Asthma
Conditions
Keywords
Normal Controls
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.
Interventions
DRUGfluticasone
Inhaled corticosteroid approved for treatment of asthma
Sponsors
Washington University School of Medicine
St. Louis University
Long Island Jewish Medical Center
North Shore University Hospital
Baylor College of Medicine
University of Vermont
Nemours Children's Clinic
University of Florida
Indiana University
Ohio State University
NYU Langone Health
University of Missouri-Columbia
Northwestern University
Louisiana State University Health Sciences Center in New Orleans
University of Miami
University of South Florida
University of California, San Diego
National Jewish Health
Duke University
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 69 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Methacholine Challenge Test Result for Phase 2 | weeks 0, 4 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Predictive Value of Methacholine Challenge Test for Phase 1 | one time | Predictive value of methacholine challenge test in phase 1 for asthmatics and nonasthmatic controls |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nonasthmatic Controls for Phase 1 People without asthma perform 1 methacholine challenge test in phase 1 to measure the sensitivity and specificity of methacholine challenge testing. Participants did not receive an intervention in phase 1. | 93 |
| Asthmatic Controls for Phase 1 People with asthma perform 1 methacholine challenge test in phase 1 to measure the sensitivity and specificity of methacholine challenge testing. Participants did not receive an intervention in phase 1. | 126 |
| Total | 219 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Phase 2: Trial | Did not meet post-diluent threshold | 0 | 0 | 1 | 0 |
| Phase 2: Trial | Withdrawal by Subject | 0 | 0 | 6 | 4 |
Baseline characteristics
| Characteristic | Asthmatic Controls for Phase 1 | Nonasthmatic Controls for Phase 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 126 Participants | 93 Participants | 219 Participants |
| Age Continuous | 38 years STANDARD_DEVIATION 15 | 33 years STANDARD_DEVIATION 13 | 35 years STANDARD_DEVIATION 14 |
| Region of Enrollment United States | 126 participants | 93 participants | 219 participants |
| Sex: Female, Male Female | 84 Participants | 56 Participants | 140 Participants |
| Sex: Female, Male Male | 42 Participants | 37 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 30 | 22 / 32 |
| serious Total, serious adverse events | 0 / 30 | 0 / 32 |
Outcome results
Primary
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
Time frame: weeks 0, 4
Population: There was a significant period effect in the percentage change in post diluent baseline (PC20) for high- and low-dose depending upon the order in which the doses were administered. In order to remove the effect of the order, we compared the high- and low-dose MCT results exclusively during the first cross over.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 4 Weeks of High Dose Fluticasone | Methacholine Challenge Test Result for Phase 2 | 1.19 mg/ml |
| 4 Weeks of Low Dose Fluticasone | Methacholine Challenge Test Result for Phase 2 | 2.04 mg/ml |
Comparison: Log-linear generalized estimating equation (GEE) models were used to assess the dose effect on PC20.p-value: 0.65Regression, Linear
Secondary
Predictive Value of Methacholine Challenge Test for Phase 1
Predictive value of methacholine challenge test in phase 1 for asthmatics and nonasthmatic controls
Time frame: one time
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 4 Weeks of High Dose Fluticasone | Predictive Value of Methacholine Challenge Test for Phase 1 | 96 % predictive value |
| 4 Weeks of Low Dose Fluticasone | Predictive Value of Methacholine Challenge Test for Phase 1 | 75 % predictive value |