Trial of Verapamil in Chronic Rhinosinusitis

Summary

Verapamil is an L-type calcium channel blocker(CCB) which has been shown to reduce inflammation in a variety of tissues. Verapamil has also been shown to improve eosinophilic inflammation in an animal model of asthma and also functions as a P-glycoprotein(P-gp) inhibitor. A major subtype of chronic rhinosinusitis(CRS) is characterized by eosinophilic inflammation as well as P-gp overexpression. The goal of this study is to therefore see whether Verapamil may be used to treat CRS.

Timeline

Start

2015-05

Primary completion

2016-03

Completion

2017-05

Publications

• Background Chin D, Harvey RJ. Nasal polyposis: an inflammatory condition requiring effective anti-inflammatory treatment. Curr Opin Otolaryngol Head Neck Surg. 2013 Feb;21(1):23-30. doi: 10.1097/MOO.0b013e32835bc3f9.
• Background Poetker DM, Jakubowski LA, Lal D, Hwang PH, Wright ED, Smith TL. Oral corticosteroids in the management of adult chronic rhinosinusitis with and without nasal polyps: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013 Feb;3(2):104-20. doi: 10.1002/alr.21072. Epub 2012 Aug 7.
• Background Khakzad MR, Mirsadraee M, Mohammadpour A, Ghafarzadegan K, Hadi R, Saghari M, Meshkat M. Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals. Pulm Pharmacol Ther. 2012 Apr;25(2):163-8. doi: 10.1016/j.pupt.2011.11.001. Epub 2011 Nov 25.
• Background Matsumori A, Nishio R, Nose Y. Calcium channel blockers differentially modulate cytokine production by peripheral blood mononuclear cells. Circ J. 2010 Mar;74(3):567-71. doi: 10.1253/circj.cj-09-0467. Epub 2010 Jan 30.
• Background Hashioka S, Klegeris A, McGeer PL. Inhibition of human astrocyte and microglia neurotoxicity by calcium channel blockers. Neuropharmacology. 2012 Sep;63(4):685-91. doi: 10.1016/j.neuropharm.2012.05.033. Epub 2012 May 30.
• Background Li G, Qi XP, Wu XY, Liu FK, Xu Z, Chen C, Yang XD, Sun Z, Li JS. Verapamil modulates LPS-induced cytokine production via inhibition of NF-kappa B activation in the liver. Inflamm Res. 2006 Mar;55(3):108-13. doi: 10.1007/s00011-005-0060-y.
• Background Bacon KB, Westwick J, Camp RD. Potent and specific inhibition of IL-8-, IL-1 alpha- and IL-1 beta-induced in vitro human lymphocyte migration by calcium channel antagonists. Biochem Biophys Res Commun. 1989 Nov 30;165(1):349-54. doi: 10.1016/0006-291x(89)91076-0.
• Background Becker WJ. Cluster headache: conventional pharmacological management. Headache. 2013 Jul-Aug;53(7):1191-6. doi: 10.1111/head.12145. Epub 2013 Jun 14.
• Background Cohen AS, Matharu MS, Goadsby PJ. Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy. Neurology. 2007 Aug 14;69(7):668-75. doi: 10.1212/01.wnl.0000267319.18123.d3.
• Background Lanteri-Minet M, Silhol F, Piano V, Donnet A. Cardiac safety in cluster headache patients using the very high dose of verapamil (>/=720 mg/day). J Headache Pain. 2011 Apr;12(2):173-6. doi: 10.1007/s10194-010-0289-x. Epub 2011 Jan 22.
• Background Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl. 2012 Mar;23:3 p preceding table of contents, 1-298.
• Background Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009 Oct;34(5):447-54. doi: 10.1111/j.1749-4486.2009.01995.x.

Drugs

Indications