Does Short-term or Long-term Statin Use Protect the Heart and Brain During Exposure to Bushfire Smoke? A Parallel-group Statin Trial With Cross-over, Order-randomised Smoke Exposure vs Filtered Air Among Healthy Australian Adults.
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Change in heart rate variability (HRV) associated with smoke exposure in the groups treated with statins, compared with the groups not treated with statins.
研究概览
简要总结
The goal of this clinical trial is to test whether statins can protect the heart and brain from the biological stress and inflammatory responses caused by breathing bushfire smoke in healthy adult volunteers aged 18-64 years. The main questions it aims to answer are:
- Does short-term statin use (2 days) reduce bushfire smoke-induced changes in heart rate variability, blood pressure, arterial stiffness, inflammation and oxidative stress markers, and cognitive function?
- Does long-term statin use (≥12 months) reduce bushfire smoke-induced changes in heart rate variability, blood pressure, arterial stiffness, inflammation and oxidative stress markers, and cognitive function?
The study includes two streams:
Stream 1:short-term statin use (2 days) where participants receive either statin tablets (80mg atorvastatin) or placebo; Stream 2: long-term statin use (≥12 months) where participants include those already taking statins (≥12 months) with statin-naïve individuals.
Participants will:
- Attend two 3½-hour visits to a Climate Hut, which are approximately 4 weeks apart, where they will spend 2 hours exposed to either filtered air or simulated dilute bushfire smoke (average particulate matter (PM2.5) concentration of 300μg/m^3) in randomised order;
- Have continuous heart monitoring with ECG leads and blood pressure checks every 15 minutes during each visit
- Provide urine, saliva, and nose swab samples before and after each exposure, plus follow-up samples the next morning
- Complete cognitive tests (reaction time, memory tasks) and postural balance measurements during exposure
- Complete questionnaires about anxiety levels, symptoms, diet, and health status
- Have blood samples collected and pulse wave velocity measurements (assessing arterial stiffness) immediately after each exposure session.
Potential risks include time commitment, muscle pain from statins, eye irritation or throat discomfort from smoke exposure, and minor discomfort from blood collection.
详细描述
Background and Rationale:
Climate-driven increases in landscape fire activity are substantially increasing population exposure to air pollution, the most important environmental driver of cardiovascular disease (CVD). The 2019-20 Australian bushfires exposed approximately 80% of the population to increased air pollution for several months, resulting in an estimated 429 excess deaths, 3,230 extra hospitalizations for cardiorespiratory problems, and 1,323 emergency presentations for asthma. Despite strong evidence linking air pollution to adverse cardiovascular outcomes, no intervention has been proven effective against bushfire smoke exposure in individuals. Oxidative stress, inflammation, and autonomic dysregulation are key mechanisms underlying these effects. Statins, beyond their cholesterol-lowering properties, have autonomic stabilizing, anti-inflammatory and antioxidant activity that may protect against cardiovascular impacts of air pollution. However, no clinical trials have tested this hypothesis.
Exposure Methodology:
The study utilizes the Climate Hut, a purpose-built facility at the University of Tasmania that allows controlled manipulation of air quality, temperature and humidity. The facility contains a small internal room with one transparent wall enabling observation and communication. Bushfire smoke is generated from eucalyptus fuel burned in a controlled combustion chamber, then diluted and delivered to maintain an average PM2.5 concentration of 300 μg/m³ during 2-hour exposure sessions. This concentration simulates community exposure during planned burns or bushfires and is comparable to smoke experienced at outdoor events with open fire heating. Filtered air sessions use HEPA filtration to remove particulate matter. Real-time monitoring of PM2.5, temperature, and humidity ensures consistent exposure conditions. Each participant undergoes both exposure conditions in randomized order, separated by ≥3 weeks washout period.
Intervention Protocol:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 68 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Good general health and, if aged 45 year or more, low to intermediate (<10%) atherosclerotic cardiovascular disease (ASCVD) risk category, based on clinical data measured within 12 months prior to enrolment.
排除标准
- •History of severe chronic lung diseases such as chronic obstructive pulmonary disease or asthma as determined by participants' care providers.
- •History of chest pain, irregular heartbeats, heart failure, heart attack, heart pacemaker or coronary bypass surgery.
- •High cardiovascular risk (>10%) category on the ASCVD risk calculator or judged to be at high risk by study cardiologist, for those aged 45 years or older.
- •History of stroke, dementia or other neurological condition
- •Untreated high blood pressure (≥ 140 systolic, ≥ 90 diastolic)
- •History of autoimmune or inflammatory rheumatic disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis). Osteoarthritis alone is not an exclusion.
