JAB02 Allopurinol as a novel anti-inflammatory treatment for Asthma
Research type
Research Study
Full title
JAB02 Repurposing allopurinol as a novel anti-inflammatory treatment for persistent allergic asthma.
IRAS ID
198671
Contact name
Sunny Jabbal
Contact email
Sponsor organisation
University of Dundee
Eudract number
2016-000164-42
Duration of Study in the UK
2 years, 0 months, 3 days
Research summary
We are investigating whether allopurinol has an anti-inflammatory effect in allergic asthma. Allergic asthma occurs due to an inflammatory cascade.
When exposed to antigens (allergens such as house dust mite) T-Helper-2 (TH2) cells are responsible for production of immunoglobulin E (IgE), this immunoglobulin goes on to produce downstream inflammatory processes, namely histamine and leukotrienes. Current therapies suppress these downstream responses, i.e. antihistamines, leukotriene receptor blockers (e.g. montelukast), anti IgE therapy (omalizumab).
We believe that blocking the very start of this inflammatory cascade will be more effective than blocking parts of it downstream. Based on existing research in cells and animals, we believe that allopurinol modifies the upstream TH2 cell allergic response. This is because it blocks uric acid production. Uric acid has been shown to promote the TH2 response. By reducing activation of these TH2 cells allergic asthma patients may achieve better control of symptoms, improvements in markers of inflammation in the blood, improved pulmonary function, and airway hyper-responsiveness (twitchiness/reactivity). We will measure each of these categories as outcomes in our study.
We chose airway hyper-responsiveness as our primary outcome as it closely related to the degree of allergen sensitisation. By giving an agent (mannitol) to provoke a TH2 response, we hope to show that the treated group (on allopurinol) is less hyper-responsive (reactive) to the mannitol than the control group, who are not on allopurinol. This challenge is well validated in other asthma studies, it is non-invasive and well tolerated. As far as we have read, no prior study has been done to test the hypothesis that allopurinol confers an anti-inflammatory benefit to allergic asthma. Therefore we believe our study satisfies an unmet clinical need.REC name
East of Scotland Research Ethics Service REC 2
REC reference
16/ES/0037
Date of REC Opinion
5 May 2016
REC opinion
Further Information Favourable Opinion