- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00318708
Asthma Clinical Research Network (ACRN) Trial - Macrolides in Asthma (MIA) (MIA)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Asthma prevalence has steadily increased in the United States since the early 1980s; currently, more than 20 million people are diagnosed with asthma. Individuals with this disease may experience periodic attacks of wheezing, shortness of breath, chest tightness, and coughing. While there are many known causes of asthma, including tobacco smoke and other allergens, the exact cause of some asthma cases remains unknown. Research has shown that in some individuals, respiratory airway infections may play a role in the onset and severity of the disease. Inhaled corticosteroids are commonly used to treat asthma; however, they do not effectively control symptoms for everyone. Clarithromycin, an antibiotic medication used to treat bacterial infections, may be an effective asthma treatment for individuals who do not respond well to inhaled corticosteroids. The purpose of this study is to evaluate the effectiveness of clarithromycin at reducing asthma symptoms.
This study will begin with a 4-week run-in period to standardize participants' asthma medication usage. During this time, all participants will stop their current asthma medications and instead will receive inhaled fluticasone twice a day. Albuterol will be available as a rescue medication if necessary. Study visits will take place every 2 weeks. Blood and saliva samples will be obtained for laboratory tests and participants will complete standardized questionnaires to assess asthma symptoms and quality of life. Spirometry will be performed to measure lung function. Medication adherence will be monitored with a daily diary and an electronic pill counting device. At the end of Week 4, participants will be evaluated for study eligibility. If eligible, participants will undergo a bronchoscopy and a lung biopsy to test for Mycoplasma pneumoniae and Chlamydia pneumoniae, two bacteria that have been identified as possible factors in the development of asthma.
The treatment phase of the study will last 16 weeks. Participants will be randomly assigned to receive either 500 mg of clarithromycin or placebo twice a day, plus inhaled fluticasone. At monthly study visits, spirometry and blood collection will be performed. Standardized questionnaires to assess asthma symptoms will be completed every 2 weeks. Medical adherence will continue to be monitored. At the end of Week 16, participants will stop receiving clarithromycin or placebo, but will continue to receive fluticasone. Asthma symptoms, rescue medication usage, quality of life, and lung capacity will be assessed; tissue samples will be examined for the presence of Mycoplasma pneumoniae and Chlamydia pneumoniae. An 8-week washout period will follow to observe any lingering medication effects and to monitor for safety. Monthly study visits during this period will include spirometry and blood collection.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
California
-
San Diego, California, United States, 92093
- University of California, San Diego
-
San Francisco, California, United States, 94143
- University of California, San Francisco
-
-
Colorado
-
Denver, Colorado, United States, 80206
- National Jewish Medical and Research Center
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Brigham & Women's Hospital
-
-
Missouri
-
Saint Louis, Missouri, United States, 63130
- Washington University, St. Louis
-
-
New York
-
New York, New York, United States, 10032
- Columbia University Medical Center
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Duke University Medical Center
-
Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences
-
-
Texas
-
Galveston, Texas, United States, 77555
- University of Texas Medical Branch
-
-
Wisconsin
-
Madison, Wisconsin, United States, 53706
- University of Wisconsin, Madison
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- History of physician-diagnosed asthma
- Methacholine PC20 less than or equal to 16 mg/ml and/or FEV1 improvement greater than or equal to 12% in response to 180 mcg albuterol
- Stable asthma for at least 6 weeks prior to study entry
- FEV1 greater than or equal to 60% of predicted result following 180 mcg albuterol
- Juniper ACQ score greater than or equal to 1.5 (optimal ACQ score cut-off point for asthma that is "not well-controlled" by NIH/Global Initiative for Asthma [GINA] guidelines)
- Nonsmoker (less than 10 pack-per-year lifetime smoking history and no smoking in the year prior to study entry)
- Able to perform spirometry, as per American Thoracic Society criteria
- 75% adherence with diary cards, fluticasone (monitored with Doser), and placebo pill trial (monitored electronically with Electronic Drug Exposure Monitor [eDEM] pill dose counter) for the final 2 weeks of the four-week run-in period
- At Visit 1, in steroid-naïve participants, no significant adrenal suppression, defined as a plasma cortisol concentration less than 5 mcg/dL. If adrenal suppression occurs, a 250 mcg corticotropin (ACTH) stimulation test will be performed. Plasma cortisol levels will be collected at baseline, and 30 and 60 minutes after the ACTH stimulation test. Participants must have a cortisol concentration greater than 20 mcg/dL on at least one of the post-ACTH time points
- Absence of bronchoscopy-induced exacerbation; if bronchoscopy-induced exacerbation has occurred, prednisone therapy must have stopped at least 6 weeks prior to study entry
- Absence of respiratory tract infection; if infection has occurred, infection-related symptoms must have stopped at least 6 weeks prior to study entry
- Has experienced no more than two exacerbations or respiratory tract infections prior to study entry
- If female and able to conceive, willing to utilize two medically acceptable forms of contraception (one non-barrier method with single barrier method OR double barrier method)
Exclusion Criteria:
- Presence of lung disease other than asthma
- Presence of vocal cord dysfunction, due to potential confounding of ACQ score
- Significant medical illness other than asthma
- History of atrial or ventricular tachyarrhythmia
- Use of any medication that has a significant interaction with clarithromycin, including herbal or alternative therapies
- Asthma exacerbation within 6 weeks of the screening visit or during the run-in period prior to bronchoscopy
- Use of systemic steroids or change in dose of controller therapy within 6 weeks of the screening visit
- Inability, in the opinion of the study investigator, to coordinate use of dry powder or metered-dose inhaler or to comply with medication regimens
- Inability or unwillingness to perform required study procedures
- Prolonged heart rate corrected QT-interval (greater than 450 msec in women and greater than 430 msec in men) on echocardiogram (ECG) at study entry
- Low potassium or magnesium levels (based on local Asthma Clinical Research Network laboratory definitions)
- Abnormal elevation of liver function tests (AST, ALT, total bilirubin, or alkaline phosphatase)
- Abnormal prothrombin time (PT) or partial thromboplastin time (PTT) results
- Reduced creatinine clearance
- Contraindication to bronchoscopy, as determined by medical history or physical examination
- Regular consumption of grapefruit or grapefruit juice
- Pregnant or breastfeeding
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: clarithromycin + fluticasone
clarithromycin 500 mg twice daily (Biaxin) + fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)
|
clarithromycin 500 mg twice daily (Biaxin)
Other Names:
fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)
Other Names:
|
Active Comparator: placebo + fluticasone
placebo clarithromycin twice daily + fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)
|
fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)
Other Names:
placebo clarithromycin twice daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Juniper Asthma Control Questionnaire (ACQ) Results
Time Frame: Measured every four weeks during the 16-week treatment period, with the change (week 16 minus baseline) as the primary outcome
|
The Juniper asthma control questionnaire (ACQ) consists of six questions answered by the asthma patient with respect to symptoms, rescue medication use, and night-time awakenings due to asthma.
A seventh item in the ACQ is the percent predicted FEV1.
Each of the seven items is scored from from 0 (best) to 6 (worst), and then the seven items are averaged to yield a number from 0 (best) to 6 (worst).
Asthma patients needed to display an ACQ greater than or equal to 1.25 in order to be eligible for randomization.
A reduction of 0.5 units or more in the ACQ over the 16 weeks of treatment is considered to be clinically significant.
|
Measured every four weeks during the 16-week treatment period, with the change (week 16 minus baseline) as the primary outcome
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Asthma Rescue Medication Use
Time Frame: the week-16 average minus the baseline-week average
|
number of rescue puffs per day
|
the week-16 average minus the baseline-week average
|
AM Peak Expiratory Flow (PEF)
Time Frame: the week-16 average minus the baseline-week average
|
daily AM peak expiratory flow (PEF) measured in liters per minute
|
the week-16 average minus the baseline-week average
|
Forced Expiratory Volume in One Second (FEV1)
Time Frame: the week-16 value minus the baseline-value
|
Forced expiratory volume in one second (FEV1) from spirometry
|
the week-16 value minus the baseline-value
|
Methacholine Provocative Concentration (PC20)
Time Frame: the week-16 value minus the baseline-value
|
Logarithm-base 2 transformed Methacholine provocative concentration (PC20) based on FEV1
|
the week-16 value minus the baseline-value
|
Exhaled Nitric Oxide (eNO)
Time Frame: the week-16 value minus the baseline-value
|
Exhaled nitric oxide (eNO) measured in parts per billion
|
the week-16 value minus the baseline-value
|
Asthma Quality of Life Questionnaire (AQLQ)
Time Frame: the week-16 value minus the baseline-value
|
The Asthma Quality of Life Questionnaire (AQLQ) consists of 32 questions, with each question ranging from 1 (worst) to 7 (best).
