Official Title: “Evaluation of Lovastatin in Severe Persistent Asthma”

This study has two purposes:

1. to determine whether lovastatin, a commonly used medication to lower cholesterol in the blood, can produce beneficial changes in airway inflammation and in the airway smooth muscle

2. to examine whether lovastatin will have favorable changes in asthma symptoms of patients with moderate or severe asthma.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2010

Intervention(s) in this Clinical Trial

• Drug: Lovastatin
  • Lovastatin 20 mg extended release (or placebo) by mouth once daily for weeks 1-4. Liver function test will be checked at week 4 follow up visit. If LFTs are not > 3 times the upper limit of normal, then the subject will have the dose of extended release lovastatin increased to 60 mg once a day for weeks 4-12
• Drug: Placebo
  • Placebo by mouth once daily for weeks 1-4.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Placebo
• Active Comparator: Lovastin

Primary Measures

• Changes in airway smooth muscle biology and inflammatory measures
  • Time Frame: 12 Weeks
    Safety Issue?: No

Secondary Measures

• Changes in asthma control, lung function and quality of life from the baseline visit to the end of the follow-up period
  • Time Frame: 13 weeks
    Safety Issue?: No

Inclusion Criteria:

• Age > 18 years to <65 years
• Severe persistent asthma (per 2002 National Asthma Education and Prevention Program guidelines)
• Treatment with daily fluticasone (500 ug BID) and salmeterol (50 ug BID) during the past 4 or more weeks
• Pre-bronchodilator FEV1 <80% predicted
• Post-bronchodilator improvement in FEV1 of at least 12% and 200 mL or a PC20 to methacholine of <8 mg/mL
• Evidence of inadequate asthma control in the past 2 weeks: use of rescue inhaler > 4 days and >8 occasions in the past 2 weeks, daytime asthma symptoms > 4 days in the past 2 weeks, or 1 or more nocturnal awakening in the past 2 weeks
• No evidence of alternate diagnosis (e.g., sarcoidosis, eosinophilic pneumonia) on bronchoscopy performed as part of routine care in the Refractory Obstructive Lung Disorders clinic.
• Completed research bronchoscopy while on current dose of daily fluticasone and salmeterol within 4 weeks of meeting other inclusion criteria. Note: many patients in the ROLD clinic require a bronchoscopy to confirm the diagnosis of asthma and exclude other diagnosis (e.g., sarcoidosis). These patients are asked to participate in a research protocol (separate from this proposal) that allows investigators to collect additional samples (endobronchial biopses, bronchoalveolar lavage fluid, endobronchial brushings) at the end of the clinical portion of the bronchoscopy {IRB protocol # 15361A entitled, "Airway inflammation in refractory obstructive lung disease (ROLD): understanding markers of inflammation and remodeling"}. This protocol was recently submitted to the IRB in March 2007.

Exclusion Criteria:

• Pregnancy or lactation
• Severe metabolic disease
• Other respiratory or inflammatory disorders (sarcoidosis, emphysema)
• Hypokalemia, dehydration
• Uncontrolled seizure disorder ( 2 or more seizures in last year)
• Major surgery, trauma
• Pre-existing liver disease (AST or ALT >10% above the upper limit of normal)
• Elevated CK (>50% above the upper limit of normal)
• History of alcohol abuse
• Current smokers or ex-smokers with > 10 pack-years of smoking
• Partial ileal bypass surgery
• Concurrent treatment with drugs known to be have potential interactions or associated with rhabdomyolysis (Cimetadine, danazole, delavaridine, diltiazem, fenofiibrate, nefazodone, niacin, protease inhibitors, quinipristoline/dalfopristin, ranolazine, rifampin, telbivudine, telithromycin)
• HIV patients taking protease inhibitors
• History of allergy or intolerance to statin
• Use of 1 or more doses of any cholesterol lowering medication in the previous 12 weeks
• Clinical indication for treatment with statins

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Chicago

Overall Clinical Trial Officials and Contacts

Blanca Camoretti-Mercado, Ph.D. Principal Investigator University of Chicago  

Overall Contact: Blanca Camoretti-Mercado, Ph.D. 773-702-5448 bcamoret@medicine.bsd.uchicago.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00689806

Study ID Number: 15427A

ClinicalTrials.gov Identifier: NCT00689806

Health Authority: United States: Institutional Review Board