Asthma Clinical Research Network (ACRN) Trial - Macrolides in Asthma (MIA)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Vernon M. Chinchilli, PhD, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT00318708
First received: April 25, 2006
Last updated: December 28, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: clarithromycin
Drug: fluticasone propionate
Drug: placebo clarithromycin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Asthma Clinical Research Network (ACRN) Trial - Macrolides in Asthma (MIA)

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Asthma Symptoms [ Time Frame: Measured during the 16-week treatment period ] [ Designated as safety issue: No ]
  • Asthma Rescue Medication Use [ Time Frame: Measured during the 16-week treatment period ] [ Designated as safety issue: No ]
  • AM and PM Peak Expiratory Flow (PEF) [ Time Frame: Measured during the 16-week treatment period ] [ Designated as safety issue: No ]
  • Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Measured during the 16-week treatment period ] [ Designated as safety issue: No ]
  • Asthma-specific Quality of Life [ Time Frame: Measured during the 16-week treatment period ] [ Designated as safety issue: No ]
  • Methacholine Provocative Concentration (PC20) [ Time Frame: Measured during the 16-week treatment period ] [ Designated as safety issue: No ]
  • Exhaled Nitric Oxide (eNO) [ Time Frame: Measured during the 16-week treatment period ] [ Designated as safety issue: No ]
  • Blood Cell Counts [ Time Frame: Measured during the 16-week treatment period ] [ Designated as safety issue: Yes ]
  • AM Cortisol [ Time Frame: Measured during the 16-week treatment period ] [ Designated as safety issue: Yes ]
  • Adverse Events [ Time Frame: Measured during the 16-week treatment period ] [ Designated as safety issue: Yes ]

Enrollment: 92
Study Start Date: June 2006
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
clarithromycin 500 mg twice daily (Biaxin) + fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)
Drug: clarithromycin
clarithromycin 500 mg twice daily (Biaxin)
Other Name: Biaxin
Drug: fluticasone propionate
fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)
Other Name: Flovent®
Active Comparator: 2
placebo clarithromycin twice daily + fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)
Drug: fluticasone propionate
fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)
Other Name: Flovent®
Drug: placebo clarithromycin
placebo clarithromycin twice daily

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00318708

Locations
United States, California
University of California, San Diego
San Diego, California, United States, 92093
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Colorado
National Jewish Medical and Research Center
Denver, Colorado, United States, 80206
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University, St. Louis
St. Louis, Missouri, United States, 63130
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest University Health Sciences
Winston Salem, North Carolina, United States, 27157
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555
United States, Wisconsin
University of Wisconsin, Madison
Madison, Wisconsin, United States, 53706
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Principal Investigator: William J. Calhoun, MD University of Texas, Galveston
Principal Investigator: Mario Castro, MD Washington University School of Medicine
Principal Investigator: Robert F. Lemanske, MD University of Wisconsin, Madison
Principal Investigator: Richard J. Martin, MD National Jewish Health
Principal Investigator: Elliot Israel, MD Brigham and Women's Hospital
Principal Investigator: Stephen P. Peters, MD, PhD Wake Forest School of Medicine
Principal Investigator: Homer A. Boushey, MD University of California, San Francsico
Principal Investigator: Stephen I. Wasserman, MD University of California, San Diego
Principal Investigator: Emily DiMango, MD Columbia University
Principal Investigator: Monica Kraft, MD Duke University
Study Chair: Reuben M Cherniack, MD National Jewish Health
  More Information

Additional Information:
Publications:
Responsible Party: Vernon M. Chinchilli, PhD, Distinguished Professor and Chair, Department of Public Health Sciences, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00318708     History of Changes
Other Study ID Numbers: 377, U10HL074231, 5U10 HL074231, 7U10 HL074206, 5U10 HL074208, 5U10 HL074073, 5U10 HL074227, 5U10 HL074225, 5U10 HL074204, 5U10 HL074218, 5U10 HL074212
Study First Received: April 25, 2006
Results First Received: April 27, 2012
Last Updated: December 28, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Clarithromycin
Fluticasone
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on August 18, 2014