Preventing Tolerance to Oxymetazoline in Allergic Rhinitis

NCT00846326 | Withdrawn Phase 4

• 1 other identifier: VAI01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

The investigators wish to evaluate the effects of decongestants like oxymetazoline and the lessening of this effect with time called 'tolerance'. The investigators will demonstrate a reversal of this tolerance with nasal steroids i.e. the investigators will show that nasal steroids protect against tolerance. This will tell us more on how the investigators can make this treatment effective and safe for patients suffering with allergic rhinitis.

Conditions

Allergic Rhinitis; Tachyphylaxis; Rhinitis Medicamentosa

Keywords

allergic rhinitis; rhinitis medicamentosa; imidazolines; corticosteroid

Outcome Measures

Primary Outcomes (1)

• The primary endpoint will be the difference in peak PNIF response to incremental doses of Oxymetazoline [i.e. as a dose response]

  Pre dose response, after 25, 50, 100, 200 mg/ml of oxymetazoline nasal spray

Secondary Outcomes (5)

• Active Anterior Rhinomanometry

  Pre dose response, after 25, 50, 100, 200 mg/ml of oxymetazoline nasal spray

• Laser Doppler Velocimetry for nasal blood flow

  Pre dose response, after 50 mg/ml Oxymetazoline and after 200 mg/ml of Oxymetazoline

• Overnight urinary cortisol creatinine ratio

  post run-in,2 weeks, 4 weeks

• Nasal nitric oxide levels

  after run-in, 2 weeks, 4 weeks

• Serum eosinophils, ECP

  post run-in, 2 weeks, 4 weeks

Study Arms (2)

Oxymetazoline-Fluticasone Propionate

EXPERIMENTAL

Combination nasal spray with oxymetazoline 0.05% and fluticasone propionate 0.05%

Drug: oxymetazoline-fluticasone propionate

Oxymetazoline-placebo

PLACEBO COMPARATOR

oxymetazoline 0.05% w/v and placebo fluticasone propionate

Drug: Oxymetazoline

Interventions

oxymetazoline-fluticasone propionate DRUG

Oxymetazoline 0.05% w/v Fluticasone propionate 0.05% w/w 2 squirts in each nostril twice daily

Oxymetazoline-Fluticasone Propionate

Oxymetazoline DRUG

oxymetazoline 0.05% w/v and placebo nasal spray 2 squirts in each nostril twice daily

Oxymetazoline-placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male of Female aged 18-65 years.
• Persistent allergic rhinitis with or without asthma.
• Atopy to atleast one allergen on SPT.
• PNIF \< 120 L/min (best of 3) and reversibility with OXY \>20L/min.
• Ability to give a written informed consent.
• Ability and willingness to comply with the requirements of the protocol.

You may not qualify if:

• Recent respiratory tract/sinus infection within the last 2 months. .
• Pregnancy, planned pregnancy or lactation.
• Known or suspected hypersensitivity to any of the IMP's.
• Concomitant use of medicines (prescribed, OTC or herbal) like alpha blockers that may interfere with the trial.
• Nasal Polyposis grade 2+, Deviated nasal septum ≥ 50%
• The use of oral corticosteroids within the last 3 months.

Sponsors & Collaborators

• Brian J Lipworth: lead

Study Sites (2)

Ninewells Hospital and Medical School (Tayside NHS Trust, University of Dundee)

Dundee, DD1 9SY, United Kingdom

Location

Perth Royal Infirmary (Tayside NHS Trust)

Perth, PH1 1NX, United Kingdom

Location

Related Publications (15)

• 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.

  PMID: 11707753 BACKGROUND

• Nassef M, Shapiro G, Casale TB; Respiratory and Allergic Disease Foundation. Identifying and managing rhinitis and its subtypes: allergic and nonallergic components--a consensus report and materials from the Respiratory and Allergic Disease Foundation. Curr Med Res Opin. 2006 Dec;22(12):2541-8. doi: 10.1185/030079906x158057.

