Fluticasone and Salmeterol in Allergic Rhinitis
Condition: Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic
Study type: Interventional
Phase: Phase 4

Summary: 
      Allergic rhinitis is an under diagnosed global health problem which affects up to 25% of the
      population worldwide. It has been reported as being one of the 10 most common causes for
      attendance to primary care clinics. It is clinically defined as a symptomatic disorder of the
      nose induced by an IgE mediated inflammation following allergen exposure of the membranes
      lining the nose and is characterized by varying combinations of nasal symptoms including
      sneezing, nasal blockage, rhinorrhoea and itching. Intra nasal corticosteroids form the
      cornerstone of anti-inflammatory therapy in allergic rhinitis and there is increasing
      interest in the role of intranasal beta 2 agonists in the management of allergic rhinitis.
      The question therefore arises as to whether salmeterol exhibits such synergistic activity in
      the nose in terms of potentiating the steroid response of fluticasone.
    

Detailed description: 
      In vitro and ex vitro data have suggested that salmeterol may exhibit ligand independent
      activation of glucocorticoid receptors, which might result in potentiation of fluticasone by
      salmeterol when given in combination.

      Although no such evidence of synergy was reported with fluticasone salmeterol combination in
      the nose with allergen challenge, no data are available on nasal AMP challenge in the nose.

      This study compares the single and long term dosing effects of intranasal fluticasone alone,
      salmeterol alone and fluticasone salmeterol combination on nasal AMP challenge in persistent
      allergic rhinitis sufferers.

      Nasal corticosteroid,leukotriene receptor antagonist and anti histamine stopped for one week
      before the start of randomized treatment during the run in phase and wash out periods.
      Intransal sodium cromoglycate spray provided for rescue use throughout the study but witheld
      for at least twenty four hours before challenge.

      Nasal AMP challenges performed at baseline, after run-in and each washout, and 12 hours after
      the first and last evening dose of the study medication. A Zerostat Antistatic spacer (Cipla,
      Mumbai, India) used to administer the randomized treatments, adapted with a nasal olive for
      intranasal use instead of the conventional mouthpiece.

      The randomized treatments given once daily at night time as follows: placebo
      hydrofluoroalkane, 2 puffs (Cipla, Mumbai,India) salmeterol-hydrofluoroalkane, 2 puffs of 25
      g (Serevent Evohaler Allen and Hanburys, Middlesex, United Kingdom) fluticasone- salmeterol
      hydrofluoroalkane, 2 puffs of 250/25 g (Seretide Evohaler, Allen and Hanburys) and
      fluticasone-hydrofluoroalkane,2 puffs of 250 g (Flixotide Evohaler, Allen and Hanburys).

      The double-blind randomization process computer generated from www.randomization.com. Trial
      drug randomization performed under the direct supervision of the clinical trial pharmacist at
      Ninewells University Hospital.

      Active fluticasone,salmeterol, and fluticasone-salmeterol combination procured from
      GlaxoSmithKline (Allen and Hanburys) by the clinical trial pharmacy and matched placebo
      provided by Cipla.

      Following Informed Consent and screening visit, participants provided with randomized,
      labeled treatment packs with a single inhaler, either active or placebo at each study
      treatment visit.

      Blinding of patients and investigators ensured by using identical colored actuators for each
      treatment and labeling of active or placebo canisters with trial-specific labels.

      Measurements made at 12 hours after the first and last dose of each randomized treatment.

      At initial screening, nasal endoscopy performed to exclude significant nasal polyp disease
      (greater than grade 1), concha bullosa, and septal deviation.

      A Niox Flex nitric oxide analyzer (Aerocrine AB, Solna, Sweden) used to measure nasal nitric
      oxide. The standard aspiration technique recommended by the American Thoracic
      Society/European Respiratory Society guidelines used with a unilateral,nasal olive,
      breath-holding, and velum closure.

      For nasal AMP challenge, PNIF measured before and every 5 minutes for 60 minutes after 4
      squirts of 0.1 mL per actuation in each nostril of 400 mg/mL of AMP (ie, 320-mg total dose)
      delivered to the nose. The maximum decrease in PNIF measured using an In-check Nasal
      Inspiratory Flow Meter (Clement Clarke International Ltd, Harlow, United Kingdom).

      It has been shown that measuring PNIF (PEAK NASAL INSPIRATORY FLOW) response is more
      sensitive than measuring nasal airway resistance and is also more reproducible.PNIF
      correlates well vs symptoms in response to treatment in allergic rhinitis patients and has
      been shown to have a minimal clinically important difference of 5 L/min.

      At screening, patients instructed in the correct technique with particular attention to
      horizontal positioning of the meter, a closed mouth with maximal peak nasal inspiratory
      effort, and an adequate mask seal around the mouth and nose.

      Nasal impulse oscillometry measurements for nasal airway resistance at 5 Hz performed using a
      Jaeger MasterScreen impulse oscillometry system (Erich Jaeger, Hoechberg, Germany).

      The total nasal symptom 4 (TNS4) scores recorded at all visits, with a total score of 12 for
      the sum of the 4 separate domains for nasal blockage, run, itch, and sneeze, each rated from
      0 to 3.

      The Juniper Mini Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ) completed by
      the participant immediately before and a week after each randomized treatment. The global
      RQLQ is the mean of the 5 individual domains, with individual domains scored from 0 to 6.

      Serum eosinophilic cationic protein measured using an enzyme-linked immunoassay technique
      (UniCAP; Sweden Diagnostics UK Ltd, Milton Keyes, United Kingdom).
    

Intervention name(s): FLUTICASONE PROPRIONATE; Salmeterol; PLACEBO
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 1. Fluticasone Propionate (FP) Product name: Flixotide Evohaler® Manufacturer: Allan and Hanbury's Active ingredients: Fluticasone Propionate Propellant: HFA 134a Dose: 250μg per actuation giving a total dose of 500µg per day through the spacer device with the customised nasal adaptor.; Salmeterol Product Name: Serevent® Manufacturer: Allan and Hanbury's Active ingredients: Salmetrol Xinafoate Propellant: HFA 134a Dose: 25μg per actuation giving a total dose of 50µg per day through the spacer device with the customised nasal adaptor; 4. Placebo inhaler to SM, FP, SM+FP Manufacturer: Cipla Ltd Active ingredients: None Propellants: HFA 134a Imported & QP release tested in UK : DHP Clinical supplies, Powys, UK
Other intervention name(s): Treatment; Treatment; Treatment
Intervention MeSH terms: Fluticasone; Salmeterol Xinafoate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment