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

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ClinicalTrials.gov Identifier: NCT01470755
Recruitment Status : Completed
First Posted : November 11, 2011
Last Update Posted : May 23, 2014
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE November 9, 2011
First Posted Date  ICMJE November 11, 2011
Last Update Posted Date May 23, 2014
Study Start Date  ICMJE January 2012
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 10, 2011)
Estimate of bronchodilator dose-effect [ Time Frame: 90 MINUTES ]
Estimate of bronchodilator dose-effect in young children using the technique of interruption of airflow.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01470755 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2012)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2011)
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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Dose-response to Bronchodilator and Dose-finding in Child 2.5 to 6 Years - Study Golden
Official Title  ICMJE Study on Dose-response to Bronchodilator Then Bronchodilator Dose-finding Using the Flow Interruption Technique in Children Aged 2.5 TO 6 Years
Brief Summary

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)

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: salbutamol
    Metered dose inhaler, 100µg+300µg per puff, administered one day
    Other Name: Salbutamol -100µg+300µg
  • Drug: Salbutamol - dose2
    Metered dose inhaler, 100µg+500µg per puff, administered one day
    Other Name: salbutamol -100µg+500µg
  • Drug: Salbutamol -dose3
    Metered dose inhaler, 200µg+600µg per puff, administered one day
    Other Name: salbutamol -200µg+600µg
  • Drug: salbutamol -dose4
    Metered dose inhaler, 200µg+200µg per puff, administered one day
    Other Name: salbutamol -200µg+200µg
Study Arms  ICMJE
  • salbutamol - dose 1
    Metered dose inhaler, 100µg+300µg per puff, administered one day
    Intervention: Drug: salbutamol
  • Salbutamol - dose2
    Metered dose inhaler, 100µg+500µg per puff, administered one day
    Intervention: Drug: Salbutamol - dose2
  • Salbutamol - dose3
    Metered dose inhaler, 200µg+600µg per puff, administered one day
    Intervention: Drug: Salbutamol -dose3
  • salbutamol - dose4
    Metered dose inhaler, 200µg+200µg per puff, administered one day
    Intervention: Drug: salbutamol -dose4
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 10, 2011)
90
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2014
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 6 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01470755
Other Study ID Numbers  ICMJE P100504
2011-002261-38 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Beydon Nicole, MD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date July 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP