Evaluation of Lovastatin in Severe Persistent Asthma

The University of Chicago

Status and phase

Withdrawn

Phase 2

Phase 1

Conditions

Severe Persistent Asthma

Treatments

Drug: Placebo

Drug: Lovastatin

Study type

Interventional

Funder types

Other

Identifiers

NCT00689806

15427A

UL1RR024999 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This study has two purposes:

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

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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 biopsies, 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