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Preventing Tolerance to Oxymetazoline in Allergic Rhinitis

This study has been withdrawn prior to enrollment.
(The suppliers were unable to provide the investigational medicinal product (IMP))
Sponsor:
Information provided by (Responsible Party):
Brian J Lipworth, University of Dundee
ClinicalTrials.gov Identifier:
NCT00846326
First received: February 17, 2009
Last updated: October 24, 2016
Last verified: October 2016
  Purpose
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 Intervention Phase
Allergic Rhinitis
Tachyphylaxis
Rhinitis Medicamentosa
Drug: oxymetazoline-fluticasone propionate
Drug: Oxymetazoline
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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.

Resource links provided by NLM:


Further study details as provided by University of Dundee:

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] [ Time Frame: Pre dose response, after 25, 50, 100, 200 mg/ml of oxymetazoline nasal spray ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Active Anterior Rhinomanometry [ Time Frame: Pre dose response, after 25, 50, 100, 200 mg/ml of oxymetazoline nasal spray ] [ Designated as safety issue: No ]
  • Laser Doppler Velocimetry for nasal blood flow [ Time Frame: Pre dose response, after 50 mg/ml Oxymetazoline and after 200 mg/ml of Oxymetazoline ] [ Designated as safety issue: No ]
  • Overnight urinary cortisol creatinine ratio [ Time Frame: post run-in,2 weeks, 4 weeks ] [ Designated as safety issue: Yes ]
  • Nasal nitric oxide levels [ Time Frame: after run-in, 2 weeks, 4 weeks ] [ Designated as safety issue: No ]
  • Serum eosinophils, ECP [ Time Frame: post run-in, 2 weeks, 4 weeks ] [ Designated as safety issue: No ]

Enrollment: 0
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00846326

Locations
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
Investigators
Principal Investigator: Brian Lipworth, MD, FRCP University of Dundee
  More Information

Publications:

Responsible Party: Brian J Lipworth, Professor (Clinical) Airway allergy and COPD, University of Dundee
ClinicalTrials.gov Identifier: NCT00846326     History of Changes
Other Study ID Numbers: VAI01 
Study First Received: February 17, 2009
Last Updated: October 24, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Dundee:
allergic rhinitis
rhinitis medicamentosa
imidazolines
corticosteroid

Additional relevant MeSH terms:
Rhinitis
Rhinitis, Allergic
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Oxymetazoline
Phenylephrine
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
Sympathomimetics
Nasal Decongestants
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on December 07, 2016