Clinical trial NCT00705341: MethaCholine Bronchoprovocation Study (MeCIS)
Official title: MethaCholine Bronchoprovocation - Influence of High Potency Inhaled corticoSteroids in Asthma (MeCIS) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: Normal Controls
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: Washington University School of Medicine
name: St. Louis University
name: Long Island Jewish Medical Center
name: North Shore University Hospital
name: Baylor College of Medicine
name: University of Vermont
name: Nemours Children's Clinic
name: University of Florida
name: Indiana University
name: Ohio State University
name: NYU Langone Health
name: University of Missouri-Columbia
name: Northwestern University
name: Louisiana State University Health Sciences Center in New Orleans
name: University of Miami
name: University of South Florida
name: University of California, San Diego
name: National Jewish Health
name: Duke University
First posted: 2008-06-26
Enrollment: 219
Sex: ALL
Minimum age (years): 12
Maximum age (years): 69
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this research is to evaluate the methacholine challenge test as an accurate indicator of asthma in patients receiving treatment for asthma. Phase 1 on the study compares methacholine challenge test results from asthma patients to those from people who do not have asthma. In phase 2, test results for people with asthma on low dose inhaled corticosteroid will be compared to results on high dose inhaled corticosteroids. Both males and females with stable asthma (asthma participants) and without asthma (controls) enrolled. Participants will be between 12 and 69 years of age.

Detailed description: The study consists of two phases. The first phase is a cross-sectional, case-control study measuring the sensitivity and specificity of methacholine challenge testing for differentiating asthmatic participants from non-asthmatic controls. The second phase is a cross-over, randomized, double-masked trial designed to evaluate the impact of high dose versus low dose inhaled corticosteroids (ICS) on bronchial hyperreactivity (BHR) in asthmatics.

Eligibility criteria: Asthmatic participants

Inclusion Criteria:

* Males or females greater than or equal to 12 and less than 70 years of age
* Physician-diagnosed and investigator-confirmed stable asthma (excluding exercise induced asthma)
* Current treatment for asthma by a healthcare provider within the preceding twelve months: current asthma treatment defined as regular use of asthma medications. Asthma medications include short and long acting adrenergic bronchodilators, bronchodilator combinations, inhaled anticholinergics, inhaled corticosteroids, cromolyn sodium and nedocromil, leukotriene modifiers and methylxanthines
* Stable asthma defined by no asthma exacerbation (emergency room visit, hospitalization, course of increased systemic steroids, or urgent health care visit for asthma) during the prior four weeks
* Forced expiratory volume at one second (FEV1) \>70% predicted pre-bronchodilator
* Ability to provide screening and baseline information
* Ability and willingness to provide informed consent
* For women of childbearing potential: not pregnant, non-lactating, and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study

Exclusion Criteria:

* Chronic oral steroid therapy (daily)
* Oral corticosteroid use within past 4 weeks
* Respiratory tract infection within past 4 weeks
* Chronic diseases (other than asthma) that in the opinion of the investigator would prevent participation in the trial or put the participant at risk by participation, e.g. chronic diseases of the lung (other than asthma), heart, liver, kidney, or nervous system, or immunodeficiency
* Known allergy to methacholine (for example, a previous bad reaction to methacholine) or to any other parasympathomimetic agents
* Current use of beta adrenergic blocking agent (a heart medicine) or a cholinesterase inhibitor (medicine used to treat myasthenia gravis or Alzheimer's disease).
* History of epilepsy, cardiovascular disease with bradycardia (slow heart beat), vagotonia (increased activity of the vagus nerve causing slow heart rate or low blood pressure), peptic ulcer disease, thyroid disease, or urinary tract obstruction
* History of cigarette smoking within the past 5 years or \>10 pack years total
* Use of investigative drugs or intervention trials in the 30 days prior to enrollment or during the duration of the study
* Any condition or compliance issue which in the opinion of the investigator might interfere with participation

Nonasthmatic control criteria:

Inclusion Criteria:

* Males or females greater than or equal to 12 and less than 70 years of age
* Individuals who are in good overall health
* Age (within ten years for above 25 years of age and +/- five years for 12-25 years of age) and sex matched to the asthmatic group

Exclusion Criteria:

* A subject will be excluded if there is a history within the previous 5 years of:

  * clinically diagnosed allergy (allergic rhinitis, hay fever or atopic dermatitis),
  * asthma (beyond 6 years of age),
  * chronic nasal or sinus disease, or
  * other chronic lung diseases
* Respiratory tract infection within past 4 weeks
* History of cigarette smoking within the past 5 years or \>10 pack years total
* Known allergy to methacholine (for example, a previous bad reaction to methacholine) or to any other parasympathomimetic agents
* Current use of beta adrenergic blocking agent (a heart medicine) or a cholinesterase inhibitor (medicine used to treat myasthenia gravis or Alzheimer's disease).
* History of epilepsy, cardiovascular disease with bradycardia (slow heart beat), vagotonia (increased activity of the vagus nerve causing slow heart rate or low blood pressure), peptic ulcer disease, thyroid disease, or urinary tract obstruction

Primary outcomes:
measure: Methacholine Challenge Test Result for Phase 2
timeFrame: weeks 0, 4
Secondary outcomes:
measure: Predictive Value of Methacholine Challenge Test for Phase 1
timeFrame: one time
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: Jacksonville
country: United States
facility: The Nemours Children's Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami/Univestiy of South Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern University Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New Orleans
country: United States
facility: Louisianna State University
state: Louisiana
city: Kansas City
country: United States
facility: University of Missouri-Kansas City
state: Missouri
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: New York Consortium/Columbia University
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Burlington
country: United States
facility: Vermont Lung Center at the University of Vermont
state: Vermont
Study officials:
affiliation: St. Louis Asthma Clinical Research Center
name: Kaharu Sumino, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sumino K, Sugar EA, Irvin CG, Kaminsky DA, Shade D, Wei CY, Holbrook JT, Wise RA, Castro M; American Lung Association Asthma Clinical Research Centers. Methacholine challenge test: diagnostic characteristics in asthmatic patients receiving controller medications. J Allergy Clin Immunol. 2012 Jul;130(1):69-75.e6. doi: 10.1016/j.jaci.2012.02.025. Epub 2012 Apr 1.