Statins Against Bushfire Smoke
ConditionHealthy Adults
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-68
SponsorMenzies Institute for Medical Research
About this trial
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:
1. 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? 2. 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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Atorvastatin
DrugStatin treatment is being investigated to see if it will modify subclinical adverse cardiovascular effects of bushfire smoke. Controlled dilute bushfire smoke is delivered on two occasions 4 weeks apart in a specialist facility. It is order randomised and masked.
Placebo
DrugIdentical placebo tablets to the atorvastatin tablets used in the intervention group
Treatment groups
100 Participants
are divided into 4 treatment groupsGroup A: Stream 1. Short term atorvastatinExperimental treatment 1 intervention
Group B: Stream 1. Short term placeboPlacebo comparator 1 intervention
Group C: Stream 2. Long term statin treatmentActive comparator 1 intervention
Group D: Stream 2. Statin naïve comparison groupNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
Change in heart rate variability (HRV) associated with smoke exposure in the groups treated with statins, compared with the groups not treated with statins.
Heart rate variability measured as (1) Standard Deviation of Normal-to-Normal intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD).
Time frame
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.Secondary outcomes
1
Change in blood pressure (BP) associated with smoke exposure in the group treated with statins, compared with the group not treated with statins.
Non invasive, ambulant brachial BP is measured using the ABPM-Pro. The first baseline measure is taken a rest with the third of three measures recorded. Thereafter results from a single measurement are recorded every 15 minutes.
Time frame
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.2
Change in aortic vascular stiffness associated with smoke exposure in the group treated with statins, compared with the group not treated with statins.
Aortic vascular stiffness is asses by measuring pulse wave velocity (PWV). PWV from the carotid to the femoral artery is measured with a Sphygmo-cor device using with a carotid tonometer and a femoral BP cuff.
Time frame
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.3
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
Oxidised low-density lipoprotein (oxLDL) is a biomarker of oxidative stress and inflammation. Blood samples will be collected following each 2-hour exposure session (clean air and simulated bushfire smoke) to measure oxLDL levels. Changes in oxLDL between the clean air and simulated bushfire smoke conditions will be compared between participants currently treated with statins and those not treated with statins, to assess whether statin use modifies the oxidative stress response to bushfire smoke exposure.
Time frame
Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.4
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
High-sensitivity C-reactive protein (hsCRP) is a biomarker of systemic inflammation and oxidative stress. Blood samples will be collected following each 2-hour exposure session (clean air and simulated bushfire smoke) to measure hsCRP levels. Changes in hsCRP between the clean air and simulated bushfire smoke conditions will be compared between participants currently treated with statins and those not treated with statins, to assess whether statin use modifies the inflammatory response to bushfire smoke exposure. The two exposure sessions are separated by a minimum washout period of at least 4 weeks.
Time frame
Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.Other outcomes
1
Nasopharyngeal Microbiome Composition and Diversity as Assessed by 16S rRNA Sequencing of Nasopharyngeal Swabs Before and After Simulated Bushfire Smoke Exposure
Nasopharyngeal swabs will be collected using a COPAN swab placed into eNAT medium and frozen for later sequencing analysis at both exposure visits (clean air and simulated bushfire smoke); however, microbiome analysis will only be performed for the simulated bushfire smoke condition.
Time frame
Pre-exposure (baseline) and the day following the 2-hour simulated bushfire smoke exposure session.2
Previous-Day Dietary Intake as Assessed 24-Hour Dietary Recall (assessed by Food frequency Questionnaire Intake24) During Each Environmental Exposure Visit"
During each 2-hour environmental exposure session (clean air and simulated bushfire smoke), participants will be asked to recall all food and drink consumed in the 24 hours prior to the visit. Dietary data will be collected using Intake24, a validated, self-administered multiple-pass 24-hour dietary recall tool completed on a laptop. The multiple-pass method uses structured prompts to improve accuracy of recall. Intake24 captures food and drink items, portion sizes, and eating occasions, from which nutrient and food group intakes are derived. Dietary data will be used as an exploratory variable to assess whether previous-day dietary intake influences the study outcomes
Time frame
During each 2-hour environmental exposure session (i.e., clean air and simulated bushfire smoke)"Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Menzies Institute for Medical Research
Lead sponsor
University of Tasmania
Sponsor institution
Source ClinicalTrials.gov
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