Statins Against Bushfire Smoke

NCT07462715 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: H404202039822
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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:

• 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.

Conditions

Healthy Adults

Keywords

bushfire smoke; wildfire; air pollution; cardiovascular function; statin; inflamation; cognitive function

Outcome Measures

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).

  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 (13)

• 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.

Other Outcomes (2)

• Nasopharyngeal Microbiome Composition and Diversity as Assessed by 16S rRNA Sequencing of Nasopharyngeal Swabs Before and After Simulated Bushfire Smoke Exposure

  Pre-exposure (baseline) and the day following the 2-hour simulated bushfire smoke exposure session.

• 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 (i.e., clean air and simulated bushfire smoke)"

Study Arms (4)

Stream 1. Short term atorvastatin

EXPERIMENTAL

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.

Drug: Atorvastatin

Stream 1. Short term placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Stream 2. Long term statin treatment

ACTIVE COMPARATOR

Long-term statin (stream 2): Participants in this study will have been taking a statin medication for at least one year.

Drug: Atorvastatin

Stream 2. Statin naïve comparison group

NO INTERVENTION

Long-term statin (stream 2): The comparison group will be statin naïve with comparable age gender and cardiovascular risk groupings.

Interventions

Atorvastatin DRUG

Statin 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.

Also known as: Another class of statin in those who do not tolerate atorvastatin

Stream 1. Short term atorvastatin; Stream 2. Long term statin treatment

Placebo DRUG

Identical placebo tablets to the atorvastatin tablets used in the intervention group

Stream 1. Short term placebo

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Menzies Institute for Medical Research: lead

Study Sites (1)

Menzies Institute for Medical Research

Hobart, Tasmania, 7000, Australia

Location

MeSH Terms

Conditions

Pemphigus and fogo selvagem

Interventions

Atorvastatin

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Fay Johnston, MD, PhD

  Menzies Institute for Medical Research, University of Tasmania

  PRINCIPAL INVESTIGATOR

• Lieke Scheepers, PhD

  Menzies Institute for Medical Research

  STUDY DIRECTOR

• Quan Huynh, MD, PhD

  Menzies Institute for Medical Research

  STUDY DIRECTOR

Central Study Contacts

Study coordinator

CONTACT

+61 8 6226 4875; sabs@utas.edu.au

Fay Johnston, MD PhD

CONTACT

+61 408 266 652; fayj@utas.edu.au

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This study has two streams. Each stream has a treatment arm and a comparison arm as described below. Stream 1 - Short-term statin treatment (2 days) Triple-blind, individually randomised treatment, parallel-group, placebo-controlled trial of statin, efficacy, with cross-over, order-randomised exposure 4 weeks apart. Stream 2 - Long-term statin treatment (at least one year) Double-blind, parallel-group, usual-care -controlled trial of statin efficacy, trial with cross-over, order-randomised exposure 4 weeks apart.

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 10, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years after the publication of results.
• Access Criteria: Requests for access to de-identified IPD will be considered on a case-by-case basis. Researchers wishing to access the data should contact the principal investigator with a brief description of the proposed analysis. Data sharing will be subject to ethical approval and a data sharing agreement.

Locations

AU (1)