Differential Adrenoreceptor Mediated Tachyphylaxis and Upregulation

NCT00487032 | Completed Phase 4

• 2 other identifiers: VAI032007-003194-82
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Allergic Rhinitis; Tachyphylaxis; Rhinitis Medicamentosa

Keywords

allergic rhinitis; rhinitis medicamentosa; imidazolines; corticosteroid

Outcome Measures

Primary Outcomes (1)

• The primary endpoint will be the difference in peak PNIF response to incremental doses of Oxymetazoline [i.e. as a dose response]

  1 hour

Secondary Outcomes (4)

• Active Anterior Rhinomanometry

  1 hour

• Nasal oscillometric indices

  1 hour

• Laser Doppler Flowmetry to measure nasal blood flow

  1 hour

• Systolic, Diastolic blood pressure(measure of alpha blockade)

  1 hour

Study Arms (2)

1

EXPERIMENTAL

Prazosin 1mg challenge to block alpha 1 adrenoreceptors

Drug: Oxymetazoline 0.05% w/v; Drug: Fluticasone propionate 50 micrograms per actuation; Drug: Prazosin hydrochloride

2

PLACEBO COMPARATOR

Placebo to Prazosin

Drug: Placebo to Prazosin

Interventions

Oxymetazoline 0.05% w/v DRUG

2 squirts in each nostril thrice daily

1

Fluticasone propionate 50 micrograms per actuation DRUG

2 Squirts in each nostril twice daily

1

Prazosin hydrochloride DRUG

Prazosin 1mg one dose only

1

Placebo to Prazosin DRUG

Placebo 1 tablet one dose only

2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male of Female aged 18-65 years.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brian J Lipworth: lead

Study Sites (2)

Perth Royal Infirmary (Tayside NHS Trust)

Perth, Perthshire, PH1 1NX, United Kingdom

Location

Ninewells Hospital and Medical School (Tayside NHS Trust, University of Dundee)

Dundee, Tayside, DD1 9SY, United Kingdom

Location

Related Publications (32)

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• Vaidyanathan S, Williamson P, Clearie K, Khan F, Lipworth B. Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound congestion. Am J Respir Crit Care Med. 2010 Jul 1;182(1):19-24. doi: 10.1164/rccm.200911-1701OC. Epub 2010 Mar 4.

  PMID: 20203244 RESULT

• Vaidyanathan S, Williamson P, Lipworth B. Comparative evaluation of nasal blood flow and airflow in the decongestant response to oxymetazoline. Ann Allergy Asthma Immunol. 2012 Feb;108(2):77-80. doi: 10.1016/j.anai.2011.11.013.

  PMID: 22289724 DERIVED

MeSH Terms

Conditions

Rhinitis, Allergic

Interventions

Oxymetazoline; Prazosin

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sriram Vaidyanathan, MRCS, DOHNS

  University of Dundee

  PRINCIPAL INVESTIGATOR

• Brian Lipworth, MD, FRCP

  University of Dundee

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor (Clinical) Airway allergy and COPD

Study Record Dates

• First Submitted: June 14, 2007
• First Posted: June 15, 2007
• Study Start: May 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: April 12, 2019

Record last verified: 2019-04

Locations

GB (2)