Air Pollution (PM2.5) on Accelerated Atherosclerosis: A Montelukast Interventional Study in Modernizing China

• Status: Not yet recruiting
• Trial end date: 2023-12-30
• Target enrollment: 0
• Participant gender: All

Summary

Background: Longterm exposure to air pollution has been associated with cardiovascular events and mortality on top of traditional risk factors. Pulmonary inflammation and oxidative stress have been implicated. Brachial (arm) vascular reactivity (flow-mediated dilation FMD) and carotid (neck) artery intima-media thickness (CIMT) are highly reproducible atherosclerosis surrogates, predictive of cardiovascular and stroke outcome. Montelukast is proven safe and effective in alleviating pulmonary inflammation and oxidative stress when used in prevention of asthma episode.

Study objectives:

1. To test the hypothesis of pulmonary inflammation and oxidative stress-related vascular dysfunction in PM air pollution.

2. To evaluate the impact of Montelukast treatment as compared with placebo on predictive atherosclerosis surrogates (FMD and IMT).

Design: Parallel placebo control, randomized comparative study. Subjects will be randomized to take Montelukast (10mg/daily) or image-matched placebo for 26 weeks. Measures will include PM2.5/PM10, indices of subclinical atherosclerosis (brachial FMD and CIMT), blood inflammatory biomarkers (platelet counts, hsCRP and fibrinogen) and potential confounders (lipids and glucose).

Setting: 120 working adults aged 30-60 years in Hong Kong and 80 working adults in Chongqing (CREC Ref No: 2018.157, 2020.398)

Main outcome measures:

1. Subclinical atherosclerosis: (a) Endothelial function (brachial FMD) and (b) carotid intima media thickness (CIMT).

2. PM2.5 & PM10 concentrations: real-time measurement by portable devices twice at home and work sites.

3. Blood inflammatory markers-platelet count, hsCRP and Fibrinogen

4. Potential confounders: we shall collect informations on a range of potential confounders, including other air pollutants and traditional risk factors of atherosclerosis, entrusted to be controlled (stable).

Expected results: Adults after Montelukast treatment and exposed to high levels of PM2.5 or PM10 would have improved (increased) brachial FMD, and reduction of CIMT as compared with placebo. These will have great implication for comparative vascular epidemiology and development of preventive strategies.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Chinese University of Hong Kong
• Collaborators: Chongqing Medical University; Hong Kong University of Science and Technology; People's Hospital of Chongqing; University of Sydney
• Treatments: Montelukast

Criteria

Inclusion Criteria:

• asymptomatic Chinese adults

• aged 30-60 years with

• concordant ambient PM2.5 exposure, both at home and at workplace.

Exclusion Criteria:

• Those with family history of stroke, cardio-vascular disease

• Hypertension with blood pressure >150/90 mmHg

• Diabetics Mellitus

• Overweight/ obesity (BMI >25kg/M2)

• Cigarette smoking or ex-smoker <5 years

• Known dyslipidemia defined as fasting LDL-C >4.1mmol/l and triglyceride >3.0 mmol/l.

• Physical inactivity, with weekly leisure exercise less than 0.5 hour

• Continuous usage of vitamins or herbal medicines in recent one year