Clinical trial NCT02953106: Effects of Intranasal Fluticasone Plus Azelastine on Airway Inflammation in Patients With Asthma & Allergic Rhinitis
Official title: Proof of Concept Study to Assess Downstream Effects of Using Combined Intranasal Fluticasone Propionate Plus Azelastine Nasal Spray on Asthmatic Inflammation in Patients With Persistent Asthma and Allergic Rhinitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Asthma, Allergic
Rhinitis,Allergic
Allergy
Keywords: Asthma
Rhinitis
Dymista
allergy
Lead sponsor: University of Dundee
Sponsor class: OTHER
First posted: 2016-11-02
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Single centre, double-blind, placebo controlled, adaptive design, cross-over trial. The primary objective is to assess the additive effects of using combined intranasal fluticasone propionate plus azelastine nasal spray on airway hyperresponsiveness. This is in patients with persistent asthma and allergic rhinitis, receiving inhaled steroid.

Detailed description: The unified allergic airway describes patients who have both asthma and allergic rhinitis. Both conditions have similar underlying pathophysiology in terms of T-helper 2 (Th2) cell activation. Patients with unified allergic airway disease have a greater burden in terms of impaired quality of life, and the presence of airway hyper-responsiveness (AHR) to methacholine is a hallmark of their underlying asthmatic inflammatory process. Targeting the Th2 allergic airway with a topical antihistamine may improve airway hyperresponsiveness.

It has previously been shown that in patients with unified allergic airway disease, using inhaled fluticasone alone (100 micrograms per day) produced a 1.2 doubling dilution (dd) shift in the provocative concentration of methacholine required to reduce forced expiratory volume (FEV1) by 20% (PC20). However when adding nasal fluticasone to the inhaled steroid, there was a 1.79 dd shift. This difference (0.58 dd, 95% CI 0.78, 1.95) was not statistically significant. However the combined treatment did result in significant improvement in rhinitis quality of life, nasal inflammation and inspiratory flow.

The investigators will repeat this previous concept, but compare intranasal fluticasone with azelastine (an antihistamine) nasal spray versus placebo nasal spray, in atopic asthmatic patients on inhaled steroid. This will be to assess effects on methacholine PC20, the primary outcome, and to assess the effects on the following secondary outcomes: Exhaled nitric oxide (FeNO), FEV1, morning peak expiratory flow (PEF), impulse oscillometry, peak nasal inspiratory flow (PNIF), nasal nitric oxide (NO), blood eosinophils, eosinophilic cationic protein (ECP), nasal symptoms, asthma control and quality of life; and rhinitis quality of life.

Twenty adults 18 and up, with allergic asthma will be enrolled. They will have a run-in on 2 weeks of 200 micrograms beclometasone inhaler and then be randomised to add either intranasal fluticasone and azelastine, or placebo nasal spray to their treatment (double blind). Treatment period one will be 3-5 weeks followed by a washout of 2-4 weeks, and crossover to treatment period two for 3-5 weeks. Due to the crossover nature of this study participants will receive both treatments in random order. There will be an Interim analysis after 20 participants complete the study per protocol and the exact required sample size will be recalculated (Pocock/adaptive design).

Eligibility criteria: Inclusion Criteria:

* Male or female volunteers, aged 18 years and above, with persistent asthma and allergic rhinitis
* On a minimum of 200μg BDP of Inhaled corticosteroid (ICS)
* FEV1 ≥ 60 % predicted
* Positive skin prick test, or record of elevated allergen-specific IgE to at least 1 perennial allergen
* Methacholine PC20 \< 8mg/ml at Visit 1
* Ability to give informed consent

Exclusion Criteria:

* Other respiratory diseases such as COPD, bronchiectasis or allergic bronchopulmonary aspergillosis (ABPA) which are considered to be significant in the opinion of the study physician Nasal polyps ≥ Grade 2
* An asthma exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month of the study commencement, or 3 months if hospital admission was required
* Any clinically significant medical condition that may endanger the health or safety of the participant. For example: Patients who have tuberculosis or any type of untreated infection or have had recent surgical operation or injury to the nose or mouth.
* Participation in another trial within 30 days before the commencement of the study
* Pregnancy or lactation
* Unable to comply with the procedures of the protocol
* Unable or unwilling to consent
* Taking prohibited medications as listed in section 6.7.2 Prohibited Medications
* Hypersensitivity to the active substances or to any of the excipients of Dymista Nasal Spray.

Primary outcomes:
measure: Methacholine PC20
timeFrame: 3-5 weeks
Secondary outcomes:
measure: Exhaled nitric oxide (FeNO)
timeFrame: 3-5 weeks
measure: Forced expiratory volume in 1 second (FEV1)
timeFrame: 3-5 weeks
measure: Morning peak expiratory flow (PEF)
timeFrame: 3-5 weeks
measure: Airway resistance at 5Hz (R5)
timeFrame: 3-5 weeks
measure: Airway resistance at 20Hz (R20)
timeFrame: 3-5 weeks
measure: Peripheral airway resistance (R5-R20)
timeFrame: 3-5 weeks
measure: Airway Reactance (X5)
timeFrame: 3-5 weeks
measure: Airway Reactance area under the curve (AX)
timeFrame: 3-5 weeks
measure: Domiciliary peak nasal inspiratory flow (PNIF)
timeFrame: 3-5 weeks
measure: Nasal nitric oxide (NO)
timeFrame: 3-5 weeks
measure: Blood eosinophils
timeFrame: 3-5 weeks
measure: Eosinophilic cationic protein (ECP)
timeFrame: 3-5 weeks
measure: Total nasal symptom score (TNS4)
timeFrame: 3-5 weeks
measure: Asthma control questionnaire (ACQ)
timeFrame: 3-5 weeks
measure: Asthma quality of life questionnaire (AQLQ)
timeFrame: 3-5 weeks
measure: Rhinitis quality of life questionnaire (RQLQ)
timeFrame: 3-5 weeks
measure: Visual analogue scale (VAS)
timeFrame: 3-5 weeks
Other outcomes:
Locations:
city: Dundee
country: United Kingdom
facility: Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School
state: Scotland
Study officials:
affiliation: Scottish Centre for Respiratory Reseach
name: Brian Lipworth, MD
role: PRINCIPAL_INVESTIGATOR
References: