NCT02806466

Brief Summary

  • Background: Asthma is a frequent disease characterized by bronchial hyperresponsiveness, inflammation and remodeling. Consistent epidemiological data indicate that outcome of asthma in adults may be determined in early childhood. This may be due to bronchial remodeling, an abnormal repair process that contributes to the development of poorly reversible airway narrowing. It appears very early in the natural history of the disease and involves increased mass of bronchial smooth muscle (BSM). The mechanism of such an increase has been related with an increase in smooth muscle cell proliferation. Recently, we have demonstrated that in severe asthma, BSM increased proliferation is induced by an enhanced mitochondrial biogenesis. Moreover, we have also shown that immature human, non-asthmatic airway smooth muscle cells (ASMC) proliferate to a greater extent than normal adult ASMC, in a similar fashion to adult asthmatic ASMC. Immature ASMC may thus have great potential to stimulate airway remodeling. We thus hypothesized that remodeling is an early process and certain characteristics of ASMC in severe preschool asthma may predispose such children to persistent remodeling with airway obstruction later in life.
  • Purpose: To investigate prognostic factors of airway remodeling in preschool children, with special attention to ASMC proliferation (mitochondrial mass \& biogenesis).
  • Methods: In the initial phase of the project, 75 severe asthmatic preschool children (\<5 yr) will be prospectively recruited from the "CHU de Bordeaux" and the "CHU de Toulouse" according to the "Haute Autorité de Santé" criteria. Inclusion visit will include written informed consent, asthma control evaluation, clinical examination, lung function testing (exhaled NO, plethysmography), prick tests, chest X Ray and blood sample for total IgE levels. Bronchial specimens from all subjects will be obtained by fiberoptic bronchoscopy at visit 2. Airway remodeling will be evaluated by morphological analysis. After smooth muscle mitochondria will be analyzed by electronic microscopy \& immunoblotting. Comparison between the 2 groups will be performed by unpaired t tests for parametric data and x2-tests for non-parametric data. In the second phase of the project, patients will then be followed-up till the age of 7-10 yrs, when another bronchoscopy with biopsies will be performed.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
67

participants targeted

Target at P25-P50 for not_applicable asthma

Timeline
Completed

Started Mar 2012

Longer than P75 for not_applicable asthma

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2012

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2015

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

June 15, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 20, 2016

Completed
Last Updated

June 20, 2016

Status Verified

June 1, 2016

Enrollment Period

3.7 years

First QC Date

June 15, 2016

Last Update Submit

June 15, 2016

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

  • Evaluation of Airway remodeling (distance from the reticular membrane to the smooth muscle).

    1 day

Study Arms (2)

Asthmatic children

ACTIVE COMPARATOR
Procedure: Fiberoptic bronchoscopy

Non-asthmatic children

SHAM COMPARATOR
Procedure: Fiberoptic bronchoscopy

Interventions

Fiberoptic bronchoscopyPROCEDURE
Asthmatic childrenNon-asthmatic children

Eligibility Criteria

Age1 Year - 5 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Asthmatic children
  • Parents (and possibly the child) who gave written informed consent.
  • Affiliated with a social security scheme.
  • Age from 1 to less than 5 years.
  • Severe persistent asthma according to the criteria of the National Health Authority (Annex I) or NEW PROPOSED CRITERIA (adapted ATS (42)):
  • Major criteria (\> 1) Asthma control in mild to moderate level requiring
  • A continuous or semi continuous (≥ 50% of the year) by oral corticosteroids
  • A treatment with high doses of inhaled corticosteroids (\> 500 micrograms / day of Beclomethasone, or equivalent (\> 400 micrograms / day of Budesonide,\> 200 micrograms / day of Fluticasone) for at least 6 weeks.
  • And
  • minor criteria (\> 2)
  • The need for an additional daily treatment (β2-agonists, long-acting, theophylline, anti-leukotrienes)
  • Symptoms that require taking daily or almost daily of β2-agonists of short action
  • persistent obstruction (FEV \<80% PEF variability\> 20%) (If reliable spirometry, usually\> 5 years of age)
  • One or more seeking care in emergency / year
  • At least three short courses of oral corticosteroids / year
  • +15 more criteria

You may not qualify if:

  • Asthmatic children:
  • Subject with significant co-morbidity associated with asthma not of any nature whatsoever
  • Subject with a dental infection, or nasopharyngeal airway (viral or bacterial) with fever (\> 39 ° C) in the 4 weeks preceding the survey.
  • chronic viral infections (hepatitis, HIV).
  • Review of hemostasis abnormal,
  • Subject with a heart condition,
  • Subject is not fasted for over 6 hours.
  • Children without asthma:
  • Non-asthmatic children with indication of endoscopy:
  • asthma diagnosed by a doctor.
  • Subject with significant co-morbidity associated with asthma not of any nature whatsoever.
  • Subject with a dental infection, or nasopharyngeal airway (viral or bacterial) with fever (\> 39 ° C) in the 4 weeks preceding the survey.
  • chronic viral infections (hepatitis, HIV).
  • Review of hemostasis abnormal,
  • Subject with a heart condition,
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

CHU de Bordeaux

Bordeaux, Aquitaine, 33000, France

Location

Hôpital des Enfants

Toulouse, Occitanie, 31026, France

Location

Related Publications (1)

  • Fayon M, Beaufils F, Esteves P, Campagnac M, Maurat E, Michelet M, Siao-Him-Fa V, Lavrand F, Simon G, Begueret H, Berger P; P'tit Asthme Study Group. Bronchial Remodeling-based Latent Class Analysis Predicts Exacerbations in Severe Preschool Wheezers. Am J Respir Crit Care Med. 2023 Feb 15;207(4):416-426. doi: 10.1164/rccm.202205-0913OC.

    PMID: 36108144DERIVED

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Study Officials

  • MICHAEL FAYON, Professor

    University Hospital, Bordeaux

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 15, 2016

First Posted

June 20, 2016

Study Start

March 1, 2012

Primary Completion

November 1, 2015

Study Completion

November 1, 2015

Last Updated

June 20, 2016

Record last verified: 2016-06

Data Sharing

IPD Sharing
Will not share

Locations

FR(2)