Clinical trial NCT02402465: Factors Involved in Dymista's Superior Clinical Efficacy in the Treatment of Seasonal Allergic Rhinitis
Official title: Evaluating Factors Involved in Dymista's Superior Clinical Efficacy to Fluticasone Propionate in the Treatment of Seasonal Allergic Rhinitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Allergic Rhinitis
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2015-03-30
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Dymista, a combined product containing the antihistamine azelastine and the intranasal steroid fluticasone, provides superior clinical efficacy to both fluticasone propionate and azelastine hydrochloride in the treatment of seasonal allergic rhinitis. The superiority of efficacy not only occurs at the initiation of treatment, but persists for its duration. The mechanism underlying the superior efficacy of Dymista is not known. This trial focuses on examining the effects of Dymista on the dynamics of the allergic response in man using nasal provocation with antigen. The investigators will study the relationship between symptoms, physiology, cells and mediators.

Detailed description: The main hypothesis for the trial is that Dymista affects multiple phases of the allergic response, which in sum are greater than the effects of fluticasone propionate or azelastine hydrochloride alone.

Our objectives for this study are to demonstrate:

1. that the induction of allergic inflammation by nasal provocation with antigen causes a cellular infiltration, with subsequent release of inflammatory biomarkers that cause augmented responses to subsequent exposure to antigens.
2. that fluticasone prevents allergic inflammation from developing after antigen challenge and subsequently prevents the augmentation of the nasal response to nasal challenge with antigen.
3. that the azelastine in Dymista reduces the effects of released histamine

To address these hypotheses we will perform a 3-way, randomized, placebo-controlled, and crossover trial. We will recruit 20 asymptomatic seasonal allergic rhinitis patients outside of the relevant season. The subjects will receive placebo, fluticasone propionate and Dymista. The nasal provocations will be separated by 2 weeks. Treatment will begin 15 minutes before nasal provocation with ragweed or grass antigen and the treatment will continue twice a day for 3 days. Nasal provocation will occur daily for three days to evaluate for priming (increased sensitization with repeated antigen exposure, which mimics seasonal disease where antigen exposure occurs in the setting of continued allergic inflammation). For outcome measures, we will monitor both nasal symptoms after nasal provocation as well as collect nasal lavage to evaluate effects on eosinophils and biomarkers of the immune response. In the nasal lavage, we will quantify the number of eosinophils (a marker of cellular recruitment) and measure the levels of histamine (a marker of basophil and mast cell activation), tryptase (a marker of mast cell activation), albumin (a marker of vascular permeability), lactoferrin (a marker of glandular activation) and ECP (a marker of eosinophil activation). Thus we expect to generate information on both clinical effects and physiologic differences between the treatments.

Eligibility criteria: Inclusion Criteria:

1. Males and females between 18 and 55 years of age.
2. History of grass and/or ragweed allergic rhinitis.
3. Positive skin test to grass and/or ragweed antigen.
4. Positive response to screening nasal challenge.
5. Off all anti-allergic medications for a minimum of 2 weeks.

Exclusion Criteria:

1. Physical signs or symptoms suggestive of renal, hepatic or cardiovascular disease.
2. Pregnant or lactating women.
3. Upper respiratory infection within 14 days of study start.

Primary outcomes:
measure: Change From Baseline Response in Albumin Levels in Nasal Lavage Following Each Challenge
timeFrame: 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
Secondary outcomes:
measure: Sneezes After Allergen Challenge
timeFrame: 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
Other outcomes:
measure: Total Nasal Symptom Score
timeFrame: 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
measure: Change From Baseline Response in Lactoferrin Levels in Nasal Lavage Following Each Challenge
timeFrame: 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
measure: Eosinophils
timeFrame: 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
measure: Histamine
timeFrame: 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
measure: Tryptase
timeFrame: 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
measure: Eosinophil Cationic Protein (ECP)
timeFrame: 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
Locations:
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
Study officials:
affiliation: University of Chicago
name: Fuad M Baroody, MD
role: PRINCIPAL_INVESTIGATOR
References: