Factors Involved in Dymista's Superior Clinical Efficacy in the Treatment of Seasonal Allergic Rhinitis

NCT ID: NCT02402465

Last Updated: 2024-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2020-02-29

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.

Conditions

Allergic Rhinitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo nasal spray that is similar to Dymista in all respects except the active ingredient

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients will be treated by placebo

Nasal Allergen Challenge

Intervention Type: PROCEDURE

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

Fluticasone propionate

Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista

Group Type: EXPERIMENTAL

Fluticasone propionate

Intervention Type: DRUG

Patients will receive fluticasone nasal spray

Nasal Allergen Challenge

Intervention Type: PROCEDURE

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

Dymista (fluticasone/azelastine)

Dymista is also provided as a nasal spray in bottles similar to the other two agents

Group Type: EXPERIMENTAL

Fluticasone/Azelastine nasal spray

Intervention Type: DRUG

Patients will receive Dymista nasal spray

Nasal Allergen Challenge

Intervention Type: PROCEDURE

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

Interventions

Placebo

Patients will be treated by placebo

Intervention Type: DRUG

Fluticasone propionate

Patients will receive fluticasone nasal spray

Intervention Type: DRUG

Fluticasone/Azelastine nasal spray

Patients will receive Dymista nasal spray

Intervention Type: DRUG

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

Intervention Type: PROCEDURE

Other Intervention Names

saline; Flonase; Dymista; Nasal provocation

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fuad M Baroody, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

The University of Chicago Medicine

Chicago, Illinois, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

IRB14-1199

Identifier Type: -

Identifier Source: org_study_id