To Evaluate Adenosine Monophosphate and Allergen Challenge in Allergic Rhinitis

Summary

Allergic rhinitis is a common condition characterize by inflammation of the upper airways. Third generation antihistamines have been demonstrated effective in the treatment of this condition. Allergen challenge can be use to assess the effects of drugs in allergic rhinitis, adenosine monophosphate may also be used as a means to investigate these effects but as yet its effects have yet to be compared to allergen challenge. We intend to compare the effects of levocetirizine at a single dose of 5mg on allergen and AMP challenge compared to placebo in a double blind cross-over study. The study will include 20 patients with allergic rhinitis. Each patient will have allergen and AMP challenge on placebo and active treatment. The primary outcome variable will be the change in concentration of AMP/Allergen required to produce a 20% drop in nasal flow as manifest by peak nasal inspiratory flow. A 1 doubling dose change in concentration of challenge medium to cause a 20% drop in nasal flow will be deemed significant. We will also measure time to recovery after both challenges. AMP challenge is a safe alternative to allergen challenge and does not have the risk of anaphylaxis.

Timeline

Start

2005-11

Primary completion

2006-12

Completion

2006-12

Outcome

Mixed primary results

paper The primary end-point was the provocative concentration of AMP or allergen causing a 20% drop in the PNIF (PC(20)). PMID 19187327 ↗

paper PC(20) improvement amounted to a 1.26 (95% CI 0.16, 2.35) and 0.16 (95% CI -0.41, 0.73) doubling-dilution shifts for allergen and AMP challenges, respectively. PMID 19187327 ↗

Publications

• Background Togias A. Rhinitis and asthma: evidence for respiratory system integration. J Allergy Clin Immunol. 2003 Jun;111(6):1171-83; quiz 1184. doi: 10.1067/mai.2003.1592.
• Background Bousquet J, Van Cauwenberge P, Khaltaev N; Aria Workshop Group; World Health Organization. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001 Nov;108(5 Suppl):S147-334. doi: 10.1067/mai.2001.118891. No abstract available.
• Background Clough GF, Boutsiouki P, Church MK. Comparison of the effects of levocetirizine and loratadine on histamine-induced wheal, flare, and itch in human skin. Allergy. 2001 Oct;56(10):985-8. doi: 10.1034/j.1398-9995.2001.00204.x.
• Background Wang DY, Hanotte F, De Vos C, Clement P. Effect of cetirizine, levocetirizine, and dextrocetirizine on histamine-induced nasal response in healthy adult volunteers. Allergy. 2001 Apr;56(4):339-43. doi: 10.1034/j.1398-9995.2001.00775.x.
• Background Lee DK, Gray RD, Wilson AM, Robb FM, Soutar PC, Lipworth BJ. Single and short-term dosing effects of levocetirizine on adenosine monophosphate bronchoprovocation in atopic asthma. Br J Clin Pharmacol. 2004 Jul;58(1):34-9. doi: 10.1111/j.1365-2125.2004.02110.x.
• Background Terada N, Hamano N, Kim WJ, Hirai K, Nakajima T, Yamada H, Kawasaki H, Yamashita T, Kishi H, Nomura T, Numata T, Yoshie O, Konno A. The kinetics of allergen-induced eotaxin level in nasal lavage fluid: its key role in eosinophil recruitment in nasal mucosa. Am J Respir Crit Care Med. 2001 Aug 15;164(4):575-9. doi: 10.1164/ajrccm.164.4.2009046.
• Background Wilson AM, Sims EJ, Orr LC, Robb F, Lipworth BJ. An evaluation of short-term corticosteroid response in perennial allergic rhinitis using histamine and adenosine monophosphate nasal challenge. Br J Clin Pharmacol. 2003 Apr;55(4):354-9. doi: 10.1046/j.1365-2125.2003.01776.x.
• Results Vaidyanathan S, Nair A, Barnes ML, Meldrum K, Lipworth BJ. Effect of levocetirizine on nasal provocation testing with adenosine monophosphate compared with allergen challenge in allergic rhinitis. Clin Exp Allergy. 2009 Mar;39(3):409-16. doi: 10.1111/j.1365-2222.2008.03166.x.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Levocetirizine	Unknown	5 mg	—

Indications