
Trial summary
Asthma is an inflammatory disease, which means it causes swelling in the lungs to cause shortness of breath and/or wheezing. There are several asthma medications that help to reduce this problem. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Asthma, Electrophilic Fatty Acids
- What is being tested?
- Aspirin and Indomethacin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Jun 2017
- Phase
- Phase 1
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of mild to moderate asthma
- No evidence of a previous asthma exacerbation in the preceding 6 weeks (defined as increased severity of respiratory symptoms requiring systemic steroids or escalation of therapy; b) asthma control questionnaire (ACQ) score less than 1.
Who cannot join
- Diagnosis of severe asthma, vocal cord dysfunction, cystic fibrosis, COPD, CAD, hypertension, diabetes or renal failure that is not well controlled
- Greater than 10 pack-year history of smoking;
- Stopped smoking less than 1 year prior to study,
- Taking any aspirin or other NSAIDS on the week prior to bronchoscopy,
- Taking omega-3 fatty acid supplements
- If a subject is currently taking an omega-3 fatty acid supplement and is interested in the study, after a 30 day wash out, the participant can be re-screened and evaluated for participation.
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- Taking pioglitazone or rosiglitazone (synthetic thiazolidinedione PPARg ligands);
- other known pulmonary diseases;
- Inability to undergo bronchoscopy,
- Contraindications or allergy to aspirin or indomethacin,
- Asthmatics with known hypersensitivity to aspirin, and
- Steroid (systemic) dependent
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Asthma is an inflammatory disease, which means it causes swelling in the lungs to cause shortness of breath and/or wheezing. There are several asthma medications that help to reduce this problem.
The objective of this research study is to characterize the presence of electrophilic fatty acids in the bronchial airway of subjects with controlled asthma at baseline and after treatment with Aspirin, Indomethacin, or no treatment at all. The presence of electrophilic fatty acids may indicate inflammation. Aspirin and Indomethacin are known to respectively increase and inhibit the formation of electrophilic fatty acids. By gaining a better understanding of how electrophilic fatty acids work and how they respond to different treatment, researchers hope to be able to find better ways to lessen airway inflammation in asthma in the future.
Read the detailed description
Relevant to asthma, the chemical identities and potent anti-inflammatory signaling actions of endogenously-produced Electrophilic Fatty acid OXidation products (EFOXs) have recently been described. Endogenous EFOXs include nitro and alpha and beta-unsaturated ketone derivatives of unsaturated fatty acids that are generated as byproducts of a) fatty acid oxidation and nitration by inflammatory-derived reactive species and b) enzymatic fatty acid oxygenation reactions catalyzed by cyclooxygenase-2 and lipoxygenases. Recent data reveal that multiple salutary post-translational protein modifications are induced by EFOXs. Specifically, the covalent adduction of functionally-significant thiols in signaling proteins occurs, with these reactions modulating critical inflammatory signaling pathways. These signaling proteins include the nuclear lipid receptor PPARg and the redox-sensitive transcription factors NF kappaB and Keap1/Nrf2. This proposed research investigates the concept that the reversible reaction of EFOXs with critical transcription factors results in the regulation of adaptive responses to inflammation.
In this clinical study, bronchoalveolar lavage fluid (BAL) will be obtained from asthmatics treated with COX-2 inhibitors that enhance (aspirin) and inhibit (indomethacin) COX-2 dependent EFOX generation, as well as from those assigned to no intervention. BAL will be obtained from healthy, non-smoking adults with controlled asthma having at least a 12% increase in FEV1 after short-acting bronchodilator treatment or a positive methacholine response (reduction in FEV1 ≥ 20% at or before 16 mg/ml). A total of 30 asthmatic subjects will be randomized (10 per arm) to a) aspirin, b) indomethacin or c) no intervention groups
- Conditions
- Asthma, Electrophilic Fatty Acids
- Being tested
- Aspirin, Indomethacin
- Keywords
- Asthma, Electrophilic Fatty Acids, Inflammation
- Medical subject headings
- Asthma, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
500 mg/8 h for 5 days
IndomethacinDrug
25 mg/8 h for 5 days
| Study group | Role | What they receive |
|---|---|---|
| Aspirin | Active comparator | Not described Receives: Drug: Aspirin |
| Indomethacin | Active comparator | Not described Receives: Drug: Indomethacin |
| Control | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Airway concentration of electrophilic fatty acids
Patients undergo a baseline bronchoscopy, afterwhich they are randomized to 5 days of a)indomethacin, b) aspirin, c) nothing . After treatment, another bronchoscopy is done. Outcomes are determined after each bronchoscopy
Measured: Change in the bronchoalveolar lavage concentration of electrophilic fatty acids from the first to the second bronchoscopy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2012 (estimated)
- Study startOct 2011
- Primary completionSep 2016
- Study completionJun 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.
