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Nasal Ocular Reflexes Contribute to Eye Symptoms
This study has been completed.
Sponsors and Collaborators: University of Chicago
GlaxoSmithKline
Information provided by: University of Chicago
ClinicalTrials.gov Identifier: NCT00117832
  Purpose

Eye symptoms of tearing, redness and itching frequently occur in patients with allergic rhinitis or hayfever. The purpose of this trial is to study whether placing an allergen (a substance that causes allergies) directly in your nose can cause you to have eye symptoms as well as nasal symptoms.


Condition Intervention
Rhinitis, Allergic, Seasonal
Drug: Azelastine nasal spray

MedlinePlus related topics: Hay Fever
Drug Information available for: Azelastine Azelastine hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Diagnostic, Randomized, Open Label, Placebo Control, Crossover Assignment
Official Title: Nasal Ocular Reflexes Contribute to Eye Symptoms in Patients With Allergic Rhinitis

Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Amount of eye secretions collected on Schirmer strips following antigen challenge

Secondary Outcome Measures:
  • Amount of eye secretions collected on Schirmer strips following antigen challenge

Estimated Enrollment: 20
Study Start Date: March 2005
Study Completion Date: October 2006
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Detailed Description:

Symptoms of conjunctivitis (tearing, redness and itching) frequently occur in patients with allergic rhinitis. The pathophysiology underlying these symptoms remains to be elucidated. The symptoms probably arise via a combination of mechanisms including direct contact of natural pollen with the conjunctiva and reflex mechanisms originating in the nose.

Pollen exposure can result from direct hand transfer of pollen to the conjunctiva or, conceivably, from the forceful blowing of air, containing nasal secretions with antigen, up the nasolacrimal duct. The latter mechanism would be considered extremely unlikely because of the location of the nasolacrimal duct under the inferior turbinate (the duct's location is in an area with little pollen exposure) and the considerable force of air needed to cause reverse flow in the duct. The latter would also be true for topically applied intranasal drugs reaching the conjunctiva via the nasolacrimal duct, whereas the administration of medications to the conjunctiva frequently results in these medications reaching the nose via the nasolacrimal duct.

In support of direct contact of pollen as a source of ocular symptoms in patients with allergic rhinitis is the observation that pollen can be washed out of the conjunctiva on windy days, although the amount is 10 fold less than the amount of pollen recovered simultaneously from the nose. Additionally, beginning with Noon in the early 1900s, and subsequently shown by others, direct conjunctival challenges induce ocular symptoms. Thus, direct contact is a plausible explanation, but its relative contribution to eye symptoms in allergic rhinitis is unknown. Since topical intranasal steroids are known to reduce eye symptoms and the chance of them reaching the eye by systemic absorption or directly when administered intranasally are very slim, the investigators would postulate that direct allergen contact at the conjunctiva is a small contributor to the overall ocular symptom complex.

Reflex mechanisms within the nose have been shown to occur universally in response to nasal challenge with antigen. Nasal challenge with antigen induces a reflex in the contralateral nasal cavity, known as the nasonasal reflex. This reflex can also be initiated by nasal challenge with cold, dry air and histamine. The contralateral response to antigen, cold dry air and histamine is blocked by topical anticholinergic agents applied to the contralateral side, suggesting that the efferent limb is parasympathetically mediated. Histamine is only released on the side of challenge with antigen but oral H1 antihistamines reduce the contralateral response to unilateral nasal allergen challenge, suggesting that histamine contributes to the initiation of the reflex. The eye is richly innervated by parasympathetic nerves which enter the eye after running in conjunction with the parasympathetic input to the nasal cavity. The investigators, therefore, hypothesize that the conjunctiva will respond to nasal allergen in a manner similar to the contralateral nasal cavity.

