CysLT1-r Expression Following Allergen Exposure in Asthma and Allergic Rhinitis - Full Text View

Sponsored by:	Laval University
Information provided by:	Laval University
ClinicalTrials.gov Identifier:	NCT00631254

Purpose

Cysteinyl leukotrienes (CysLTs) play an important role in asthma. CysLTs exert most of their bronchoconstrictive and pro-inflammatory effects through activation of the CysLT1-r. As allergic rhinitis appears to be a predisposing factor in the development of asthma and as CysLT-receptors seem to be implicated in the first steps of asthma manifestations, we think it would be of interest to determine if the CysLT1-r is a key mediator in the progression from allergic rhinitis to asthma. We believe it would be interesting to study the expression of the CysLT1-r

Our goal is to assess baseline, as well as variations following allergen bronchoprovocations, in the expression of the CysLT1-r in mild asthmatic subjects compared with non asthmatic subjects with allergic rhinitis.

Our hypothesis is that there will be a higher baseline expression of the CysLT1-r in asthmatic subjects compared with allergic rhinitis subjects and that allergen bronchoprovocations will induce an increase in the expression of the CysLT1-r in both groups.

Condition	Intervention
Asthma Allergic Rhinitis	Procedure: Allergen challenge

MedlinePlus related topics: Asthma

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Open Label, Uncontrolled, Parallel Assignment
Official Title:	Modulation of the CysLT1-r Expression Following Allergen Exposure in Non Asthmatic Subjects With Allergic Rhinitis and Mild Allergic Asthmatic Subjects Using the Induced Sputum Technique.

Further study details as provided by Laval University:

Primary Outcome Measures:

Change in CysLT1-r following allergen challenge [ Time Frame: At 7h and 24h following conventional challenge ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in CysLT1-r following low dose allergen challenge [ Time Frame: At 2 and 4 days of challenge ] [ Designated as safety issue: No ]
Difference in CysLT1-r expression in asthma and allergic rhinitis [ Time Frame: At baseline ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	October 2003
Estimated Study Completion Date:	January 2009
Estimated Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Conventional allergen challenge: increasing allergen doses given by nebulisation through the mouth and stopped when a 20% fall in forced expiratory volume in one second is obtained. Low dose allergen challenge: very low allergen doses given by nebulisation through the mouth. No more than a 5% fall in forced expiratory volume in one second. Nasal allergen challenge: One drop of increasing allergen doses on nasal mucosa.	Procedure: Allergen challenge Conventional allergen challenge: increasing allergen doses given by nebulisation through the mouth and stopped when a 20% fall in forced expiratory volume in one second is obtained. Low dose allergen challenge: very low allergen doses given by nebulisation through the mouth. No more than a 5% fall in forced expiratory volume in one second. Nasal allergen challenge: One drop of increasing allergen doses on nasal mucosa.
2: Active Comparator Low dose allergen challenge: very low allergen doses given by nebulisation through the mouth. No more than a 5% fall in forced expiratory volume in one second. Nasal allergen challenge: One drop of increasing allergen doses on nasal mucosa.	Procedure: Allergen challenge Low dose allergen challenge: very low allergen doses given by nebulisation through the mouth. No more than a 5% fall in forced expiratory volume in one second. Nasal allergen challenge: One drop of increasing allergen doses on nasal mucosa.

Arms

Assigned Interventions

1: Active Comparator

Conventional allergen challenge: increasing allergen doses given by nebulisation through the mouth and stopped when a 20% fall in forced expiratory volume in one second is obtained.

Low dose allergen challenge: very low allergen doses given by nebulisation through the mouth. No more than a 5% fall in forced expiratory volume in one second.

Nasal allergen challenge: One drop of increasing allergen doses on nasal mucosa.

Procedure: Allergen challenge

Conventional allergen challenge: increasing allergen doses given by nebulisation through the mouth and stopped when a 20% fall in forced expiratory volume in one second is obtained.

Low dose allergen challenge: very low allergen doses given by nebulisation through the mouth. No more than a 5% fall in forced expiratory volume in one second.

Nasal allergen challenge: One drop of increasing allergen doses on nasal mucosa.

2: Active Comparator

Low dose allergen challenge: very low allergen doses given by nebulisation through the mouth. No more than a 5% fall in forced expiratory volume in one second.

Nasal allergen challenge: One drop of increasing allergen doses on nasal mucosa.

Procedure: Allergen challenge

Low dose allergen challenge: very low allergen doses given by nebulisation through the mouth. No more than a 5% fall in forced expiratory volume in one second.

Nasal allergen challenge: One drop of increasing allergen doses on nasal mucosa.

Detailed Description:

We will recruit mild allergic asthmatic subjects and non asthmatic subjects with allergic rhinitis. On a baseline visit, allergy skin prick tests, spirometry, methacholine bronchoprovocation and induced sputum (IS) with differential leukocyte count will be obtained.

In a second step, mild asthmatic subjects will undergo conventional bronchial allergen challenge. IS will be obtained at 6h (corresponding to the late asthmatic response) and 24h following the challenge. The rhinitic subjects and asthmatic subjects will undergo a 4-day low dose allergen bronchial challenge as well as a nasal allergen challenge. Sputum samples will be obtained following days 2 and 4 of the low dose challenge and one week later, and 24h following nasal challenge.

Induced sputum will be analyzed for differential cell count. Total mRNA will be extracted from IS cells and used for RT-PCR.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

To have a positive reaction to one or more allergen on prick tests.
Non smokers
No respiratory track infection for at least one month prior to the study.
Asthmatic subjects using only inhaled beta-2 agonists on an as needed basis for their asthma treatment.
Asthmatic subjects with a history of asthma of at least 6 months.
Asthmatic subjects with PC20 methacholine lower or equal to 8 mg/ml.
Allergic rhinitic subjects never experienced any asthma symptoms or took any asthma medication in the past.
Allergic rhinitic subjects with a PC20 methacholine higher than 16 mg/ml.

Exclusion Criteria:

Smokers or ex smokers less than 6 months or more than 10 pack-years.
Asthmatic subjects using or used in the past 3 months inhaled or oral corticosteroids.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00631254

Contacts

Contact: Marie-Eve Boulay, MSc	418-656-8711 ext 2617	Marie-Eve.Boulay@crhl.ulaval.ca
Contact: Philippe Prince, MSc	418-656-8711 ext 2672	Philippe.Prince@crhl.ulaval.ca

Locations

Canada
Centre de recherche de l'Hopital Laval	Recruiting
Quebec, Canada, G1V 4G5

Sponsors and Collaborators

Laval University

Investigators

Principal Investigator:

Louis-Philippe Boulet, MD

Hopital Laval

More Information

Responsible Party:	Laval Hospital ( Louis-Philippe Boulet )
Study ID Numbers:	P1179
Study First Received:	February 27, 2008
Last Updated:	May 7, 2008
ClinicalTrials.gov Identifier:	NCT00631254
Health Authority:	Canada: Canadian Institutes of Health Research

Study placed in the following topic categories:

Hypersensitivity
Lung Diseases, Obstructive
Otorhinolaryngologic Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

Lung Diseases
Hypersensitivity, Immediate
Asthma
Rhinitis
Respiratory Hypersensitivity

Additional relevant MeSH terms:

Immune System Diseases
Bronchial Diseases
Nose Diseases

ClinicalTrials.gov processed this record on January 15, 2009