Randomised Controlled Trial to Evaluate the Effect of Statins on Asthma Control of Patients With Chronic Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Change in PEFR
研究概览
简要总结
Statins are the most common type of cholesterol-lowering drugs used in clinical practice. Recent research suggests that they may also have anti-inflammatory properties, in particular by inhibition of an important inflammatory cell called a T lymphocyte. Asthma is characterised by chronic inflammation in the airways, which is thought to be regulated by the activity of T lymphocytes. The investigators have found the anti-inflammatory activity of a statin drug in an experimental model of allergic asthma and they have recently shown the beneficial effects of a statin, atorvastatin, in patients with rheumatoid arthritis. These findings demonstrate the therapeutic potential of statin-sensitive pathways in allergic airways disease. The investigators plan to perform a "proof of concept" study to determine the effectiveness of statin therapy in asthma. This randomised controlled trial will test the hypothesis that statins improve asthma control of patients with chronic asthma. The study will be a 22-week randomised controlled trial comparing the effect on asthma control of oral atorvastatin with that of a matched placebo. Each treatment will be administered for 8 weeks separated by a 6-week washout period. A total of 52 allergic asthmatic patients will be recruited to ensure that 44 patients complete the study. The investigators will examine the effect of statin therapy on lung function, symptom scores, exacerbation rates, as well as on the measurement of airway inflammation in sputum and in the blood. This study will determine the benefit of atorvastatin as an add-on therapy in asthma and establish if statins might have a role in asthma management.
详细描述
Study Design:
The study will be a 24-week randomised double blind crossover study comparing the effect on asthma control of oral atorvastatin therapy (40 mg daily) with that of a matched placebo. Each treatment will be administered for 8 weeks separated by a 6-week washout period and a 2-week run-in period prior to randomisation. Randomisation will be performed in sequential blocks.
Patients will be assessed on 9 visits (13 occasions, as some visits are performed over 2 days): -
Visit 1: Screening visit:
- Obtain written informed consent
- General medical history & physical examination
- Complete asthma control questionnaire
- Spirometry and reversibility testing.
- Blood sampling (35 ml) for IgE serology, lipids, liver function tests, creatinine kinase and immunological tests (including sVCAM-1, Sicam-1, Spcam, E-selectin, CRP, MCP-1, IL-6, IL-10 and TNF-alpha.).
- Eligibility check
- Issue diary card and peak flow meter
- Adjustment of asthma medication to BTS guidelines if required.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of asthma: This will be established symptomatically by episodic wheezing, chest tightness and/or dyspnoea and objectively confirmed by methacholine airway hyperresponsiveness or by evidence of variable airflow obstruction with an increase in FEV1 of > 12% following nebulised salbutamol (2.5mg) or diurnal peak flow variability of > 20% for 3 days in a week (with a minimum change of 60 L) during the run-in period of the study (BTS).
- •Age range of 18-70 years
- •Duration of asthma > 1 year and on stable medication for 4 weeks
- •Receiving regular inhaled steroid treatment (≤ 1000mcg Beclomethasone equivalent daily) and no other medication for their asthma other than a short-acting bronchodilator.
- •Symptomatic, defined as an asthma control questionnaire score of 1 (range 0-6) prior to randomisation or use of inhaled beta2-agonist on 5 or more days in the week before randomisation or FEV1 reversibility >12% or diurnal peak flow variability of >20% during the run-in period of the study for at least 3 days of a week.
- •Stable asthma medication for at least 4 weeks prior to randomisation
- •Written informed consent
排除标准
- •Inability to demonstrate correct use of peak flow meter after instruction
- •Current smokers or ex-smokers of < 1 year or ex-smokers who have smoked > 5 pack years.
- •Patients with unstable asthma, defined as the presence of 1 or more of the following events in the month prior to randomisation: *emergency/'out of hours' visits of patients to the GP; *GP visit to patient at home; *A & E hospital attendance; *hospital admission.
- •Patients in whom cardiovascular risk requires statin therapy
- •Any known sensitivity or adverse reaction to statin, or previous evidence of myopathy or myositis plus creatinine kinase and liver function tests > x2 upper limit of normal range.
- •Non-atopic asthma (specific IgE skin test negative to common allergens) [skin test wheal </= 3mm over negative control saline]
- •Patients who show specific IgE sensitivity or are skin test positive to grass pollen allergen will not be recruited from mid May to the end of July (grass allergen season in the United Kingdom [UK]).
- •Pregnancy/lactation. Patients who require medications known to interact with statins, such as azole antifungal agents, erythromycin, clarithromycin, cyclosporine, gemfibrozil, verapamil and amiodarone.
- •Inability to fully comprehend the patient information sheet.
研究组 & 干预措施
1
Oral atorvastatin 40mg
干预措施: Atorvastatin (Drug)
2
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in PEFR
时间窗: 8 weeks of treatment
次要结局
- Change in health-related quality of life (HR-QOL)(8 weeks)
- Change in asthma control score (Juniper)(8 weeks)
- Change in inflammatory markers(8 weeks)