Purpose: The investigators will study whether antigen-induced nasal reflexes cause eye symptoms. The investigators suspect that reflexes occur between the nose and the eye, and contribute substantially to eye symptoms in allergic patients during the allergy season. The investigators propose to demonstrate that nasal challenge with antigen leads to increased lacrimation.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • History of grass and/or ragweed allergic rhinitis.
  • Positive skin test to grass and/or ragweed antigen.
  • Positive response to screening nasal challenge.

Exclusion Criteria:

  • Physical signs or symptoms suggestive of renal, hepatic or cardiovascular disease.
  • Pregnant or lactating women.
  • Upper respiratory infection within 14 days of study start.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00117832

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
GlaxoSmithKline
Investigators
Principal Investigator: Robert M Naclerio, MD University of Chicago
  More Information

Publications:
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Yanez A, Rodrigo GJ. Intranasal corticosteroids versus topical H1 receptor antagonists for the treatment of allergic rhinitis: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2002 Nov;89(5):479-84. Review.
Gray RD, Haggart K, Lee DK, Cull S, Lipworth BJ. Effects of butterbur treatment in intermittent allergic rhinitis: a placebo-controlled evaluation. Ann Allergy Asthma Immunol. 2004 Jul;93(1):56-60.
Hampel F Jr, Howland W 3rd, Van Bavel J, Ratner P. A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of ebastine (20 mg and 10 mg) to loratadine 10 mg once daily in the treatment of seasonal allergic rhinitis. J Investig Allergol Clin Immunol. 2004;14(1):56-63.
Shahar E, Hassoun G, Pollack S. Effect of vitamin E supplementation on the regular treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2004 Jun;92(6):654-8.
van Adelsberg J, Philip G, Pedinoff AJ, Meltzer EO, Ratner PH, Menten J, Reiss TF; Montelukast Fall Rhinitis Study Group. Montelukast improves symptoms of seasonal allergic rhinitis over a 4-week treatment period. Allergy. 2003 Dec;58(12):1268-76. Erratum in: Allergy. 2004 Mar;59(3):357.
Remberg P, Bjork L, Hedner T, Sterner O. Characteristics, clinical effect profile and tolerability of a nasal spray preparation of Artemisia abrotanum L. for allergic rhinitis. Phytomedicine. 2004 Jan;11(1):36-42.
Kirchhoff CH, Kremer B, Haaf-von Below S, Kyrein HJ, Mosges R. Effects of dimethindene maleate nasal spray on the quality of life in seasonal allergic rhinitis. Rhinology. 2003 Sep;41(3):159-66.
Lumry W, Hampel F, LaForce C, Kiechel F, el-Akkad T, Murray JJ. A comparison of once-daily triamcinolone acetonide aqueous and twice-daily beclomethasone dipropionate aqueous nasal sprays in the treatment of seasonal allergic rhinitis. Allergy Asthma Proc. 2003 May-Jun;24(3):203-10.
van Adelsberg J, Philip G, LaForce CF, Weinstein SF, Menten J, Malice MP, Reiss TF; Montelukast Spring Rhinitis Investigator Group. Randomized controlled trial evaluating the clinical benefit of montelukast for treating spring seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2003 Feb;90(2):214-22.
Nayak AS, Philip G, Lu S, Malice MP, Reiss TF; Montelukast Fall Rhinitis Investigator Group. Efficacy and tolerability of montelukast alone or in combination with loratadine in seasonal allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled trial performed in the fall. Ann Allergy Asthma Immunol. 2002 Jun;88(6):592-600.
