Title: Efficacy and mechanism of low dose intradermal allergen immunotherapy in treatment of seasonal allergic rhinitis (hay fever)
Funder: Department of Health (England)

Abstract: Research design: We are proposing a phase II randomised double-blind placebo-controlled clinical trial. Study population: Adults (aged 18 years or over) with moderate-severe allergic rhinitis caused by grass pollen. Planned interventions: The active intervention will be seven two-weekly intradermal injections of grass pollen allergen at low dose (10 Biological Units; equivalent 7 ng of major allergen grass allergen Phl p 5) given before the summer grass pollen season. The control intervention will be a placebo containing histamine the dose of which will be reduced over the seven injections. Proposed outcome measures: The primary outcome will be a combined symptom and medication score for each participant as recommended by World Allergy Organization guidelines. Secondary outcomes will include separate symptom and medication scores together with a quality of life score validated for allergic rhinitis. Assessment and follow up: Clinical outcomes will be assessed during the 2013 summer grass pollen season. Proposed sample size: A power calculation for the primary outcome has been performed by the NIHR Research Design Service based on data from a trial of subcutaneous immunotherapy. This estimates that 90 subjects will give 90% power to detect a difference in the primary outcome between active and placebo treated subjects (Mann Whitney U test) with allowance for a 10% drop out rate. For this calculation the symptom and medication score improvement was conservatively estimated at 20% less than that previously reported with subcutaneous immunotherapy but still at a level considered to be clinically meaningful. Statistical analysis: Full statistical description will be analysed. For each of the variables analysed univariate descriptive statistics provide an overview of the data. Continuous variables will be presented as median and interquartile range unless otherwise stated. For categorical variables frequency counts and percentages will be presented as summary statistics for the subgroups of interest. To compare study groups we will use the Mann–Whitney U-test for continuous variables and the chi-squared test for categorical variables. The primary outcome will be analysed using the Mann-Whitney U-test between active and placebo groups. Similar analyses will be conducted for secondary (symptom scores medication scores) and mechanistic outcomes (cell counts in biopsies antibody titres). A secondary analysis based on analysis of covariance (ANCOVA) models will be also constructed to evaluate the change in quality of life scores to isolate the effect of the intervention on each arm after adjusting for any significantly different baseline characteristics between groups. Project timetables including recruitment rate: This is a 3 year study. All 90 participants will be recruited during a 5 month period. The intensive intervention and monitoring phases will last approx. 7 months. Subjects will undergo follow-up tests over the next 12 months to assess the duration of the desensitisation effect. Skin biopsies and blood samples will be collected for mechanistic investigations performed during the 2nd and 3rd years of the project.


Research activity codes: 5.1 PHARMACEUTICALS;6.1 PHARMACEUTICALS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM