MethaCholine Bronchoprovocation Study (MeCIS)

• Sponsor: Johns Hopkins Bloomberg School of Public Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00705341
• Collaborator: Washington University School of Medicine (Other), St. Louis University (Other), Long Island Jewish Medical Center (Other), North Shore University Hospital (Other), Baylor College of Medicine (Other), University of Vermont (Other), Nemours Children's Clinic (Other), University of Florida (Other), Indiana University (Other), Ohio State University (Other), NYU Langone Health (Other), University of Missouri-Columbia (Other), Northwestern University (Other), Louisiana State University Health Sciences Center in New Orleans (Other), University of Miami (Other), University of South Florida (Other), University of California, San Diego (Other), National Jewish Health (Other), Duke University (Other)
• Enrollment: 219
• Locations: 13
• Arms: 4
• Duration (Months): 13
• Patients Per Site: 16.8
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: fluticasone	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 219 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: MethaCholine Bronchoprovocation - Influence of High Potency Inhaled corticoSteroids in Asthma (MeCIS) Study
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at San Diego	San Diego	California	United States	92103
2	The Nemours Children's Clinic	Jacksonville	Florida	United States	32207
3	University of Miami/Univestiy of South Florida	Miami	Florida	United States	33136
4	Northwestern University Memorial Hospital	Chicago	Illinois	United States	60611
5	Indiana University	Indianapolis	Indiana	United States	46202
6	Louisianna State University	New Orleans	Louisiana	United States	70112
7	University of Missouri-Kansas City	Kansas City	Missouri	United States	64108
8	Washington University School of Medicine	St. Louis	Missouri	United States	631110
9	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
10	New York Consortium/Columbia University	New York	New York	United States	10016
11	New York Medical College	Valhalla	New York	United States	10595
12	Ohio State University	Columbus	Ohio	United States	43210
13	Vermont Lung Center at the University of Vermont	Burlington	Vermont	United States	05405

Sponsors and Collaborators

• Johns Hopkins Bloomberg School of Public Health
• 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

Investigators

• Principal Investigator: Kaharu Sumino, MD, St. Louis Asthma Clinical Research Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Asthma Clinical Research Centers website

Publications

None provided.

• Responsible Party: Janet Holbrook, Associate Professor, Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT00705341
• Other Study ID Numbers: ALAACRC07
• First Posted: Jun 26, 2008
• Last Update Posted: Feb 12, 2013
• Last Verified: Feb 1, 2013

• Keywords provided by Janet Holbrook, Associate Professor, Johns Hopkins Bloomberg School of Public Health: Normal Controls
• Additional relevant MeSH terms: Asthma; Fluticasone

Study Results

Participant Flow

Arm/Group Title	Asthmatic Controls for Phase 1	Non Asthmatic Controls for Phase 1	Low Dose, Then High Dose Fluticasone for Phase 2	High Dose, Then Low Dose Fluticasone for Phase 2
Arm/Group Description	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.	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.	People with asthma receive fluticasone at 250 mcg per day (28 days), then wash-out period (28 days), then fluticasone at 1000 mcg per day (28 days) in phase 2.	People with asthma receive fluticasone at 1000 mcg per day 28 days), then wash-out period (28 days), fluticasone at 250 mcg per day (28 days) in phase 2.
Period Title: Phase 1:Control Challenge
STARTED	126	93	0	0
COMPLETED	126	93	0	0
NOT COMPLETED	0	0	0	0
Period Title: Phase 1:Control Challenge
STARTED	0	0	30	32
COMPLETED	0	0	23	28
NOT COMPLETED	0	0	7	4

Baseline Characteristics

Arm/Group Title	Nonasthmatic Controls for Phase 1	Asthmatic Controls for Phase 1	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	93	126	219
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	93 100%	126 100%	219 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33 (13)	38 (15)	35 (14)
Sex: Female, Male (Count of Participants)
Female	56 60.2%	84 66.7%	140 63.9%
Male	37 39.8%	42 33.3%	79 36.1%
Region of Enrollment (participants) [Number]
United States	93 100%	126 100%	219 100%

Outcome Measures

1. Primary Outcome

Title	Methacholine Challenge Test Result for Phase 2
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	4 Weeks of High Dose Fluticasone	4 Weeks of Low Dose Fluticasone
Arm/Group Description	4 weeks of Fluticasone (Flovent diskus) 500 mcg twice daily (1000mcg/day)	4 weeks of Fluticasone (Flovent diskus) 250 mcg once daily
Measure Participants	28	23
Geometric Mean (Full Range) [mg/ml]	1.19	2.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	4 Weeks of High Dose Fluticasone, 4 Weeks of Low Dose Fluticasone
	Comments	Log-linear generalized estimating equation (GEE) models were used to assess the dose effect on PC20.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Regression, Linear
	Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Asthmatic Controls for Phase 1	Non Asthmatic Controls for Phase 1
Arm/Group Description	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.	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.
Measure Participants	126	93
Number (95% Confidence Interval) [% predictive value]	96	75

Adverse Events

Adverse Event Reporting Description	Adverse events were not collected in phase 1 of the study
Arm/Group Title	Low Dose for phase1		High Dose for Phase 2
Arm/Group Description	4 weeks of Fluticasone (Flovent diskus) 250 mcg twice daily (500 mcg/day)		4 weeks of Fluticasone (Flovent diskus) 500 mcg twice daily (1000mcg/day)
All Cause Mortality
	Low Dose for phase1		High Dose for Phase 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Low Dose for phase1		High Dose for Phase 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Low Dose for phase1		High Dose for Phase 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/30 (76.7%)		22/32 (68.8%)
Gastrointestinal disorders
Gastrointestinal discomfort and pain	10/30 (33.3%)		9/32 (28.1%)
Nausea and vomiting	8/30 (26.7%)		5/32 (15.6%)
Diarrhea	4/30 (13.3%)		5/32 (15.6%)
General disorders
headache	22/30 (73.3%)		22/32 (68.8%)
Pharyngitis	13/30 (43.3%)		15/32 (46.9%)
Hoarseness/ dysphoria	12/30 (40%)		16/32 (50%)
Infections and infestations
Sinusitis	5/30 (16.7%)		4/32 (12.5%)
Upper respiratory infection	7/30 (23.3%)		6/32 (18.8%)
Viral lower respiratory infection	2/30 (6.7%)		5/32 (15.6%)
Viral gastrointestinal infection	1/30 (3.3%)		1/32 (3.1%)
Influenza	2/30 (6.7%)		4/32 (12.5%)
Fever	6/30 (20%)		6/32 (18.8%)
Injury, poisoning and procedural complications
Injury	5/30 (16.7%)		7/32 (21.9%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	10/30 (33.3%)		10/32 (31.3%)
Muscle injury	3/30 (10%)		6/32 (18.8%)
Respiratory, thoracic and mediastinal disorders
Oral candidiasis	2/30 (6.7%)		3/32 (9.4%)
Nasal congestion	23/30 (76.7%)		22/32 (68.8%)
Rhinitis	18/30 (60%)		19/32 (59.4%)
Cough	19/30 (63.3%)		19/32 (59.4%)
Upper respiratory inflammation	11/30 (36.7%)		9/32 (28.1%)
Bronchitis	3/30 (10%)		4/32 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.