Wilson AM, Orr LC, Coutie WJ, Sims EJ, Lipworth BJ. A comparison of once daily fexofenadine versus the combination of montelukast plus loratadine on domiciliary nasal peak flow and symptoms in seasonal allergic rhinitis. Clin Exp Allergy. 2002 Jan;32(1):126-32.
Kilpelainen M, Terho EO, Helenius H, Koskenvuo M. Validation of a new questionnaire on asthma, allergic rhinitis, and conjunctivitis in young adults. Allergy. 2001 May;56(5):377-84.
Ratner PH, Lim JC, Georges GC. Comparison of once-daily ebastine 20 mg, ebastine 10 mg, loratadine 10 mg, and placebo in the treatment of seasonal allergic rhinitis. The Ebastine Study Group. J Allergy Clin Immunol. 2000 Jun;105(6 Pt 1):1101-7.
Van Cauwenberge P, Juniper EF. Comparison of the efficacy, safety and quality of life provided by fexofenadine hydrochloride 120 mg, loratadine 10 mg and placebo administered once daily for the treatment of seasonal allergic rhinitis. Clin Exp Allergy. 2000 Jun;30(6):891-9.
Meltzer EO, Malmstrom K, Lu S, Prenner BM, Wei LX, Weinstein SF, Wolfe JD, Reiss TF. Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: a randomized, placebo-controlled clinical trial. J Allergy Clin Immunol. 2000 May;105(5):917-22.
Hadley JA. Evaluation and management of allergic rhinitis. Med Clin North Am. 1999 Jan;83(1):13-25.
Yang WH, Dolovich J, Drouin MA, Keith P, Haddon J, Jennings B. Comparison of budesonide Turbuhaler with budesonide aqua in the treatment of seasonal allergic rhinitis. Rhinocort Study Group. Can Respir J. 1998 Nov-Dec;5(6):455-60.
Stern MA, Dahl R, Nielsen LP, Pedersen B, Schrewelius C. A comparison of aqueous suspensions of budesonide nasal spray (128 micrograms and 256 micrograms once daily) and fluticasone propionate nasal spray (200 micrograms once daily) in the treatment of adult patients with seasonal allergic rhinitis. Am J Rhinol. 1997 Jul-Aug;11(4):323-30.
Simola M, Boss I, Holopainen E, Malmberg H, Ruoppi P, Seppa J, Siivonen L, Suonpaa J, Piepponen T. Astemizole in combination with pseudoephedrine in the treatment of seasonal allergic rhinitis. Rhinology. 1996 Mar;34(1):21-3.
Pedersen B, Dahl R, Richards DH, Jacques LA, Larsen BB, Pichler W, Nykanen KN. Once daily fluticasone propionate aqueous nasal spray controls symptoms of most patients with seasonal allergic rhinitis. Allergy. 1995 Oct;50(10):794-9.
Settipane G, Korenblat PE, Winder J, Lumry W, Murphree J, Alderfer VB, Simpson B, Smith JA. Triamcinolone acetonide Aqueous nasal spray in patients with seasonal ragweed allergic rhinitis: a placebo-controlled, double-blind study. Clin Ther. 1995 Mar-Apr;17(2):252-63.
Darnell R, Pecoud A, Richards DH. A double-blind comparison of fluticasone propionate aqueous nasal spray, terfenadine tablets and placebo in the treatment of patients with seasonal allergic rhinitis to grass pollen. Clin Exp Allergy. 1994 Dec;24(12):1144-50.
Loth S, Bende M. Effect of nasal anaesthesia on lacrimal function after nasal allergen challenge. Clin Exp Allergy. 1994 Apr;24(4):375-6.
Dolovich J, O'Connor M, Stepner N, Smith A, Sharma RK. Double-blind comparison of intranasal fluticasone propionate, 200 micrograms, once daily with 200 micrograms twice daily in the treatment of patients with severe seasonal allergic rhinitis to ragweed. Ann Allergy. 1994 May;72(5):435-40.
Bousquet J, Chanal I, Alquie MC, Charpin D, Didier A, Germouty J, Greillier P, Ickovic MH, Maria Y, Montane F, et al. Prevention of pollen rhinitis symptoms: comparison of fluticasone propionate aqueous nasal spray and disodium cromoglycate aqueous nasal spray. A multicenter, double-blind, double-dummy, parallel-group study. Allergy. 1993 Jul;48(5):327-33.
