title: Protocol for a randomised, double-blind, placebo-controlled study of grass allergen immunotherapy tablet for seasonal allergic rhinitis: time course of nasal, cutaneous and immunological outcomes.
abstract: BACKGROUND
  Seasonal Allergic Rhinitis is characterised by inflammation of the nasal mucosa upon exposure to common aeroallergens, affecting up to 20-25 % of the population. For those patients whose symptoms are not controlled by standard medical treatment, allergen specific immunotherapy is a therapeutic alternative. Although several studies have shown changes in immunologic responses as well as long term tolerance following treatment with a sublingual allergy immunotherapy tablet, a detailed time course of the early mechanistic changes of local and systemic T and B cell responses and the effects on B cell repertoire in the nasal mucosa have not been fully examined.
  
  
  METHODS
  This is a randomized, double-blind, single-centre, placebo controlled, two arm time course study based in the United Kingdom comparing sublingual allergy immunotherapy tablet (GRAZAX(®), ALK-Abello Horsholm, Denmark) plus standard treatment with placebo plus standard treatment. Up to 50 moderate to severe grass pollen allergic participants will be enrolled to ensure randomisation of at least 44. Further, we shall enrol 20 non-atopic volunteers. Screening will be completed before eligible atopic participants are randomised to one of the two treatment arms in a 1 to 1 ratio. The primary endpoint will be the total nasal symptom score assessed over 60 min following grass pollen nasal allergen challenge after 12 months of treatment. Clinical assessments and/or mechanistic analyses on blood, nasal fluid, brushing and biopsies will be performed at baseline at 1, 2, 3, 4 (coinciding with the peak pollen season), 6 and 12 months of treatment. After 12 months of treatment, unblinding will take place. Those atopic participants receiving active treatment will continue therapy for another 12 months followed by a post treatment phase of 12 months. Assessments and collection of biologic samples from these participants will take place again at 24 and at 36 months from the start of treatment. The 20 healthy, non-atopic controls will undergo screening and one visit only coinciding with the 12 month visit for the atopic participants.
  
  
  CONCLUSIONS
  The trial will end in April 2017. The trial is registered with ClinicalTrials.gov and the trial identifying number is NCT02005627.
  
  
  BACKGROUND
  Primary Registry: ClinicalTrials.gov, Trial Identifying number: NCT02005627, Secondary identifying numbers: EudraCT number: 2013-003732-72 REC: 13/EM/0351, Imperial College London (Sponsor): 13IC0847, Protocol Version 6.0, Date: 16.05.2014.
authors.affiliation: Allergy and Clinical Immunology, Section Inflammation, Repair and Development, National Heart and Lung Institute (NHLI), Imperial College London, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Esther Helen
authors.initials: EH
authors.lastname: Steveling
authors.affiliation: Allergy and Clinical Immunology, Section Inflammation, Repair and Development, National Heart and Lung Institute (NHLI), Imperial College London, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Mongkol
authors.initials: M
authors.lastname: Lao-Araya
authors.affiliation: Allergy and Clinical Immunology, Section Inflammation, Repair and Development, National Heart and Lung Institute (NHLI), Imperial College London, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Koulias
authors.affiliation: Allergy and Clinical Immunology, Section Inflammation, Repair and Development, National Heart and Lung Institute (NHLI), Imperial College London, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Scadding
authors.affiliation: Allergy and Clinical Immunology, Section Inflammation, Repair and Development, National Heart and Lung Institute (NHLI), Imperial College London, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Aarif
authors.initials: A
authors.lastname: Eifan
authors.affiliation: Allergy and Clinical Immunology, Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL UK.
authors.forename: Louisa K
authors.initials: LK
authors.lastname: James
authors.affiliation: Allergy and Clinical Immunology, Section Inflammation, Repair and Development, National Heart and Lung Institute (NHLI), Imperial College London, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Alina
authors.initials: A
authors.lastname: Dumitru
authors.affiliation: Allergy and Clinical Immunology, Section Inflammation, Repair and Development, National Heart and Lung Institute (NHLI), Imperial College London, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Penagos
authors.affiliation: Allergy and Clinical Immunology, Section Inflammation, Repair and Development, National Heart and Lung Institute (NHLI), Imperial College London, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Moisés
authors.initials: M
authors.lastname: Calderón
authors.affiliation: ALK Abello, Bøge Alle 6, 2970 Hørsholm, Denmark.
authors.forename: Peter Sejer
authors.initials: PS
authors.lastname: Andersen
authors.affiliation: Allergy and Clinical Immunology, Section Inflammation, Repair and Development, National Heart and Lung Institute (NHLI), Imperial College London, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Shamji
authors.affiliation: Allergy and Clinical Immunology, Section Inflammation, Repair and Development, National Heart and Lung Institute (NHLI), Imperial College London, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
keywords: Allergic rhinitis; Allergy; CTIMP; Double-blind; GRAZAX; Hay fever; Phleum pratense; Placebo; Randomised; Sublingual immunotherapy tablet