  PMID: 17265594 BACKGROUND

• Nolte H, Nepper-Christensen S, Backer V. Unawareness and undertreatment of asthma and allergic rhinitis in a general population. Respir Med. 2006 Feb;100(2):354-62. doi: 10.1016/j.rmed.2005.05.012. Epub 2005 Jul 11.

  PMID: 16005621 BACKGROUND

• Gupta R, Sheikh A, Strachan DP, Anderson HR. Burden of allergic disease in the UK: secondary analyses of national databases. Clin Exp Allergy. 2004 Apr;34(4):520-6. doi: 10.1111/j.1365-2222.2004.1935.x.

  PMID: 15080802 BACKGROUND

• Ferguson BJ. Influences of allergic rhinitis on sleep. Otolaryngol Head Neck Surg. 2004 May;130(5):617-29. doi: 10.1016/j.otohns.2004.02.001.

  PMID: 15138430 BACKGROUND

• Patou J, De Smedt H, van Cauwenberge P, Bachert C. Pathophysiology of nasal obstruction and meta-analysis of early and late effects of levocetirizine. Clin Exp Allergy. 2006 Aug;36(8):972-81. doi: 10.1111/j.1365-2222.2006.02544.x.

  PMID: 16911353 BACKGROUND

• Graf P. Long-term use of oxy- and xylometazoline nasal sprays induces rebound swelling, tolerance, and nasal hyperreactivity. Rhinology. 1996 Mar;34(1):9-13.

  PMID: 8739860 BACKGROUND

• Ramey JT, Bailen E, Lockey RF. Rhinitis medicamentosa. J Investig Allergol Clin Immunol. 2006;16(3):148-55.

  PMID: 16784007 BACKGROUND

• Petruson B. Treatment with xylometazoline (Otrivin) nosedrops over a six-week period. Rhinology. 1981 Sep;19(3):167-72.

  PMID: 6171024 BACKGROUND

• Yoo JK, Seikaly H, Calhoun KH. Extended use of topical nasal decongestants. Laryngoscope. 1997 Jan;107(1):40-3. doi: 10.1097/00005537-199701000-00010.

  PMID: 9001263 BACKGROUND

• Watanabe H, Foo TH, Djazaeri B, Duncombe P, Mackay IS, Durham SR. Oxymetazoline nasal spray three times daily for four weeks in normal subjects is not associated with rebound congestion or tachyphylaxis. Rhinology. 2003 Sep;41(3):167-74.

  PMID: 14579657 BACKGROUND

• Hallen H, Enerdal J, Graf P. Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa. Clin Exp Allergy. 1997 May;27(5):552-8.

  PMID: 9179430 BACKGROUND

• Tan KS, Grove A, McLean A, Gnosspelius Y, Hall IP, Lipworth BJ. Systemic corticosteriod rapidly reverses bronchodilator subsensitivity induced by formoterol in asthmatic patients. Am J Respir Crit Care Med. 1997 Jul;156(1):28-35. doi: 10.1164/ajrccm.156.1.9610113.

  PMID: 9230722 BACKGROUND

• Hamamdzic D, Duzic E, Sherlock JD, Lanier SM. Regulation of alpha 2-adrenergic receptor expression and signaling in pancreatic beta-cells. Am J Physiol. 1995 Jul;269(1 Pt 1):E162-71. doi: 10.1152/ajpendo.1995.269.1.E162.

  PMID: 7631772 BACKGROUND

• Davies AO, Lefkowitz RJ. Regulation of beta-adrenergic receptors by steroid hormones. Annu Rev Physiol. 1984;46:119-30. doi: 10.1146/annurev.ph.46.030184.001003. No abstract available.

  PMID: 6324653 BACKGROUND

MeSH Terms

Conditions

Rhinitis, Allergic

Interventions

Oxymetazoline

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Brian Lipworth, MD, FRCP

  University of Dundee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor (Clinical) Airway allergy and COPD

Study Record Dates

• First Submitted: February 17, 2009
• First Posted: February 18, 2009
• Last Updated: October 25, 2016

Record last verified: 2016-10

Locations

GB (2)