Frolund L. Efficacy of an oral antihistamine, loratadine, as compared with a nasal steroid spray, beclomethasone dipropionate, in seasonal allergic rhinitis. Clin Otolaryngol Allied Sci. 1991 Dec;16(6):527-31.
Juniper EF, Guyatt GH, O'Byrne PM, Viveiros M. Aqueous beclomethasone diproprionate nasal spray: regular versus "as required" use in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol. 1990 Sep;86(3 Pt 1):380-6.
Frolund L, Etholm B, Irander K, Johannessen TA, Odkvist L, Ohlander B, Weeke B. A multicentre study of loratadine, clemastine and placebo in patients with perennial allergic rhinitis. Allergy. 1990 May;45(4):254-61.
Johansen LV, Bjerrum P, Illum P. Treatment of seasonal allergic rhinitis--a double blind, group comparative study of terfenadine and dexchlorpheniramine. Rhinology. 1987 Mar;25(1):35-40.
Borum P, Gronborg H, Mygind N. Seasonal allergic rhinitis and depot injection of a corticosteroid. Evaluation of the efficacy of medication early and late in the season based on detailed symptom recording. Allergy. 1987 Jan;42(1):26-32.
Wood SF. Oral antihistamine or nasal steroid in hay fever: a double-blind double-dummy comparative study of once daily oral astemizole vs twice daily nasal beclomethasone dipropionate. Clin Allergy. 1986 May;16(3):195-201.
Orgel HA, Meltzer EO, Kemp JP, Welch MJ. Clinical, rhinomanometric, and cytologic evaluation of seasonal allergic rhinitis treated with beclomethasone dipropionate as aqueous nasal spray or pressurized aerosol. J Allergy Clin Immunol. 1986 Jun;77(6):858-64.
Backhouse CI, Finnamore VP, Gosden CW. Treatment of seasonal allergic rhinitis with flunisolide and terfenadine. J Int Med Res. 1986;14(1):35-41.
Beswick KB, Kenyon GS, Cherry JR. A comparative study of beclomethasone dipropionate aqueous nasal spray with terfenadine tablets in seasonal allergic rhinitis. Curr Med Res Opin. 1985;9(8):560-7.
Schaaf L, Hendeles L, Weinberger M. Suppression of seasonal allergic rhinitis symptoms with daily hydroxyzine. J Allergy Clin Immunol. 1979 Feb;63(2):129-33.
Cockcroft DW, MacCormack DW, Newhouse MT, Hargreave FE. Beclomethasone dipropionate aerosol in allergic rhinitis. Can Med Assoc J. 1976 Sep 18;115(6):523-6.
Lofkvist T, Svensson G. An open assessment of becotide (beclomethasone dipropionate) nasal spray in seasonal allergic rhinitis. Acta Allergol. 1975 Oct;30(4):227-38.

Publications indexed to this study:
Study ID Numbers: 13716A
Study First Received: June 30, 2005
Last Updated: May 27, 2008
ClinicalTrials.gov Identifier: NCT00117832  
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Chicago:
allergic rhinitis

Study placed in the following topic categories:
Hypersensitivity
Otorhinolaryngologic Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Rhinitis, Allergic, Seasonal
Hypersensitivity, Immediate
Histamine phosphate
Rhinitis
Azelastine
Histamine
Respiratory Hypersensitivity

Additional relevant MeSH terms:
Respiratory System Agents
Neurotransmitter Agents
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Asthmatic Agents
Histamine Agents
Enzyme Inhibitors
Anti-Allergic Agents
Nose Diseases
Pharmacologic Actions
Lipoxygenase Inhibitors
Histamine Antagonists
Autonomic Agents
Therapeutic Uses
Histamine H1 Antagonists
Peripheral Nervous System Agents
Histamine H1 Antagonists, Non-Sedating
Bronchodilator Agents

ClinicalTrials.gov processed this record on January 14, 2009