Trial of Simvastatin for the Treatment of Severe Asthma

Study Overview
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Brief Summary
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This purpose of this clinical trial is to determine if a statin drug, Simvastatin, added to inhaled corticosteroids and bronchodilators can reduce systemic and airway inflammation, improve lung function and symptoms, and reduce acute exacerbations in patients with severe asthma who are already on controller inhaler therapy. This proposed investigator-initiated, single-center, early Phase II, cross-over, randomized clinical trial, titled Randomized Trial of Simvastatin for the Treatment of Severe Asthma, will be conducted at the University of California, Davis Medical Center (UCDMC) in Sacramento, CA. This trial will evaluate Simvastatin for treatment of asthma in subjects with severe asthma (as defined by the American Thoracic Society (ATS)), who are already taking inhaler controller therapy. The investigators plan to enroll 24 patients with severe allergic asthma. The investigators hypothesize that treatment with Simvastatin 40 mg (administered once daily) will not only improve indicators of airway and systemic allergic/Th2 inflammation, but will also reduce acute exacerbations and improve lung function. All patients will be on standard controller therapy including appropriate doses of inhaled corticosteroids and long-acting bronchodilators.

Detailed Description
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See above.

Official Title
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Randomized Trial of Simvastatin for the Treatment of Severe Asthma

Conditions
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Severe Asthma

Intervention / Treatment
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* Drug: Simvastatin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: statin-naïve adults >18 years old with the ATS definition of severe asthma, on ICS and LABA, confirmation of allergic asthma (serum IgE >100 kU/L, positive radioallergosorbent test (RAST) panel, and/or peripheral blood absolute eosinophil count of ≥700/mm3), clinically stable for 4 weeks. Exclusion Criteria: baseline FEV1 <30% predicted, current smokers or ex-smokers with >5 pack-years of smoking history, pregnant women, nursing/lactating mothers, or women of childbearing potential who are actively attempting to become pregnant, nasal or sinus surgery or trauma within 3 months of study participation, ischemic heart disease, liver disease, and the concurrent use of the following medications (amiodarone, verapamil, diltiazem, gemfibrozil, cyclosporine, antifungal azoles (itraconazole, ketoconazole, or voriconazole), and danazol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simvastatin<br>Simvastatin 40 mg daily will be given for 12 weeks. | Drug: Simvastatin<br>* Simvastatin is used to lower cholesterol, however, it also possess anti-inflammatory and immunomodulatory properties that may also alleviate allergic airway inflammation in asthma.<br>* Other names: Zocor;|
| Placebo Comparator: Placebo<br>A placebo capsule will be given daily for 12 weeks. | Other: Placebo<br>* A placebo pill will be given to the placebo group. There will be no detectible differences between study drug pill and placebo pill.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Th2 gene expression in nasal epithelial cells. | IL13, eotaxin-1,-2,-3, STAT6) by RT-PCR. | Before and after 12 weeks of drug or placebo intervention. | 
| Exhaled nitric oxide (ENO) | ENO will be measured using our NIOX-Mino portable NO analyzer. | Before and after 12 weeks of drug or placebo intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Exacerbations | Assessed as a rate per month. | Before and after 12 weeks of drug or placebo intervention. | 
| Lung function | FEV1, FVC, and FEV/FVC ratio. | Before and after 12 weeks of drug or placebo intervention. | 
| Asthma symptom control score | Asthma Control Test score (5 question survey). | Before and after 12 weeks of drug or placebo intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe asthma, simvastatin, allergic airway inflammation