- •History of immunodeficiency
- •Diabetes (any type)
- •Current medications: Long term medications that interact with atorvastatin (such as verapamil, digoxin and warfarin); Medications that affect heart rate variability including beta-blockers (such as atenolol, metoprolol, propranolol, and acebutolol), tricyclic antidepressants and selective serotonin reuptake inhibitors (such as amitriptyline, sertraline, fluoxetine or citalopram), or medications with anti-cholinergic action (such as promethazine or prochlorperazine); stimulant medications, such as those prescribed for ADHD (such as methylphenidate, dexamphetamine, lisdexamfetamine); anti-inflammatory, immunosuppressive or immune modulating medications including systemic corticosteroids (such as prednisolone, dexamethasone) and non-steroidal anti-inflammatory drugs (NSAIDS) (such as ibuprofen, naproxen or diclofenac)
- •Currently smoking, or have smoked: more than one pack of cigarettes in the past year, or have smoked more than 100 packs of cigarettes in their lifetime
- •Currently vaping or have vaped: more than 200 puffs in the last year, more than 20,000 puffs in their lifetime
- •Currently pregnant, attempting to become pregnant or breastfeeding
- •History of skin allergy to tape or electrodes
- •Inability to travel to the study site
研究组 & 干预措施
Stream 1. Short term atorvastatin
Participants randomly assigned to receive statin (80mg atorvastatin) to be taken in the morning the day before and on the morning of the exposure, 1 to 2 hours before each visit.
干预措施: Atorvastatin (Drug)
Stream 1. Short term placebo
Participants randomly assigned to receive placebo tablets identical to the experimental arm, to be taken in the morning the day before and on the morning of the exposure, 1 to 2 hours before each visit.
干预措施: Placebo (Drug)
Stream 2. Long term statin treatment
Long-term statin (stream 2): Participants in this study will have been taking a statin medication for at least one year.
干预措施: Atorvastatin (Drug)
Stream 2. Statin naïve comparison group
Long-term statin (stream 2): The comparison group will be statin naïve with comparable age gender and cardiovascular risk groupings.
结局指标
主要结局
Change in heart rate variability (HRV) associated with smoke exposure in the groups treated with statins, compared with the groups not treated with statins.
时间窗: HRV is measured on two occasions at least 4 weeks apart, one with 2 hours of smoke exposure and one with 2 hours of filtered air exposure. The measurement is continuous over three hours including the half hour before and after the environmental exposure.
Heart rate variability measured as (1) Standard Deviation of Normal-to-Normal intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD).
次要结局
- Change in blood pressure (BP) associated with smoke exposure in the group treated with statins, compared with the group not treated with statins.(BP is measured 15 minutely for 3 hours on two occasions at least 4 weeks apart. Once incorporating 2 hours of smoke exposure and once incorporating 2 hours of filtered air exposure.)
- Change in aortic vascular stiffness associated with smoke exposure in the group treated with statins, compared with the group not treated with statins.(PWV is measured on two occasions at least 4 weeks apart, one immediately following 2 hours of smoke exposure and the other following 2 hours of filtered air exposure.)
- Difference in Oxidised Low-Density Lipoprotein (oxLDL) Levels Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins(Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.)
- Difference in High-Sensitivity C-Reactive Protein (hsCRP) Levels Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins(Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.)
- Difference in Soluble Intercellular and Vascular Cell Adhesion Molecule Levels (sICAM-1 and sVCAM-1) Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins(Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.)
- Difference in Serum Amyloid A (SAA) Levels Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins.(Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks)
- Spatial Working Memory Score as Assessed by the CANTAB Spatial Working Memory Test During Clean Air vs. Simulated Bushfire Smoke Exposure(During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke))
- Cognitive Inhibition and Processing Speed Score as Assessed by the Modified Stroop Test During Clean Air vs. Simulated Bushfire Smoke Exposure(During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke))
- Self-Reported Anxiety Score as Assessed by the State-Trait Anxiety Inventory (STAI) During Clean Air vs. Simulated Bushfire Smoke Exposure(During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke))
- Postural Stability as Assessed by a Standing Balance Test (Floor and Foam Surfaces, Eyes Open and Closed) During Clean Air vs. Simulated Bushfire Smoke Exposure(During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke))
- Symptoms(Collected immediately before and after environmental exposure sessions)
- Salivary cortisol(Collected before and after each environmental exposure session)
- Urinary markers of oxidative stress(A total of three samples will be collected. Before and after each environmental exposure session and the first void urine the following morning.)
研究者
Fay Johnston
Professor
University of Tasmania