Preventing Tolerance to Oxymetazoline in Allergic Rhinitis

October 24, 2016 updated by: Brian J Lipworth

A Proof of Concept Study to Evaluate if Concomitant Topical Intranasal Steroid Prevents Tolerance and Rebound Congestion Due to Regular Oxymetazoline in Persistent Allergic Rhinitis.

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Allergic rhinitis (AR) affects upto 25% of the worldwide population and is associated with asthma, with Scotland having the highest prevalence in the world. Nasal blockage is the main symptom of allergic rhinitis. Nasal blockage affects sleep quality and impairs daytime performance. It is a major cause of sickness absenteeism and has been shown to adversely affect quality of life. The most efficacious class of drugs for nasal blockage in AR are the nasal decongestants (sympathomimetics acting on alpha receptors which unblock the nose). These are available over the counter for routine use by people experiencing nasal blockage. Nasal steroids are the most effective drugs for overall symptoms of allergic rhinitis and are considered first line therapy by recent guidelines. There is widespread belief that prolonged use of decongestant sprays like oxymetazoline can result in a condition of decreased effectiveness called tolerance. It is thought that with time they lose their effectiveness and more and more medication is needed to achieve the same level of decongestion. Also it has been proposed that once stopped, the patient experiences rebound congestion. Long term users of nasal decongestants cannot get off their sprays because of this vicious cycle. These sprays act via stimulating the alpha adrenoreceptors in the nose. It is a poorly understood condition and the mechanism of action is unclear. What is also not clear is the time to onset of tolerance. From studies in the lung we know that tolerance in certain types of adrenoreceptors can be reversed by use of corticosteroids. We have also seen over many years of clinical practice that concomitant use of steroid sprays and decongestants prevents the onset of tolerance and rebound. Anecdotally, patients are often treated with this combination in clinic particularly during a common cold, hayfever season with high pollen counts and acute exacerbations. Therefore, we would like to conduct a proof of concept study to show that a combination nasal spray of decongestant and steroid protects against tolerance. We will also show protection against early rebound congestion. This will enable a new lease of life for allergic rhinitis sufferers, whose quality of life is most affected by nasal blockage and the absence of an effective long term drug strategy for it.

Study Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Dundee, United Kingdom, DD1 9SY
        • Ninewells Hospital and Medical School (Tayside NHS Trust, University of Dundee)
      • Perth, United Kingdom, PH1 1NX
        • Perth Royal Infirmary (Tayside NHS Trust)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oxymetazoline-Fluticasone Propionate
Combination nasal spray with oxymetazoline 0.05% and fluticasone propionate 0.05%
Drug: oxymetazoline-fluticasone propionate
Oxymetazoline 0.05% w/v Fluticasone propionate 0.05% w/w 2 squirts in each nostril twice daily
Placebo Comparator: Oxymetazoline-placebo
oxymetazoline 0.05% w/v and placebo fluticasone propionate
Drug: Oxymetazoline
oxymetazoline 0.05% w/v and placebo nasal spray 2 squirts in each nostril twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary endpoint will be the difference in peak PNIF response to incremental doses of Oxymetazoline [i.e. as a dose response]
Time Frame: Pre dose response, after 25, 50, 100, 200 mg/ml of oxymetazoline nasal spray
Pre dose response, after 25, 50, 100, 200 mg/ml of oxymetazoline nasal spray

Secondary Outcome Measures

Outcome Measure
Time Frame
Active Anterior Rhinomanometry
Time Frame: Pre dose response, after 25, 50, 100, 200 mg/ml of oxymetazoline nasal spray
Pre dose response, after 25, 50, 100, 200 mg/ml of oxymetazoline nasal spray
Laser Doppler Velocimetry for nasal blood flow
Time Frame: Pre dose response, after 50 mg/ml Oxymetazoline and after 200 mg/ml of Oxymetazoline
Pre dose response, after 50 mg/ml Oxymetazoline and after 200 mg/ml of Oxymetazoline
Overnight urinary cortisol creatinine ratio
Time Frame: post run-in,2 weeks, 4 weeks
post run-in,2 weeks, 4 weeks
Nasal nitric oxide levels
Time Frame: after run-in, 2 weeks, 4 weeks
after run-in, 2 weeks, 4 weeks
Serum eosinophils, ECP
Time Frame: post run-in, 2 weeks, 4 weeks
post run-in, 2 weeks, 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brian J Lipworth

Investigators

  • Principal Investigator: Brian Lipworth, MD, FRCP, University of Dundee

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

February 17, 2009

First Submitted That Met QC Criteria

February 17, 2009

First Posted (Estimate)

February 18, 2009

Study Record Updates

Last Update Posted (Estimate)

October 25, 2016

Last Update Submitted That Met QC Criteria

October 24, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VAI01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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