Clinical trial NCT01320072: Diagnosis of Aspirin Hypersensitivity in Aspirin Exacerbated Respiratory Disease
Official title: Diagnosis of Aspirin Hypersensitivity in Aspirin Exacerbated Respiratory Disease Using a Safe, Low Dose Aspirin Challenge
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Asthma, Aspirin-induced
Keywords: aspirin
asthma
diagnosis
prostaglandins
leukotrienes
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2011-03-22
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Allergy/Immunology clinic population in Bronx, NY

Brief summary: To diagnose aspirin hypersensitivity in asthmatics by using and safe, low-dose aspirin oral challenge.

Hypothesis 1: A low dose of oral ASA (20 or 40 mg) will induce significantly different concentrations of arachidonic acid metabolites in ASA-sensitive asthmatics as compared to ASA-tolerant asthmatics.

Hypothesis 2: The low dose (20 or 40 mg) ASA challenge will be well tolerated by ASA-sensitive asthmatics.

Detailed description: This research study is being conducted within the established Airway Research Group at Montefiore Medical Center and Albert Einstein College of Medicine in Bronx, NY. The patient population in the Bronx has one of the highest asthma prevalences in the country. Thus, our study participants are being recruited among the population most in need of a better understanding of the disease process.

Visits 1 and 2: Low-dose challenge with 20 mg and 40 mg of ASA. ASA will be administered orally to participants in both groups: 20 mg at Visit 1 and 40 mg at Visit 2. Visits will take place at least 1 week apart. Blood and urine will be collected at several time points.

Visit 3: Oral graded ASA challenge will be performed to confirm or rule out the presence of ASA-hypersensitivity. This visit will take place at least 1 week after Visit 2. Both groups will undergo an oral graded ASA challenge as per earlier described protocol. Urine and plasma will be collected from the patients at several time points. Hypersensitivity reactions will be defined in four different ways: a) decline in forced expiratory volume in 1 second (FEV1) of at least 15% combined and naso-ocular reaction; b) 20% decline in FEV1; c) isolated naso-ocular reactions; d) isolated cutaneous reactions (hives and swelling). Patients with reactions will be treated according to their symptoms.

Eligibility criteria: Inclusion Criteria:

1. Participants of both sexes aged 18 years and older.
2. Patients with a history of ASA-induced asthma who had at least one asthma attack after ingestion of aspirin or other NSAIDs.
3. Patients with a history of ASA-tolerant asthma who had been occasionally using aspirin or other NSAIDs without any adverse reactions.

Exclusion Criteria:

1. Mental or legal incapacitation, or significant emotional problems, or a history of psychiatric disorders at the time of the enrollment.
2. Pregnancy or breastfeeding at the time of enrollment.
3. History of a severe anaphylactic reaction precipitated by ASA and/or other NSAIDs (such as ibuprofen, naproxen, indomethacin, Advil, Aleve, Motrin, diclofenac, etc.).
4. History of a severe bronchospasm precipitated by ASA and/or other NSAIDs requiring an endotracheal intubation.
5. Chronic kidney disease (a calculated GFR based on the Modification of Diet in Renal Disease (MDRD) equation is \< 60 mL/min/1.73 sq.meter).
6. Chronic liver disease by history and/or abnormal liver function tests (SGOT and SGPT ≥ 3 times above upper normal range).
7. Baseline FEV1 \< 70% (or \< 1.5 L) of predicted, or an exacerbation of asthma in the 6 weeks preceding the study.
8. An active infectious disease.
9. Anemia that requires work-up, black stools, active bleeding.
10. A history of gastrointestinal bleeding due to aspirin or other NSAIDS, gastritis, or duodenal ulcer not proven to be due to Helicobacter pylori.
11. A history of hemophilia or any other bleeding disorder.
12. Unstable angina.
13. Participants taking aspirin and or other NSAIDs at the time of the study visits.
14. Participants taking leukotriene receptors inhibitors or 5-lypooxygenase (5-LO) inhibitors at the time of the study visits.
15. In addition, participants taking one or more of the following drugs intake last 14 days prior to the enrollment will be excluded: lithium, warfarine, enoxaparin, heparin, dalteparin, fluconazole, ketotifen. Short-acting antihistamines should be stopped 5 days before the challenge; long-acting antihistamines should be stopped 1 week prior to the challenge.

Primary outcomes:
measure: Eicosanoid Metabolites Concentration
timeFrame: 2 hours
Secondary outcomes:
measure: Treatment-Related Adverse Events
timeFrame: 24 hours after the challenge
measure: Change in Forced Expiratory Volume in One Second (FEV1) in Aspirin Exacerbated Respiratory Disease (AERD) Patients
timeFrame: 12 months
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Attending physician
name: Elina Jerschow, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jerschow E, Ren Z, Hudes G, Sanak M, Morales E, Schuster V, Spivack SD, Rosenstreich D. Utility of low-dose oral aspirin challenges for diagnosis of aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol. 2016 Apr;116(4):321-328.e1. doi: 10.1016/j.anai.2015.12.026. Epub 2016 Jan 25.