Preventing Tolerance to Oxymetazoline in Allergic Rhinitis

Sponsor

Brian J Lipworth (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00846326

Collaborator

(none)

Enrollment

Locations

Arms

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Allergic Rhinitis Tachyphylaxis Rhinitis Medicamentosa	Drug: oxymetazoline-fluticasone propionate Drug: Oxymetazoline	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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.

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ninewells Hospital and Medical School (Tayside NHS Trust, University of Dundee)	Dundee		United Kingdom	DD1 9SY
2	Perth Royal Infirmary (Tayside NHS Trust)	Perth		United Kingdom	PH1 1NX