Differential Adrenoreceptor Mediated Tachyphylaxis and Upregulation

This study has been completed.
Sponsor:
Information provided by:
University of Dundee
ClinicalTrials.gov Identifier:
NCT00487032
First received: June 14, 2007
Last updated: July 28, 2009
Last verified: July 2009
  Purpose

The investigators wish to evaluate the onset of tolerance to nasal decongestants like oxymetazoline (available over the counter) and the mechanism of tolerance particularly with differential effects on alpha 1 and alpha 2 adrenoreceptors on the nose. The investigators will 'tease' out by using an alpha 1 blocker called Prazosin. The investigators hypothesize that alpha 1 receptors mediate arterial constriction and this will be captured by measuring nasal blood flow. The investigators also hypothesize that alpha 2 receptors mediate venous sinusoid constriction and this the investigators will capture by airflow parameters like Peak Nasal Inspiratory Flow, Rhinomanometry, Oscillometric indices etc.


Condition Intervention Phase
Allergic Rhinitis
Tachyphylaxis
Rhinitis Medicamentosa
Drug: Oxymetazoline 0.05% w/v
Drug: Fluticasone propionate 50 micrograms per actuation
Drug: Prazosin hydrochloride
Drug: Placebo to Prazosin
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 Differential Tachyphylaxis of Alpha 1 and Alpha 2 Adrenoreceptor Mediated Decongestant Response to Oxymetazoline and Its Acute Reversal by Corticosteroid in Healthy Volunteers

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: 1 hour ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Active Anterior Rhinomanometry [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
  • Nasal oscillometric indices [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
  • Laser Doppler Flowmetry to measure nasal blood flow [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
  • Systolic, Diastolic blood pressure(measure of alpha blockade) [ Time Frame: 1 hour ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: May 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Prazosin 1mg challenge to block alpha 1 adrenoreceptors
Drug: Oxymetazoline 0.05% w/v
2 squirts in each nostril thrice daily
Drug: Fluticasone propionate 50 micrograms per actuation
2 Squirts in each nostril twice daily
Drug: Prazosin hydrochloride
Prazosin 1mg one dose only
Placebo Comparator: 2
Placebo to Prazosin
Drug: Placebo to Prazosin
Placebo 1 tablet one dose only

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male of Female aged 18-65 years.
  • Healthy volunteers with a negative history of seasonal or perennial nasal symptoms other than occasional common colds. Atopy will not preclude inclusion into the study as long as patients have no nasal symptoms.
  • Current non-smokers (ex-smokers for greater than 6 months duration with a total smoking history of less than 5 pack-years will be eligible).
  • PNIF > 100L/min (best effort of 3) and reversibility with OXY 2 squirts in each nostril (20 min reading) > 20 L/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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00487032

Locations
United Kingdom
Perth Royal Infirmary (Tayside NHS Trust)
Perth, Perthshire, United Kingdom, PH1 1NX
Ninewells Hospital and Medical School (Tayside NHS Trust, University of Dundee)
Dundee, Tayside, United Kingdom, DD1 9SY
Sponsors and Collaborators
University of Dundee
Investigators
Principal Investigator: Sriram Vaidyanathan, MRCS, DOHNS University of Dundee
Study Director: Brian Lipworth, MD, FRCP University of Dundee
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Sriram Vaidyanathan, University of Dundee
ClinicalTrials.gov Identifier: NCT00487032     History of Changes
Other Study ID Numbers: VAI03, 2007−003194−82
Study First Received: June 14, 2007
Last Updated: July 28, 2009
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
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Oxymetazoline
Phenylephrine
Prazosin
Fluticasone
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Nasal Decongestants
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Respiratory System Agents
Adrenergic alpha-1 Receptor Agonists
Cardiotonic Agents
Mydriatics
Protective Agents
Antihypertensive Agents
Adrenergic alpha-1 Receptor Antagonists

ClinicalTrials.gov processed this record on April 22, 2014