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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

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)


Condition or disease Intervention/treatment Phase
Asthma Drug: salbutamol Drug: Salbutamol - dose2 Drug: Salbutamol -dose3 Drug: salbutamol -dose4 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Study on Dose-response to Bronchodilator Then Bronchodilator Dose-finding Using the Flow Interruption Technique in Children Aged 2.5 TO 6 Years
Study Start Date : January 2012
Actual Primary Completion Date : January 2014
Actual Study Completion Date : January 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: Salbutamol -100µg+300µg

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 Name: salbutamol -100µg+500µg

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 Name: salbutamol -200µg+600µg

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 Name: salbutamol -200µg+200µg




Primary Outcome Measures :
  1. Estimate of bronchodilator dose-effect [ Time Frame: 90 MINUTES ]
    Estimate of bronchodilator dose-effect in young children using the technique of interruption of airflow.


Secondary Outcome Measures :
  1. 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.




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Ages Eligible for Study:   2 Years to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01470755


Locations
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France
Beydon
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Beydon Nicole, MD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01470755     History of Changes
Other Study ID Numbers: P100504
2011-002261-38 ( EudraCT Number )
First Posted: November 11, 2011    Key Record Dates
Last Update Posted: May 23, 2014
Last Verified: July 2011
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Pediatrics
Bronchial wheeze
bronchodilator
lung function
airway resistance
Additional relevant MeSH terms:
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Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action