The 32 questions are averaged to yield an overall score, which is reported here.
Therefore, a positive change between the 16-week score and the baseline score represents improvement.
|
the week-16 value minus the baseline-value
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: William J. Calhoun, MD, University of Texas, Galveston
- Principal Investigator: Homer A. Boushey, MD, University of California, San Francsico
- Study Chair: Reuben M Cherniack, MD, National Jewish Health
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Dermatologic Agents
- Anti-Bacterial Agents
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Protein Synthesis Inhibitors
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Anti-Allergic Agents
- Fluticasone
- Xhance
- Clarithromycin
Other Study ID Numbers
- 377
- U10HL074231 (U.S. NIH Grant/Contract)
- 5U10HL074231 (U.S. NIH Grant/Contract)
- 7U10HL074206 (U.S. NIH Grant/Contract)
- 5U10HL074208 (U.S. NIH Grant/Contract)
- 5U10HL074073 (U.S. NIH Grant/Contract)
- 5U10HL074227 (U.S. NIH Grant/Contract)
- 5U10HL074225 (U.S. NIH Grant/Contract)
- 5U10HL074204 (U.S. NIH Grant/Contract)
- 5U10HL074218 (U.S. NIH Grant/Contract)
- 5U10HL074212 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Asthma
-
Vanderbilt University Medical CenterNot yet recruitingAsthma in Children | Asthma Attack | Asthma Acute | Acute Asthma Exacerbation | Asthma; StatusUnited States
-
University of California, San FranciscoCompletedAsthma in Children | Asthma Attack | Asthma Acute | Asthma ChronicUnited States
-
SingHealth PolyclinicsNot yet recruitingAsthma | Asthma in Children | Asthma Attack | Asthma Acute | Asthma Chronic
-
Johann Wolfgang Goethe University HospitalCompleted
-
Universita di VeronaCompleted
-
Parc de Salut MarActive, not recruitingAsthma in Children | Persistent Asthma | Asthma ExacerbationSpain
-
Forest LaboratoriesCompleted
-
Brunel UniversityKarolinska InstitutetUnknown
-
Value Outcomes Ltd.AstraZenecaCompletedAsthma, Bronchial | Bronchial Asthma | Asthma Chronic | Asthma; EosinophilicCzechia
Clinical Trials on clarithromycin
-
Grünenthal GmbHCompletedOtitis Media | Bronchitis | Tonsillitis | PharyngitisGermany, Poland
-
CTI BioPharmaCovanceCompletedDrug Interaction StudyUnited States
-
AbbottCompletedAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB).United States, Canada, Puerto Rico
-
HK inno.N CorporationCompletedHealthyKorea, Republic of
-
Memorial Sloan Kettering Cancer CenterCompletedLymphomaUnited States
-
Lynn Marie TrottiCompletedNarcolepsy | Idiopathic Hypersomnia | HypersomniaUnited States
-
University Medical Center GroningenCompletedMultidrug-resistant Tuberculosis | Extensively Drug-resistant TuberculosisNetherlands
-
AbbottEilafCompletedRespiratory Tract InfectionEgypt, Saudi Arabia
-
University of KarachiCenter for Bioequivalence Studies and Clinical Research; Merck Pvt. Ltd, PakistanCompletedHealthy Volunteers | Bioequivalence StudyPakistan
-
Assistance Publique - Hôpitaux de ParisCompletedHelicobacter Pylori InfectionFrance