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

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.

Conditions

• Atherosclerosis, Coronary

Interventions

DRUG

Montelukast Oral Tablet

i) Montelukast 10mg daily (tablet) orally x 26 weeks

DRUG

Montelukast Placebo Oral Tablet

i) Placebo (Montelukast identical) tablet 1 daily orally x 26weeks

Sponsors & Collaborators

• People's Hospital of Chongqing

  collaborator OTHER

• Hong Kong University of Science and Technology

  collaborator OTHER

• Chongqing Medical University

  collaborator OTHER

• University of Sydney

  collaborator OTHER

• Chinese University of Hong Kong

  lead OTHER

Principal Investigators

• Kam Sang Woo · Adjunct Professor

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

30 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-09-30

Primary Completion

2024-12-30

Completion

2025-12-30

Countries

• Hong Kong

Study Locations