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

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ClinicalTrials.gov Identifier: NCT02402465
Recruitment Status : Unknown
Verified July 2016 by University of Chicago.
Recruitment status was:  Recruiting
First Posted : March 30, 2015
Last Update Posted : July 20, 2016
Sponsor:
Information provided by (Responsible Party):
University of Chicago

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.

Condition or disease Intervention/treatment Phase
Allergic Rhinitis Drug: Placebo Drug: Fluticasone propionate Drug: Fluticasone/Azelastine nasal spray Procedure: Nasal Allergen Challenge Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Evaluating Factors Involved in Dymista's Superior Clinical Efficacy to Fluticasone Propionate in the Treatment of Seasonal Allergic Rhinitis
Study Start Date : February 2015
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hay Fever

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo nasal spray that is similar to Dymista in all respects except the active ingredient
Drug: Placebo
Patients will be treated by placebo

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

Experimental: Fluticasone propionate
Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista
Drug: Fluticasone propionate
Patients will receive fluticasone 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

Experimental: Dymista (fluticasone/azelastine)
Dymista is also provided as a nasal spray in bottles similar to the other two agents
Drug: Fluticasone/Azelastine nasal spray
Patients will receive Dymista nasal spray
Other Name: Dymista

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




Primary Outcome Measures :
  1. Albumin level in nasal lavage [ 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 ]
    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 :
  1. Sneezes after allergen challenge [ 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 ]
    We will evaluate the effects of the different interventions on the number of sneezes after allergen challenges


Other Outcome Measures:
  1. Total Nasal Symptom Score [ 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 ]
    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.

  2. Lactoferrin [ 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 ]
    We will evaluate the effects of the different interventions on the levels of lactoferrin in nasal lavages after allergen challenges

  3. Eosinophils [ 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 ]
    We will count number of eosinophils in nasal lavages at the beginning of each challenge and evaluate the effects of the different treatments

  4. Histamine [ 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 ]
    We will evaluate the effects of the different interventions on the levels of histamine in nasal lavages after allergen challenges

  5. Tryptase [ 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 ]
    We will evaluate the effects of the different interventions on the levels of tryptase in nasal lavages after allergen challenges

  6. Eosinophil cationic protein (ECP) [ 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 ]
    We will measure levels of ECP in nasal lavages at the beginning of each challenge and evaluate the effects of the different treatments



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02402465


Contacts
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Contact: Fuad M Baroody, MD 773-702-4790 fbaroody@surgery.bsd.uchicago.edu
Contact: Debbie Hawes 773-702-4790 dhawes@surgery.bsd.uchicago.edu

Locations
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United States, Illinois
The University of Chicago Medicine Recruiting
Chicago, Illinois, United States, 60637
Contact: Fuad M Baroody, MD    773-702-4790    fbaroody@surgery.bsd.uchicago.edu   
Contact: Debbie Hawes    773-702-4790    dhawes@surgery.bsd.uchicago.edu   
Sponsors and Collaborators
University of Chicago

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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02402465    
Other Study ID Numbers: 14-1199
First Posted: March 30, 2015    Key Record Dates
Last Update Posted: July 20, 2016
Last Verified: July 2016
Additional relevant MeSH terms:
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Rhinitis
Rhinitis, Allergic
Rhinitis, Allergic, Seasonal
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Azelastine
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Lipoxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Histamine H1 Antagonists, Non-Sedating
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents