Standardising Nasal Allergen Challenge in Adult With Hay Fever
Condition: Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic
Study type: Interventional

Summary: 
      Hay fever affects 1 in 4 of the UK population and has significant effects on the quality of
      life of sufferers. Allergy to grass pollen is the most common cause. A detailed understanding
      of the mechanisms involved during allergic reactions to pollens in hay fever sufferers may
      provide improvements in diagnosis, drug treatment and assessment of their response to
      treatment.

      Controlled exposures to allergens such as grass pollen can provide important information on
      the mechanisms of allergic inflammation and may be used to assess the success of anti-allergy
      treatments.

      Nasal allergen challenge (NAC) is a useful tool in the investigation of allergic rhinitis,
      including grass pollen-induced seasonal allergic rhinitis (hay fever). NAC is performed by
      installation of a very small amount of grass pollen extract into the nose in order to
      reproduce mild and short-lived symptoms such as nasal itch, sneezing, runny nose and nasal
      congestion that you experience in a more severe form during natural exposure to grass pollen
      during the summer. Nasal allergen challenge has allowed us to explore the mechanism of hay
      fever and to provide a rapid and reliable method for investigating new potential treatments
      for hay fever.

      Nasal allergen Challenge is a very well-standardised and safe procedure that has been
      performed within the department of Allergy and Clinical Immunology at Imperial College and
      Royal Brompton Hospital for many years.

      Unfortunately the grass pollen extract ('Aquagen') that we have routinely used for nasal
      challenge has been discontinued and is therefore no longer available. The present study
      involves testing an alternative source of the grass pollen extract in the form of 'Grazax'
      which is a freeze-dried tablet that is highly standardised and should enable us to give an
      identical amount of grass pollen extract for the purpose of nasal challenge. We plan a
      'head-to-head' comparison of the two extracts in nasal challenge in order to confirm that the
      two sources of allergen are equivalent thereby enabling us to use Grazax as the source of
      grass pollen extract for our nasal challenge studies in the future.
    

Detailed description: 
      Nasal allergen challenge (NAC) is a useful tool in the investigation of allergic rhinitis,
      including grass pollen-induced seasonal allergic rhinitis (hay fever). We have experience in
      using NAC to investigate the clinical and immunological effects of allergen exposure and in
      using NAC as a surrogate outcome to assess the efficacy of treatments for allergic rhinitis.
      The procedure is safe and well tolerated. In order for NAC to be a valid tool, it is
      essential that the allergen extracts used are standardised in terms of concentration and
      stability in solution. We have previously used an extract of Timothy Grass (Phleum pratense)
      pollen, Aquagen (ALK-Abello, Denmark). Aquagen is supplied as a dry powder, to be
      reconstituted prior to use by dissolving in an albumin-based diluent. Unfortunately, Aquagen
      production has been discontinued, but the identical allergen is now available as Timothy
      Grass lyophilisate tablet, Grazax (ALK-Abello), an approved and licensed product for
      treatment of severe seasonal allergic rhinitis. Grazax consists of purified, freeze-dried
      Timothy Grass pollen extract, plus only three excipients, gelatin (from fish), mannitol and
      sodium hydroxide. Preliminary investigations have shown that Grazax tablets can be dissolved
      in saline to produce identical concentrations of allergen to Aquagen, with the same stability
      profile in vitro. We anticipate therefore, that the clinical effect when used for nasal
      allergen challenges would be equivalent to the use of Aquagen for a given allergen
      concentration. In this study we intend to confirm that nasal symptoms produced during the NAC
      with either Aquagen or Grazax will be equivalent. We will recruit volunteers with grass
      pollen-induced hay fever to undergo NAC with each allergen source, sequentially. In an open,
      randomised-order, cross-over study. The primary outcome will be patient-reported nasal
      symptoms (according to a standardised scoring system) in the 60 minutes after each nasal
      challenge.
    

Intervention name(s): Aquagen; Grazax
Intervention type(s): Diagnostic Test; Diagnostic Test
Intervention description(s): To compare the clinical allergic response after direct installation of an aqueous solution of Aquagen Timothy Grass pollen extract via nasal allergen challenge with the clinical allergic response after direct installation of an aqueous solution of Grazax Timothy Grass lyophilisate tablets via nasal allergen challenge in grass pollen allergic individuals.; To compare the clinical allergic response after direct installation of an aqueous solution of Aquagen Timothy Grass pollen extract via nasal allergen challenge with the clinical allergic response after direct installation of an aqueous solution of Grazax Timothy Grass lyophilisate tablets via nasal allergen challenge in grass pollen allergic individuals.
Other intervention name(s): Grazax Timothy Grass lyophilisate tablet
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a single group study assessing symptoms scores 4 weeks between the two assessments (Grazax NAC and Aquagen NAC) performed to avoid any carry-over effects of this cross-over design.
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Grass pollen allergy; Hayfever; Atopy; Allergic rhinitis; Nasal allergen challenge