The Long-term Prognosis of Moderate to Severe Bronchial Hyperresponsiveness (BHR) in Asthmatic Preschool Children

This study has suspended participant recruitment.
(2006 data will be analyzed. Due to few capacities 2011 to 2016 will be supended.)
Sponsor:
Information provided by (Responsible Party):
Johannes Schulze MD, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT01144910
First received: June 1, 2010
Last updated: September 19, 2012
Last verified: September 2012
  Purpose

The aim of investigator´s clinical trial is to investigate 52 patients aged three to five years with viral-induced asthma and 52 patients aged three to five years with allergic asthma. Over a time-span of 5 years the investigators will explore lung function and bronchial responsiveness. The investigators plan to evaluate long-term clinical history of moderate to severe bronchial hyperresponsiveness in preschool children with asthma. Therefore factors like atopy in children, parental atopy and bronchial hyperresponsiveness will be explored.


Condition Intervention
Intrinsic Asthma
Allergic Asthma
Allergy
Bronchial Hyperresponsiveness
Other: methacholine challenge test

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective, Open Label, Single-center Study of the Long-term Prognosis of Moderate to Severe Bronchial Hyperresponsiveness (BHR) in Asthmatic Preschool Children.

Resource links provided by NLM:


Further study details as provided by Johann Wolfgang Goethe University Hospitals:

Primary Outcome Measures:
  • Change of severe bronchial hyperresponsiveness over time of five years. [ Time Frame: five years ] [ Designated as safety issue: No ]
    Bronchial hyperresponsiveness will be defined by the provocation dose (PD) of methacholine causing a 20% drop of FEV1 (PD-20FEV1).


Secondary Outcome Measures:
  • Bronchial responsiveness of parents [ Time Frame: two years ] [ Designated as safety issue: No ]
    In parents at first visit bronchial hyperresponsiveness will be defined by the provocation dose (PD) of methacholine causing a 20% drop of FEV1 (PD-20FEV1).

  • Impact of atopy [ Time Frame: five years ] [ Designated as safety issue: No ]
    Influence of atopy on the time course of bronchial hyperresponsiveness.

  • eNO [ Time Frame: five years ] [ Designated as safety issue: No ]
    Influence of the level of exhaled NO on the time course of BHR.

  • Total-IgE [ Time Frame: five years ] [ Designated as safety issue: No ]
    Influence of the level of total-IgE on the time course of BHR


Biospecimen Retention:   Samples With DNA

whole blood, serum, sputum


Estimated Enrollment: 104
Study Start Date: May 2011
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
BHR non-atopy
Patients from the outpatient Department of Allergy, Pneumology and Cystic fibrosis, children's hospital, Goethe-University, Frankfurt, Germany. Over a time-span of 5 years the investigators will explore the lung function and the bronchial hyperresponsiveness. Bronchial methacholine challenges will be performed at baseline and after 1, 3 and 5 years.
Other: methacholine challenge test

2 ml of liquid-dissolved methacholine in concentration of 16 mg/ml dosed in 5 steps of 0.01 mg, 0.1 mg, 0.4 mg, 0.8 mg, and 1.6 mg. 2 minutes after each step up an impulse oscillometry (IOS) and spirometry will be performed.

the challenge will be stopped in case of a ≥ 20% decrease from baseline in FEV1 (PD20) and 0,2 mg Salbutamol will be given.

Other Name: There are no other names
BHR atopy
Patients from the outpatient Department of Allergy, Pneumology and Cystic fibrosis, children's hospital, Goethe-University, Frankfurt, Germany. Over a time-span of 5 years the investigators will explore the lung function and the bronchial hyperresponsiveness. Bronchial methacholine challenges will be performed at baseline and after 1, 3 and 5 years.
Other: methacholine challenge test

2 ml of liquid-dissolved methacholine in concentration of 16 mg/ml dosed in 5 steps of 0.01 mg, 0.1 mg, 0.4 mg, 0.8 mg, and 1.6 mg. 2 minutes after each step up an impulse oscillometry (IOS) and spirometry will be performed.

the challenge will be stopped in case of a ≥ 20% decrease from baseline in FEV1 (PD20) and 0,2 mg Salbutamol will be given.

Other Name: There are no other names.

Detailed Description:

A positive family history with prevalence of atopy, eczema, wheezing are well-known factors predicting asthma. Caudri et al. found more important predictors like perinatal transmission, parental use of inhalative medications and wheezing/dyspnea out of viral infections(5). Measurement of BHR in children was in most studies a second outcome parameter.

Four visits will be performed, baseline and after 1, 3, and 5 years. At visit 1 the investigators will characterize all patients by a ISAAC survey. At each visit in children a methacholine challenge, a skin Prick test, eNO, RAST and total IgE will be performed. At visit 3 and 4 sputum will be induced. In parents only at the first visit a methacholine challenge will be performed. A genetic identification of ADAM33 gene from EDTA blood shall be provided. ADAMs are multidomain proteins with a metalloprotease domain, associated with airway remodelling. Visits should be kept in a time interval without asthma therapy and respiratory infection.

To examine the feasibility of methacholine challenges in preschool children data measured in 2006 will be analysed.

  Eligibility

Ages Eligible for Study:   3 Years to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

patients from the outpatient Department of Allergology, Pneumology and Cystic fibrosis, children's hospital, Goethe-University, Frankfurt, Germany

Criteria

Inclusion Criteria:

  • informed consent
  • age 3 to 6 years
  • diagnosis asthma
  • pulmonary function: FEV1 (% pred.)≥ 70%
  • ability to carry out 2 reproducible flow volume loops
  • moderate to severe BHR (PD20 FEV1 ≤ 0,3 mg methacholine)
  • more than 4 weeks interval since last infection
  • 8 hours washout period of Short Acting Beta Agonist
  • 1 week washout period of Ipratropium Bromide
  • 1 week washout period of Long Acting Beta Agonist
  • 4 weeks washout period of Systemic Corticosteroids
  • 4 weeks washout period of Leukotriene Antagonists

Exclusion Criteria:

  • Age < 3 and > 6 Years
  • Pulmonary function test: FEV1 (% pred.) < 70%
  • Others chronic diseases or infections (e.g., HIV, tuberculosis, malignancy)
  • Incapability to perform spirometry
  • Current participation in another clinical trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01144910

Locations
Germany
Goethe University
Frankfurt am Main, Germany, 60590
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospitals
Investigators
Principal Investigator: Johannes Schulze, Dr. Goethe University, Frankfurt, Germany
  More Information

Publications:

Responsible Party: Johannes Schulze MD, Cosultant, Pediadric Allergy, Pulmonology and Cystic fibrosis, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier: NCT01144910     History of Changes
Other Study ID Numbers: KGU-317/09
Study First Received: June 1, 2010
Last Updated: September 19, 2012
Health Authority: Germany: Ethics Commission

Keywords provided by Johann Wolfgang Goethe University Hospitals:
asthma
preschool child
bronchial hyperresponsiveness
methacholine challenge test
atopy

Additional relevant MeSH terms:
Asthma
Bronchial Hyperreactivity
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases
Methacholine Chloride
Autonomic Agents
Bronchoconstrictor Agents
Cholinergic Agents
Cholinergic Agonists
Miotics
Molecular Mechanisms of Pharmacological Action
Muscarinic Agonists
Neurotransmitter Agents
Parasympathomimetics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014