Asthma Clinical Research Network (ACRN) Trial - Macrolides in Asthma (MIA)
Information source: Milton S. Hershey Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Asthma
Intervention: clarithromycin (Drug); fluticasone propionate (Drug); placebo clarithromycin (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Milton S. Hershey Medical Center Official(s) and/or principal investigator(s): William J. Calhoun, MD, Principal Investigator, Affiliation: University of Texas, Galveston Mario Castro, MD, Principal Investigator, Affiliation: Washington University School of Medicine Robert F. Lemanske, MD, Principal Investigator, Affiliation: University of Wisconsin, Madison Richard J. Martin, MD, Principal Investigator, Affiliation: National Jewish Health Elliot Israel, MD, Principal Investigator, Affiliation: Brigham and Women's Hospital Stephen P. Peters, MD, PhD, Principal Investigator, Affiliation: Wake Forest School of Medicine Homer A. Boushey, MD, Principal Investigator, Affiliation: University of California, San Francsico Stephen I. Wasserman, MD, Principal Investigator, Affiliation: University of California, San Diego Emily DiMango, MD, Principal Investigator, Affiliation: Columbia University Monica Kraft, MD, Principal Investigator, Affiliation: Duke University Reuben M Cherniack, MD, Study Chair, Affiliation: National Jewish Health
Summary
Asthma can be caused by a variety of factors, including tobacco smoke, allergens, and
respiratory airway infections. Many people use inhaled corticosteroid medications to treat
their symptoms. These medications, however, are not effective for everyone. Clarithromycin
is an antibiotic that may effectively treat asthma in these individuals. This study will
evaluate the effectiveness of clarithromycin at controlling asthma symptoms.
Clinical Details
Official title: Asthma Clinical Research Network (ACRN) Trial - Macrolides in Asthma (MIA)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Juniper Asthma Control Questionnaire (ACQ) Results
Secondary outcome: Asthma SymptomsAsthma Rescue Medication Use AM and PM Peak Expiratory Flow (PEF) Forced Expiratory Volume in One Second (FEV1) Asthma-specific Quality of Life Methacholine Provocative Concentration (PC20) Exhaled Nitric Oxide (eNO) Blood Cell Counts AM Cortisol Adverse Events
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
University of California, San Diego, San Diego, California 92093, United States
University of California, San Francisco, San Francisco, California 94143, United States
National Jewish Medical and Research Center, Denver, Colorado 80206, United States
Brigham & Women's Hospital, Boston, Massachusetts 02115, United States
Washington University, St. Louis, St. Louis, Missouri 63130, United States
Columbia University Medical Center, New York, New York 10032, United States
Duke University Medical Center, Durham, North Carolina 27710, United States
Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, United States
University of Texas Medical Branch, Galveston, Texas 77555, United States
University of Wisconsin, Madison, Madison, Wisconsin 53706, United States
Additional Information
Click here for the Asthma Clinical Research Network (ACRN) web site
Starting date: June 2006
Last updated: December 28, 2012
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