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

NCT04762472 | Unknown Phase 4 DMC

• 1 other identifier: 2020-398
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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. 1.To test the hypothesis of pulmonary inflammation and oxidative stress-related vascular dysfunction in PM air pollution.
2. 2.To evaluate the impact of Montelukast treatment as compared with placebo on predictive atherosclerosis surrogates (FMD and IMT).
3. 3.Subclinical atherosclerosis: (a) Endothelial function (brachial FMD) and (b) carotid intima media thickness (CIMT).
4. 4.PM2.5 \& PM10 concentrations: real-time measurement by portable devices twice at home and work sites.
5. 5.Blood inflammatory markers-platelet count, hsCRP and Fibrinogen
6. 6.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).

Conditions

Atherosclerosis, Coronary

Keywords

Air Pollution (PM2.5); Atherosclerotic Surrogate; Brachial Flow-mediated Dilation; Carotid Intima-media Thickness; Montelukast Intervention; Atherosclerosis Prevention

Outcome Measures

Primary Outcomes (2)

• Brachial flow-mediated dilation (FMD)

  Changes in endothelial function (brachial FMD) in %

  At baseline and 26 weeks of interventional treatment

• Carotid intima media thickness (CIMT)

  Changes in carotid intima media thickness (CIMT) in mm

  At baseline and 26 weeks of interventional treatment

Secondary Outcomes (3)

• Changes of platelet count in k/uL

  At baseline and 26 weeks of interventional treatment

• Changes of hsCRP in mg/ml

  At baseline and 26 weeks of interventional treatment

• Changes of Fibrinogen in g/l

  At baseline and 26 weeks of interventional treatment

Study Arms (2)

Montelukast

ACTIVE COMPARATOR

Montelukast 10mg daily (tablet) orally x 26 weeks

Drug: Montelukast Oral Tablet

Montelukast-matched placebo

PLACEBO COMPARATOR

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

Drug: Montelukast Placebo Oral Tablet

Interventions

Montelukast Oral Tablet DRUG

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

Also known as: Montelukast (active)

Montelukast

Montelukast Placebo Oral Tablet DRUG

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

Also known as: Montelukast Placebo (control)

Montelukast-matched placebo

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• asymptomatic Chinese adults
• aged 30-60 years with
• concordant ambient PM2.5 exposure, both at home and at workplace.

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese University of Hong Kong: lead
• People's Hospital of Chongqing: collaborator
• Hong Kong University of Science and Technology: collaborator
• Chongqing Medical University: collaborator
• University of Sydney: collaborator

Study Sites (1)

The Chinese University of Hong Kong, Department of Medicine & Therapeutics

Shatin, Hong Kong

Location

Related Publications (19)

• Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC Jr, Whitsel L, Kaufman JD; American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation. 2010 Jun 1;121(21):2331-78. doi: 10.1161/CIR.0b013e3181dbece1. Epub 2010 May 10.

  PMID: 20458016 RESULT

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• Pope CA 3rd, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, Godleski JJ. Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation. 2004 Jan 6;109(1):71-7. doi: 10.1161/01.CIR.0000108927.80044.7F. Epub 2003 Dec 15.

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• Yu ITS, hui Zhang Y, San Tam WW, Yan QH, Xu YJ, Xun XJ, Wu W, Ma WJ, Tian LW, Tse LA, Lao XQ. Effect of ambient air pollution on daily mortality rates in Guangzhou, China. Atmos Environ 2012;46:528-535.

  RESULT

• Hajat A, Allison M, Diez-Roux AV, Jenny NS, Jorgensen NW, Szpiro AA, Vedal S, Kaufman JD. Long-term exposure to air pollution and markers of inflammation, coagulation, and endothelial activation: a repeat-measures analysis in the Multi-Ethnic Study of Atherosclerosis (MESA). Epidemiology. 2015 May;26(3):310-20. doi: 10.1097/EDE.0000000000000267.

