Preventing Tolerance to Oxymetazoline in Allergic Rhinitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00846326
Recruitment Status : Withdrawn (The suppliers were unable to provide the investigational medicinal product (IMP))
First Posted : February 18, 2009
Last Update Posted : October 25, 2016
Information provided by (Responsible Party):
Brian J Lipworth, University of Dundee

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 Type : Interventional  (Clinical Trial)
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.

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

Primary Outcome Measures :
  1. 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 ]

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

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00846326

United Kingdom
Ninewells Hospital and Medical School (Tayside NHS Trust, University of Dundee)
Dundee, United Kingdom, DD1 9SY
Perth Royal Infirmary (Tayside NHS Trust)
Perth, United Kingdom, PH1 1NX
Sponsors and Collaborators
Brian J Lipworth
Principal Investigator: Brian Lipworth, MD, FRCP University of Dundee


Responsible Party: Brian J Lipworth, Professor (Clinical) Airway allergy and COPD, University of Dundee Identifier: NCT00846326     History of Changes
Other Study ID Numbers: VAI01
First Posted: February 18, 2009    Key Record Dates
Last Update Posted: October 25, 2016
Last Verified: October 2016

Keywords provided by Brian J Lipworth, University of Dundee:
allergic rhinitis
rhinitis medicamentosa

Additional relevant MeSH terms:
Rhinitis, Allergic
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Nasal Decongestants
Vasoconstrictor Agents