Clinical trial NCT00846326: Preventing Tolerance to Oxymetazoline in Allergic Rhinitis
Official title: 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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Allergic Rhinitis
Tachyphylaxis
Rhinitis Medicamentosa
Keywords: allergic rhinitis
rhinitis medicamentosa
imidazolines
corticosteroid
Lead sponsor: University of Dundee
Sponsor class: OTHER
First posted: 2009-02-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The primary endpoint will be the difference in peak PNIF response to incremental doses of Oxymetazoline [i.e. as a dose response]
timeFrame: Pre dose response, after 25, 50, 100, 200 mg/ml of oxymetazoline nasal spray
Secondary outcomes:
measure: Active Anterior Rhinomanometry
timeFrame: Pre dose response, after 25, 50, 100, 200 mg/ml of oxymetazoline nasal spray
measure: Laser Doppler Velocimetry for nasal blood flow
timeFrame: Pre dose response, after 50 mg/ml Oxymetazoline and after 200 mg/ml of Oxymetazoline
measure: Overnight urinary cortisol creatinine ratio
timeFrame: post run-in,2 weeks, 4 weeks
measure: Nasal nitric oxide levels
timeFrame: after run-in, 2 weeks, 4 weeks
measure: Serum eosinophils, ECP
timeFrame: post run-in, 2 weeks, 4 weeks
Other outcomes:
Locations:
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School (Tayside NHS Trust, University of Dundee)
city: Perth
country: United Kingdom
facility: Perth Royal Infirmary (Tayside NHS Trust)
Study officials:
affiliation: University of Dundee
name: Brian Lipworth, MD, FRCP
role: PRINCIPAL_INVESTIGATOR
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