Detection of Cav1 Calcium Channels in Inflammatory Cells of Asthmatic Children (CAVASTHME)

Asthma affects about 10% of children and 6% of adults in industrialized countries. Lymphocytes (L) Th2, a T cell population (LT) producing interleukin (IL) -4, 5 and 13 are broadly involved in this pathology in experimental models and in humans. Many studies show that the signaling pathways activated by the commitment of T receiver differ depending LT. The identification of specific signaling pathways links to Th2 offer new therapeutic approaches. Precedent study showed that mouse Th2 selectively expressed related to calcium channels sensitive channels Cav1 voltage, normally found in excitable cells where they are defined as receivers dihydropyridine (DHP).

The goal of the present study is to show the presence of Cav1 channels in inflammatory cells in allergic asthmatics and show overexpression of these channels in the peripheral blood mononuclear cells from asthmatic subjects before and / or after stimulation with the TCR in comparison with controls.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Procedure: Induced sputum method using hypertonic serum

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

For Asthmatic children arm :

• Girl not in childbearing potential or taking contraceptive treatment
• Asthma diagnosis in at least 6 months as defined by clinical symptoms (expiratory dyspnea, wheezing, sibilance) and respiratory function (reversibility of VEMS at least 12% after salbutamol administration)
• Allergologic tests positives to airborne allergens : positive prick test and/or specific IgE > 0,35 kU/L for at least one allergen
• Asthma severity between mild to moderate based on Global initiative for asthma classification during more than one month with inhaled corticotherapies +/- long term action beta -mimetic long compounds (salmeterol, formoterol)
• Patient insured with a social security scheme

For control children arm :

• Girl not in childbearing potential or taking contraceptive treatment
• No medical history of asthma
• No medical history of allergy or symptoms of allergy on skin (atopic dermatitis), respiratory tract (rhino-conjunctivitis, asthma) or food allergy

Exclusion Criteria:

For both arms:

• Chronic respiratory pathology : known occlusive or restrictive respiratory syndrome like interstitial lung disease, neuromuscular disease, mucoviscidoses, respiratory tract abnormalities with cough, dyspnea or digital hippocratism.
• History of pulmonary or nose and throat infectious disease during last 4 months
• Parasitic disease non treated during last 3 months
• Dyspnea during the inclusion
• Systemic corticotherapy during the last 3 months before inclusion
• Immunosuppressive therapy during the last 3 months before inclusion
• Diabeta
• Disease causing immune disorder
• Infection during inclusion
• Participation to another study witch implies medical treatment during last 3 months before inclusion

For asthmatic children arm :

• Chronic pulmonary pathology (excluding asthma)
• Asthma exacerbation during inclusion
• VEMS < 70% of normal range or VEMS < 70% of normal range after inhalation of serum (despite salbutamol administration)
• Patient unable to complete pulmonary function testing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Asthmatic children; Induced sputum method using hypertonic serum	Procedure: Induced sputum method using hypertonic serum; Collection of expectoration in sterile vial, conserved in ice all along the examination
Sham Comparator: Control children; Induced sputum method using hypertonic serum	Procedure: Induced sputum method using hypertonic serum; Collection of expectoration in sterile vial, conserved in ice all along the examination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Detection of sequence coding for Cav1 in cells as assessed by reverse transcription polymerase chain reaction	Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Presence of Cav1 channels as assessed by correlation between Cav1 expression and eosinophils in expectoration collection	Day 1
Presence of Cav1 channels as assessed by correlation between Cav1 expression and lymphocytes T in expectoration collection	Day 1
Comparison of CRTH2+ cells in total blood between asthmatic and control group	Day 1
Comparison of Cav1 channels and cytokines Th2 expression between asthmatic and control group before T-Cell receptor stimulation	Day 1
Comparison of Cav1 channels and cytokines Th2 expression between asthmatic and control group after T-Cell receptor stimulation	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: François Brémont, MD, Hôpital des Enfants CHU Toulouse

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: May 17, 2016
• First Submitted That Met QC Criteria: June 17, 2016
• First Posted (Estimate): June 22, 2016

Study Record Updates

• Last Update Posted (Estimate): June 22, 2016
• Last Update Submitted That Met QC Criteria: June 17, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Lymphocytes Th2; Cav1 channels
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 11 054 03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO