Clinical trial NCT00625989: The Effect of Allergen Inhalation on Sputum Myeloid and Plasmacytoid Dendritic Cells in Mild Atopic Asthmatics
Official title: The Effect of Allergen Inhalation on Sputum Myeloid and Plasmacytoid Dendritic Cells in Mild Atopic Asthmatics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Asthma
Keywords: asthma
atopy
allergen challenge
sputum myeloid and plasmacytoid dendritic cells
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2008-02-29
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Summary:

A picture is emerging of dendritic cells migrating through the blood to the airways following allergen inhalation in atopic asthmatics. Although the Koh and McCarthy articles present novel findings, both do not provide a comprehensive view of sputum DCs following allergen challenge. Therefore, the proposed study will examine the kinetics of mDCs and pDCs in the induced sputum of atopic asthmatics following inhalation of allergen.

Hypothesis:

Following allergen challenge, sputum myeloid and plasmacytoid DCs will migrate into the airway lumen in atopic asthmatics during the timeframe of the late asthmatic response.

Objective:

The objective of this study is to examine the kinetics of dendritic cells in induced sputum following allergen challenge in atopic asthmatic subjects.

Detailed description: Subjects will be put through two study periods. Each study period will consist of four visits and will be separated by 2-4 weeks. On the first visit, subjects will undergo screening procedures, including complete history and physical examination. In addition, methacholine inhalation challenge and skin-prick testing will be preformed to assess airway hyper-responsiveness and determine atopic status respectively. Lastly, sputum will be induced before challenge (0 hrs) and peripheral blood will be collected. On the second visit, subjects will inhale diluent or allergen and sputum will be collected 7 hours following inhalation challenge. Next, on the third visit, subjects will return 24 hours following inhalation challenge and sputum will be induced. On the final visit, subjects will return 72 hours following inhalation challenge and sputum will be collected, along with peripheral blood.

Before the next study period begins, there will be a washout period of 2-4 weeks. On the first visit of the second study period, a methacholine challenge will be performed to ensure the return of PC20 to within one doubling dose of baseline values. Also, sputum will be induced before challenge (0hrs) and peripheral blood will be collected. On the second visit, subjects will inhale diluent or allergen and sputum will be collected 7hrs following inhalation challenge. Next, on the third visit, subjects will return 24 hours following inhalation challenge and sputum will be induced. On the final visit, subjects will return 72 hours following inhalation challenge and sputum will be collected, along with peripheral blood.

Eligibility criteria: Inclusion Criteria:

* Mild atopic asthmatics, presently well controlled on ß2-agonists.
* Non-smokers.
* Baseline FEV1 more than 70% of predicted normal.

Exclusion Criteria:

* Airway infection during the last 4 weeks.
* Exacerbation during the last 4 weeks.
* Inhaled or oral steroids during the last 4 weeks.
* Antihistamines during the last 48 hours.
* Asthma medication other than inhaled and/or oral ß2-agonists during the last 4 weeks.
* Pregnant women.

Primary outcomes:
measure: The Primary Outcome Measure for This Study is the Number of Sputum Myeloid Dendritic Cells
timeFrame: 24 hrs
measure: The Primary Outcome Measure for This Study is the Number of Sputum Plasmacytoid Dendritic Cells
timeFrame: 24 hrs
Secondary outcomes:
measure: The Secondary Outcome Measure is the Level of Specific Chemokines Released in the Sputum Supernatant.
timeFrame: Before inhalation (0hrs)
measure: The Secondary Outcome Measure is the Level of Specific Chemokines Released in the Sputum Supernatant
timeFrame: 7 hrs
measure: The Secondary Outcome Measure is the Level of Specific Chemokines Released in the Sputum Supernatant
timeFrame: 24 hrs
measure: The Secondary Outcome Measure is the Level of Specific Chemokines Released in the Sputum Supernatant
timeFrame: 72 hrs
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
Study officials:
affiliation: McMaster University
name: Paul O'Byrne, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Gail Gauvreau, PhD
role: PRINCIPAL_INVESTIGATOR
References: