Study of Dose-response to Bronchodilator and Dose-finding in Child 2.5 to 6 Years - Study Golden (DORESI)

February 3, 2023 updated by: Assistance Publique - Hôpitaux de Paris

Study on Dose-response to Bronchodilator Then Bronchodilator Dose-finding Using the Flow Interruption Technique in Children Aged 2.5 TO 6 Years

In older children and adults, bronchodilator (BD) dose-effect relationship is part of the characteristics of asthma disease. There are no data on BD dose-response relationship in wheezy preschool children whose disease pathophysiology is poorly understood, but may, in part, takes on the characteristics of asthma.

The investigators assume that 1) in young children interrupter resistance (Rint) could be used to measure a BD effect 2) the response to BD may vary depending on the dose used 3) the dose-response relationship could depend on the environment and gene polymorphism ADBR2.

This is a prospective phase II study on dose-response relationship and description of the dose-response curve design using a "sparse" and a modeling approach MCP-Mod.

The dose-response relationship will be modeled by sparse data. The investigators will test two doses per child in four designs that will be drawn. These doses will be assessed using Rint technique by a person blinded to the actual dose delivered to the child.

Measurements of 90 children will estimate E0, Imax and D50 (pharmacokinetic constants) with an accuracy of 3.5%, 8.9% and 25.7% respectively.

The bronchodilator used in the study is the Salbutamol as Ventolin ® (GSK) suspension for inhalation as an aerosol at a dose of 100μg per puff. Ventolin ® is used as part of the MA (No. 344 387-3)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In older children and adults, bronchodilator (BD) dose-effect relationship is part of the characteristics of asthma disease. There are no data on BD dose-response relationship in wheezy preschool children whose disease pathophysiology is poorly understood, but may, in part, takes on the characteristics of asthma.

We assume that 1) in young children interrupter resistance (Rint) could be used to measure a BD effect 2) the response to BD may vary depending on the dose used 3) the dose-response relationship could depend on the environment and gene polymorphism ADBR2.

This is a prospective phase II study on dose-response relationship and description of the dose-response curve design using a "sparse" and a modeling approach MCP-Mod.

The dose-response relationship will be modeled by sparse data. We will test two doses per child in four designs that will be drawn. These doses will be assessed using Rint technique by a person blinded to the actual dose delivered to the child.

Measurements of 90 children will estimate E0, Imax and D50 (pharmacokinetic constants) with an accuracy of 3.5%, 8.9% and 25.7% respectively.

The bronchodilator used in the study is the Salbutamol as Ventolin ® (GSK) suspension for inhalation as an aerosol at a dose of 100μg per puff. Ventolin ® is used as part of the MA (No. 344 387-3) clinical implications The demonstration, first, of the possibility for Rint to detect a dose-response to BD will lead, secondly, to the determination of the minimum dose required for the detection of a reversibility in young children using Rint. It will end a long-standing debate about whether, when no Rint change is observed after BD administration in a young child, the child has actually no reversibility or the BD dose used was not sufficient to demonstrate one.

Moreover, the demonstration of a BD dose-response relationship in young children will suggest similarity between wheezy young children and older children and adults with asthma bronchial behaviour that may have possible therapeutic implications.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75012
        • Beydon

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 6 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Any patient between 2 years 6 months and 6 years 11 months of age referred for pulmonary function testing with bronchodilator test, due to recurrent wheezing ,at least three times in the past year, to LFT laboratories at Armand Trousseau, Robert Debré, both in Paris and Arnaud de VILLENEUVE, in Montpellier hospitals
  • No use of bronchodilator in the previous 12 hours before the test
  • Parents gave their signed consent for the study

Exclusion Criteria:

Any patient aged 2 years 6 months and 6 years 11 months :

  • with another chronic lung disease (bronchopulmonary dysplasia, chronic bronchitis, viral sequel, pathology of inhalation, thoracic-pulmonary malformation, tracheomalacia), anatomical or functional abnormality of the pharyngolaryngeal tract (tonsils touching or in contact with the uvula, laryngomalacia, subglottic stenosis, vocal cord paralysis, laryngeal obstruction)
  • taking regular treatment including leukotrienes receptor antagonist during the week before the test.
  • treated with oral glucocorticosteroids within 15 days before the test.
  • without social security insurance
  • with opposition of the family
  • known intolerant to Salbutamol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: salbutamol - dose 1
Metered dose inhaler, 100µg+300µg per puff, administered one day
Drug: salbutamol
Metered dose inhaler, 100µg+300µg per puff, administered one day
Other Names:
  • Salbutamol -100µg+300µg
OTHER: Salbutamol - dose2
Metered dose inhaler, 100µg+500µg per puff, administered one day
Drug: Salbutamol - dose2
Metered dose inhaler, 100µg+500µg per puff, administered one day
Other Names:
  • salbutamol -100µg+500µg
OTHER: Salbutamol - dose3
Metered dose inhaler, 200µg+600µg per puff, administered one day
Drug: Salbutamol -dose3
Metered dose inhaler, 200µg+600µg per puff, administered one day
Other Names:
  • salbutamol -200µg+600µg
OTHER: salbutamol - dose4
Metered dose inhaler, 200µg+200µg per puff, administered one day
Drug: salbutamol -dose4
Metered dose inhaler, 200µg+200µg per puff, administered one day
Other Names:
  • salbutamol -200µg+200µg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Estimate of bronchodilator dose-effect
Time Frame: 90 MINUTES
Estimate of bronchodilator dose-effect in young children using the technique of interruption of airflow.
90 MINUTES

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the minimum dose to be used routinely in a bronchodilator test and study the effect of environment on the dose-effect of the BD and the minimum dose to be used when testing the BD.
Time Frame: 90 minutes

Determine the minimum dose of bronchodilator to use during a routine test to bronchodilator in young children to demonstrate bronchial reversibility.

To study the effect of the environment (preventer treatment, atopy, disease control) on the BD dose-response relationship and the minimum BD dose to use to study bronchodilator response.

Study on the genotype of the beta2-adrenergic receptor as a source of variation in the dose-response to bronchodilator.
90 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (ACTUAL)

January 1, 2014

Study Completion (ACTUAL)

January 1, 2014

Study Registration Dates

First Submitted

November 9, 2011

First Submitted That Met QC Criteria

November 10, 2011

First Posted (ESTIMATE)

November 11, 2011

Study Record Updates

Last Update Posted (ACTUAL)

February 6, 2023

Last Update Submitted That Met QC Criteria

February 3, 2023

Last Verified

July 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P100504
  • 2011-002261-38 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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