Electrophilic Fatty Acid Derivatives in Asthma (EFADA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
Fernando Holguin, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01733485
First received: November 15, 2012
Last updated: November 26, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Asthma
Electrophilic Fatty Acids
Drug: Aspirin
Drug: Indomethacin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Electrophilic Fatty Acid Derivatives in Asthma

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 30
Study Start Date: October 2011
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aspirin Drug: Aspirin
500 mg/8 h for 5 days
Active Comparator: Indomethacin Drug: Indomethacin
25 mg/8 h for 5 days
No Intervention: Control

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

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01733485

Contacts
Contact: Sabrina Malik, MPH 4128642915 maliks2@upmc.edu

Locations
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15206
Contact: Sabrina Malik, MPH    412-864-2915    maliks2@upmc.edu   
Contact: Fernando Holguin, MD, MPH    4126922817    holguinf@upmc.edu   
Principal Investigator: Fernando Holguin, MD, MPH         
Sponsors and Collaborators
University of Pittsburgh
  More Information

No publications provided

Responsible Party: Fernando Holguin, Assistant Professor of Medicine, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01733485     History of Changes
Other Study ID Numbers: U10 HL098177
Study First Received: November 15, 2012
Last Updated: November 26, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Asthma
Electrophilic Fatty Acids
Inflammation

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Aspirin
Indomethacin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics

ClinicalTrials.gov processed this record on August 28, 2014