None listed
Conditions
Brief summary
In atopic asthma the airways are infiltrated with eosinophils (a type of white blood cell). Usually it is responsive to inhaled steroid (ICS) therapy. However, the response to steroid is very variable. In some cases very high doses of inhaled steroid are needed, with the risk of side effects such as skin thinning and cataracts. There is a question of whether there may be steroid resistance. Thus there is a need for alternative and/or additional non-steroidal anti-inflammatory therapies in bronchial asthma. Statins, which lower cholesterol, have anti-inflammatory effects. This study will investigate simvastatin as an anti-inflammatory treatment in eosinophilic asthma. It will be a randomised, double-blind, cross-over trial of simvastatin versus placebo. Participants will initially undergo steroid withdrawal to determine their type of asthma (eosinophilic or not). Those with eosinophilic asthma will commence high dose ICS, followed by back titration of the dose on both simvastatin and placebo. The aim will be to determine the optimum dose when the patient is receiving the active drug compared to placebo. We will measure inflammatory markers during both arms of the study. The data obtained will confirm whether or not statin therapy has a beneficial anti-inflammatory effect.
Interventions
This study will investigate simvastatin as an anti-inflammatory treatment in eosinophilic asthma. It will be a randomised, double-blind, cross-over trial of simvastatin versus placebo. During phase 1 (lasting up to 28 days) participants will undergo steroid withdrawal to determine their type of asthma (eosinophilic or not). Those wit
This study will investigate simvastatin as an anti-inflammatory treatment in eosinophilic asthma. It will be a randomised, double-blind, cross-over trial of simvastatin versus placebo. During phase 1 (lasting up to 28 days) participants will undergo steroid withdrawal to determine their type of asthma (eosinophilic or not). Those with eosinophilic asthma will then enter phase 2 and commence high dose inhaled corticosteroid (fluticasone 1000mcg daily) to determine steroid responsiveness over 4 weeks. In phase 3 , participants will commence inhaled fluticasone 500mcg daily and in addition will be randomised to receive either oral simvastatin 40mg daily or oral placebo. Thereafter the fluticasone dose will be reduced every 4 weeks until "poor control" as judged by symptoms, peak flow, requirement for reliever therapy/bronchodilator and spirometry - this part of phase 3 will be of variable duration up to a maximum of 20 weeks if the participant gets off steroid altogether. Dose steps will be 500mcg, 250mcg, 100mcg, 50mcg and 0mcg daily. At “poor control”, each patient will be stepped up to the previous fluticasone dose step for a further four weeks (optimum dose). Thereafter, each patient will be continued on optimal dose of fluticasone for a further 4 weeks but with simvastatin/placebo discontinued. They will then proceed back to the beginning of phase 3 and receive the alternative treatment (simvastatin/ placebo). There will not be a washout period between the 2 runs of phase 3 as for the last 4 weeks of the first run of phase 3 simvastatin/placebo will have been discontinued. The aims will be to determine the optimum dose of fluticasone when the patient is receiving the active drug compared to placebo and to identify any possible steroid sparing effects of simvastatin.
Sponsors
Professor D Robin Taylor
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients with chronic persistent asthma, diagnosed according to American Thoracic Society (ATS) criteria. Each patient will be stable at entry with no change in inhaled steroid treatment during the previous 6 weeks.
Exclusion criteria
Smokers or ex-smokers with cumulative consumption of >10 pack years; other co-existing respiratory disease, co-morbidity likely to influence the conduct of the study; pregnancy or women of child-bearing potential who are not using regular contraception; history of adverse reaction or contraindication to statin drugs, inability to do without long-acting beta-agonist inhaler.
Outcome results
None listed