Trial of Simvastatin for the Treatment of Severe Asthma

Randomized Trial of Simvastatin for the Treatment of Severe Asthma

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.

Study Overview

• Status: Withdrawn
• Conditions: Severe Asthma
• Intervention / Treatment: Drug: Simvastatin; Other: Placebo

Detailed Description

See above.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • CTSC Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. statin-naïve adults >18 years old with the ATS definition of severe asthma,
2. on ICS and LABA,
3. confirmation of allergic asthma (serum IgE >100 kU/L, positive radioallergosorbent test (RAST) panel, and/or peripheral blood absolute eosinophil count of ≥700/mm3),
4. clinically stable for 4 weeks.

Exclusion Criteria:

1. baseline FEV1 <30% predicted,
2. current smokers or ex-smokers with >5 pack-years of smoking history,
3. pregnant women, nursing/lactating mothers, or women of childbearing potential who are actively attempting to become pregnant,
4. nasal or sinus surgery or trauma within 3 months of study participation,
5. ischemic heart disease,
6. liver disease, and
7. the concurrent use of the following medications (amiodarone, verapamil, diltiazem, gemfibrozil, cyclosporine, antifungal azoles (itraconazole, ketoconazole, or voriconazole), and danazol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University of California, Davis

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): August 22, 2017
• Study Completion (Actual): August 22, 2017

Study Registration Dates

• First Submitted: April 29, 2015
• First Submitted That Met QC Criteria: May 4, 2015
• First Posted (Estimate): May 5, 2015

Study Record Updates

• Last Update Posted (Actual): September 26, 2017
• Last Update Submitted That Met QC Criteria: September 22, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: simvastatin; severe asthma; allergic airway inflammation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: 522110; 522110-3 (Other Identifier: UC Davis)