- 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sally E. Wenzel MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Sally E. Wenzel MD, University of Pittsburgh
- Investigators
- Fernando Holguin, MD MPH, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01733485
- Sponsor's protocol ID
- U10HL098177
- Acronym
- EFADA
- Status last verified
- Jul 2017
- First submitted
- 15 Nov 2012
- Last updated
- 11 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrophilic Fatty Acid Derivatives in Asthma
- ClinicalTrials.gov ID
- NCT01733485
- Acronym / sponsor ID
- EFADA / U10HL098177
- Conditions
- Asthma, Electrophilic Fatty Acids
- Keywords
- Asthma, Electrophilic Fatty Acids, Inflammation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Sally E. Wenzel MDUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Sep 2016 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 27 Nov 2012 (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.
Asthma is an inflammatory disease, which means it causes swelling in the lungs to cause shortness of breath and/or wheezing. There are several asthma medications that help to reduce this problem.
The objective of this research study is to characterize the presence of electrophilic fatty acids in the bronchial airway of subjects with controlled asthma at baseline and after treatment with Aspirin, Indomethacin, or no treatment at all. The presence of electrophilic fatty acids may indicate inflammation. Aspirin and Indomethacin are known to respectively increase and inhibit the formation of electrophilic fatty acids. By gaining a better understanding of how electrophilic fatty acids work and how they respond to different treatment, researchers hope to be able to find better ways to lessen airway inflammation in asthma in the future.
Detailed description
Relevant to asthma, the chemical identities and potent anti-inflammatory signaling actions of endogenously-produced Electrophilic Fatty acid OXidation products (EFOXs) have recently been described. Endogenous EFOXs include nitro and alpha and beta-unsaturated ketone derivatives of unsaturated fatty acids that are generated as byproducts of a) fatty acid oxidation and nitration by inflammatory-derived reactive species and b) enzymatic fatty acid oxygenation reactions catalyzed by cyclooxygenase-2 and lipoxygenases. Recent data reveal that multiple salutary post-translational protein modifications are induced by EFOXs. Specifically, the covalent adduction of functionally-significant thiols in signaling proteins occurs, with these reactions modulating critical inflammatory signaling pathways. These signaling proteins include the nuclear lipid receptor PPARg and the redox-sensitive transcription factors NF kappaB and Keap1/Nrf2. This proposed research investigates the concept that the reversible reaction of EFOXs with critical transcription factors results in the regulation of adaptive responses to inflammation.
In this clinical study, bronchoalveolar lavage fluid (BAL) will be obtained from asthmatics treated with COX-2 inhibitors that enhance (aspirin) and inhibit (indomethacin) COX-2 dependent EFOX generation, as well as from those assigned to no intervention. BAL will be obtained from healthy, non-smoking adults with controlled asthma having at least a 12% increase in FEV1 after short-acting bronchodilator treatment or a positive methacholine response (reduction in FEV1 ≥ 20% at or before 16 mg/ml). A total of 30 asthmatic subjects will be randomized (10 per arm) to a) aspirin, b) indomethacin or c) no intervention groups
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Aspirin | Active comparator | Drug: Aspirin |
| Indomethacin | Active comparator | Drug: Indomethacin |
| Control | No intervention | – |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Diagnosis of mild to moderate asthma
- No evidence of a previous asthma exacerbation in the preceding 6 weeks (defined as increased severity of respiratory symptoms requiring systemic steroids or escalation of therapy; b) asthma control questionnaire (ACQ) score less than 1.
Key exclusion criteria (12 listed)
- Diagnosis of severe asthma, vocal cord dysfunction, cystic fibrosis, COPD, CAD, hypertension, diabetes or renal failure that is not well controlled
- Greater than 10 pack-year history of smoking;
- Stopped smoking less than 1 year prior to study,
- Taking any aspirin or other NSAIDS on the week prior to bronchoscopy,
- Taking omega-3 fatty acid supplements
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 |
|---|---|---|
| Aspirin500 mg/8 h for 5 days | Drug | Aspirin |
| Indomethacin25 mg/8 h for 5 days | Drug | Indomethacin |
Primary outcome
Airway concentration of electrophilic fatty acids
Time frame: Change in the bronchoalveolar lavage concentration of electrophilic fatty acids from the first to the second bronchoscopy
Patients undergo a baseline bronchoscopy, afterwhich they are randomized to 5 days of a)indomethacin, b) aspirin, c) nothing . After treatment, another bronchoscopy is done. Outcomes are determined after each bronchoscopy
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 11 Jul 2017.
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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.
Fernando Holguin, MD MPH principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Aspirin and Indomethacin in people with Asthma and Electrophilic Fatty Acids, run by Sally E. Wenzel MD 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 2 inclusion and 12 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 11 Jul 2017. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Airway concentration of electrophilic fatty acids (time frame: Change in the bronchoalveolar lavage concentration of electrophilic fatty acids from the first to the second bronchoscopy). 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 11 Jul 2017.