Evaluating Factors Involved in Dymista's Superior Clinical Efficacy to Fluticasone Propionate in the Treatment of Seasonal Allergic Rhinitis

Allergic Rhinitis Clinical Trial

Official title:

Evaluating Factors Involved in Dymista's Superior Clinical Efficacy to Fluticasone Propionate in the Treatment of Seasonal Allergic Rhinitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02402465
• Other study ID #: 14-1199
• Status: Recruiting
• Phase: Phase 4
• First received: March 18, 2015
• Last updated: July 19, 2016
• Start date: February 2015
• Est. completion date: December 2017

Study information

• Verified date: July 2016
• Source: University of Chicago
• Contact: Fuad M Baroody, MD
• Phone: 773-702-4790
• Email: fbaroody[@]surgery.bsd.uchicago.edu
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Allergic Rhinitis
• Rhinitis
• Rhinitis, Allergic
• Rhinitis, Allergic, Seasonal

Intervention

Drug:
• Placebo
Patients will be treated by placebo
• Fluticasone propionate
Patients will receive fluticasone nasal spray
• Fluticasone/Azelastine nasal spray
Patients will receive Dymista nasal spray

Procedure:
• Nasal Allergen Challenge
All subjects will receive a nasal challenge with allergen to mimick an allergic response and allow the investigation of the different drug effects on that response. Allergen extracts will be used as sprays into the nasal cavity. The extracts are approved by FDA for skin testing or desensitization therapy and an IND was obtained to allow intranasal administration

Locations

Country	Name	City	State
United States	The University of Chicago Medicine	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total Nasal Symptom Score	We will evaluate the total nasal symptoms (sum of itchy, runny, sneezing, and congestion scores, filled on a scale from 0-3) after allergen challenge and evaluate the effect of the interventions on these symptom scores.	Total nasal symptoms after allergen challenge. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and Total nasal symptom score is recorded for the 10 minute period after each of the challenges	No
Other	Lactoferrin	We will evaluate the effects of the different interventions on the levels of lactoferrin in nasal lavages after allergen challenges	Lactoferrin levels in nasal lavages after allergen challenges. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and lavages are collected 10 minutes after each of these challenges	No
Other	Eosinophils	We will count number of eosinophils in nasal lavages at the beginning of each challenge and evaluate the effects of the different treatments	Number of eosinophils in the first nasal lavage of the challenge. There will be 3 consecutive challenges separated by 24 hrs and eosinophils will be counted in the first lavage of each challenge	No
Other	Histamine	We will evaluate the effects of the different interventions on the levels of histamine in nasal lavages after allergen challenges	Histamine levels in nasal lavages after allergen challenges. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and lavages are collected 10 minutes after each of these challenges	No
Other	Tryptase	We will evaluate the effects of the different interventions on the levels of tryptase in nasal lavages after allergen challenges	Tryptase levels in nasal lavages after allergen challenges. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and lavages are collected 10 minutes after each of these challenges	No
Other	Eosinophil cationic protein (ECP)	We will measure levels of ECP in nasal lavages at the beginning of each challenge and evaluate the effects of the different treatments	Levels of ECP in the first nasal lavage of the challenge.There will be 3 consecutive challenges separated by 24 hrs and ECP will be measured in the first lavage of each challenge	No
Primary	Albumin level in nasal lavage	We will calculate the total change of albumin levels after the allergen challenges and subtract the diluent (sham) response for a single value that will reflect the increase in vascular permeability after allergen challenges on the first day after treatment with the 3 different agents. This will be compared between therapies	Change in Albumin level after the first nasal challenge on each treatment arm. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and lavages are collected 10 minutes after each of these challenges	No
Secondary	Sneezes after allergen challenge	We will evaluate the effects of the different interventions on the number of sneezes after allergen challenges	Number of sneezes after allergen challenges. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and sneezes are counted in a 10 minute period after each of the challenges	No