MethaCholine Bronchoprovocation Study (MeCIS) (MeCIS)

MethaCholine Bronchoprovocation - Influence of High Potency Inhaled corticoSteroids in Asthma (MeCIS) Study

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: fluticasone

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.

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • University of California at San Diego
  • Florida
    • Jacksonville, Florida, United States, 32207
      • The Nemours Children's Clinic
    • Miami, Florida, United States, 33136
      • University of Miami/Univestiy of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Memorial Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisianna State University
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • University of Missouri-Kansas City
    • St. Louis, Missouri, United States, 631110
      • Washington University School of Medicine
  • New York
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New York, New York, United States, 10016
      • New York Consortium/Columbia University
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Vermont
    • Burlington, Vermont, United States, 05405
      • Vermont Lung Center at The University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 69 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Low dose fluticasone for phase 2; For people with asthma, fluticasone at 250 mcg per day; phase 2 of study	Drug: fluticasone; Inhaled corticosteroid approved for treatment of asthma; Other Names: Flovent diskus
ACTIVE_COMPARATOR: High dose fluticasone for phase 2; For people with asthma, fluticasone at 1000 mcg per day; phase 2 of study	Drug: fluticasone; Inhaled corticosteroid approved for treatment of asthma; Other Names: Flovent diskus
NO_INTERVENTION: Nonasthmatic controls for phase 1; People without asthma will be enrolled to perform 1 methacholine challenge test in phase 1 of the study
NO_INTERVENTION: Asthmatic controls for phase 1; People with asthma will be enrolled to perform 1 methacholine challenge test in phase 1 of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Methacholine Challenge Test Result for Phase 2	Presence and degree of airway hyperresponsiveness assessed by methacholine challenge test post-diluent baseline (PC20) after medication holds; PC20 is the methacholine dose at which the amount of air expired in the first second during a forced expiratory maneuver is reduced by 20%; value represents change in baseline to 4 weeks	weeks 0, 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive Value of Methacholine Challenge Test for Phase 1	Predictive value of methacholine challenge test in phase 1 for asthmatics and nonasthmatic controls	one time

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: University of Missouri-Columbia; Baylor College of Medicine; Washington University School of Medicine; University of California, San Diego; University of South Florida; University of Miami; Northwestern University; NYU Langone Health; Duke University; University of Florida; Ohio State University; University of Vermont; Indiana University; Louisiana State University Health Sciences Center in New Orleans; Nemours Children's Clinic; North Shore University Hospital; Long Island Jewish Medical Center; National Jewish Health; St. Louis University
• Investigators: Principal Investigator: Kaharu Sumino, MD, St. Louis Asthma Clinical Research Center

Publications and helpful links

General Publications

• 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. Erratum In: J Allergy Clin Immunol. 2012 Nov;130(5):1084.

Helpful Links

• Asthma Clinical Research Centers website

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): February 1, 2010
• Study Completion (ACTUAL): February 1, 2010

Study Registration Dates

• First Submitted: June 24, 2008
• First Submitted That Met QC Criteria: June 25, 2008
• First Posted (ESTIMATE): June 26, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): February 12, 2013
• Last Update Submitted That Met QC Criteria: February 11, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Normal Controls
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone
• Other Study ID Numbers: ALAACRC07