Evaluating Factors Involved in Dymista's Superior Clinical Efficacy to Fluticasone Propionate in the Treatment of Seasonal Allergic Rhinitis
Primary Purpose
Allergic Rhinitis
Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Placebo
Fluticasone propionate
Fluticasone/Azelastine nasal spray
Nasal Allergen Challenge
Sponsored by
About this trial
This is an interventional basic science trial for Allergic Rhinitis
Eligibility Criteria
Inclusion Criteria:
- Males and females between 18 and 55 years of age.
- History of grass and/or ragweed allergic rhinitis.
- Positive skin test to grass and/or ragweed antigen.
- Positive response to screening nasal challenge.
- Off all anti-allergic medications for a minimum of 2 weeks.
Exclusion Criteria:
- Physical signs or symptoms suggestive of renal, hepatic or cardiovascular disease.
- Pregnant or lactating women.
- Upper respiratory infection within 14 days of study start.
Sites / Locations
- The University of Chicago MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
Fluticasone propionate
Dymista (fluticasone/azelastine)
Arm Description
Placebo nasal spray that is similar to Dymista in all respects except the active ingredient
Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista
Dymista is also provided as a nasal spray in bottles similar to the other two agents
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Sneezes after allergen challenge
We will evaluate the effects of the different interventions on the number of sneezes after allergen challenges
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02402465
Brief Title
Evaluating Factors Involved in Dymista's Superior Clinical Efficacy to Fluticasone Propionate 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
2. Study Status
Record Verification Date
July 2016
Overall Recruitment Status
Unknown status
Study Start Date
February 2015 (undefined)
Primary Completion Date
December 2017 (Anticipated)
Study Completion Date
December 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
4. Oversight
Data Monitoring Committee
No
5. Study Description
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:
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.
that fluticasone prevents allergic inflammation from developing after antigen challenge and subsequently prevents the augmentation of the nasal response to nasal challenge with antigen.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allergic Rhinitis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo nasal spray that is similar to Dymista in all respects except the active ingredient
Arm Title
Fluticasone propionate
Arm Type
Experimental
Arm Description
Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista
Arm Title
Dymista (fluticasone/azelastine)
Arm Type
Experimental
Arm Description
Dymista is also provided as a nasal spray in bottles similar to the other two agents
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Patients will be treated by placebo
Intervention Type
Drug
Intervention Name(s)
Fluticasone propionate
Intervention Description
Patients will receive fluticasone nasal spray
Intervention Type
Drug
Intervention Name(s)
Fluticasone/Azelastine nasal spray
Other Intervention Name(s)
Dymista
Intervention Description
Patients will receive Dymista nasal spray
Intervention Type
Procedure
Intervention Name(s)
Nasal Allergen Challenge
Intervention Description
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
Primary Outcome Measure Information:
Title
Albumin level in nasal lavage
Description
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
Time Frame
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
Secondary Outcome Measure Information:
Title
Sneezes after allergen challenge
Description
We will evaluate the effects of the different interventions on the number of sneezes after allergen challenges
Time Frame
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
Other Pre-specified Outcome Measures:
Title
Total Nasal Symptom Score
Description
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.
Time Frame
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
Title
Lactoferrin
Description
We will evaluate the effects of the different interventions on the levels of lactoferrin in nasal lavages after allergen challenges
Time Frame
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
Title
Eosinophils
Description
We will count number of eosinophils in nasal lavages at the beginning of each challenge and evaluate the effects of the different treatments
Time Frame
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
Title
Histamine
Description
We will evaluate the effects of the different interventions on the levels of histamine in nasal lavages after allergen challenges
Time Frame
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
Title
Tryptase
Description
We will evaluate the effects of the different interventions on the levels of tryptase in nasal lavages after allergen challenges
Time Frame
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
Title
Eosinophil cationic protein (ECP)
Description
We will measure levels of ECP in nasal lavages at the beginning of each challenge and evaluate the effects of the different treatments
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Males and females between 18 and 55 years of age.
History of grass and/or ragweed allergic rhinitis.
Positive skin test to grass and/or ragweed antigen.
Positive response to screening nasal challenge.
Off all anti-allergic medications for a minimum of 2 weeks.
Exclusion Criteria:
Physical signs or symptoms suggestive of renal, hepatic or cardiovascular disease.
Pregnant or lactating women.
Upper respiratory infection within 14 days of study start.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fuad M Baroody, MD
Phone
773-702-4790
Email
fbaroody@surgery.bsd.uchicago.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Debbie Hawes
Phone
773-702-4790
Email
dhawes@surgery.bsd.uchicago.edu
Facility Information:
Facility Name
The University of Chicago Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fuad M Baroody, MD
Phone
773-702-4790
Email
fbaroody@surgery.bsd.uchicago.edu
First Name & Middle Initial & Last Name & Degree
Debbie Hawes
Phone
773-702-4790
Email
dhawes@surgery.bsd.uchicago.edu
12. IPD Sharing Statement
Learn more about this trial
Evaluating Factors Involved in Dymista's Superior Clinical Efficacy to Fluticasone Propionate in the Treatment of Seasonal Allergic Rhinitis
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