  PMID: 25710246 RESULT

• Munzel T, Herzog J, Schmidt FP, Sorensen M. Environmental stressors and cardiovascular disease: the evidence is growing. Eur Heart J. 2017 Aug 1;38(29):2297-2299. doi: 10.1093/eurheartj/ehx306. No abstract available.

  PMID: 28641401 RESULT

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  PMID: 24509062 RESULT

• Kunzli N, Tager IB. Air pollution: from lung to heart. Swiss Med Wkly. 2005 Dec 10;135(47-48):697-702. doi: 10.4414/smw.2005.11025.

  PMID: 16511705 RESULT

• Woo KS, Chook P, Hu YJ, Lao XQ, Lin CQ, Lee P, Kwok C, Wei AN, Guo DS, Yin YH, Lau K, Leung KS, Leung Y, Celermajer DS. The impact of particulate matter air pollution (PM2.5) on atherosclerosis in modernizing China: a report from the CATHAY study. Int J Epidemiol. 2021 May 17;50(2):578-588. doi: 10.1093/ije/dyaa235.

  PMID: 33349857 RESULT

• Woo KS, Robinson JT, Chook P, Adams MR, Yip G, Mai ZJ, Lam CW, Sorensen KE, Deanfield JE, Celermajer DS. Differences in the effect of cigarette smoking on endothelial function in chinese and white adults. Ann Intern Med. 1997 Sep 1;127(5):372-5. doi: 10.7326/0003-4819-127-5-199709010-00006.

  PMID: 9273828 RESULT

• Woo KS, Chook P, Raitakari OT, McQuillan B, Feng JZ, Celermajer DS. Westernization of Chinese adults and increased subclinical atherosclerosis. Arterioscler Thromb Vasc Biol. 1999 Oct;19(10):2487-93. doi: 10.1161/01.atv.19.10.2487.

  PMID: 10521379 RESULT

• Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb. 1991 Sep-Oct;11(5):1245-9. doi: 10.1161/01.atv.11.5.1245.

  PMID: 1911709 RESULT

• Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Desvarieux M, Ebrahim S, Fatar M, Hernandez Hernandez R, Kownator S, Prati P, Rundek T, Taylor A, Bornstein N, Csiba L, Vicaut E, Woo KS, Zannad F; Advisory Board of the 3rd Watching the Risk Symposium 2004, 13th European Stroke Conference. Mannheim intima-media thickness consensus. Cerebrovasc Dis. 2004;18(4):346-9. doi: 10.1159/000081812. Epub 2004 Nov 2.

  PMID: 15523176 RESULT

• Thomas GN, Chook P, Qiao M, Huang XS, Leong HC, Celermajer DS, Woo KS. Deleterious impact of "high normal" glucose levels and other metabolic syndrome components on arterial endothelial function and intima-media thickness in apparently healthy Chinese subjects: the CATHAY study. Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):739-43. doi: 10.1161/01.ATV.0000118015.26978.07. Epub 2004 Jan 22.

  PMID: 14739120 RESULT

• Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, Lam CW, Metreweli C, Celermajer DS. Effects of diet and exercise on obesity-related vascular dysfunction in children. Circulation. 2004 Apr 27;109(16):1981-6. doi: 10.1161/01.CIR.0000126599.47470.BE. Epub 2004 Apr 5.

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• [17] Lin CQ, Li Y, Yuan ZB, Lau AKH, Li, CC, and Fung JCH. Using satellite remote sensing data to estimate the high-resolution distribution of ground-level PM2.5. Remote Sens. Environ 2015;156:117-128.

  RESULT

• [18] Lin CQ, Liu G, Lau AKH, Li Y, Li CC, Fung JCH, and Lao XQ. High-resolution satellite remote sensing of provincial PM2.5 trends in China from 2001 to 2015. Atmos. Environ 2018;180:110-116

  RESULT

• Kunzli N, Jerrett M, Mack WJ, Beckerman B, LaBree L, Gilliland F, Thomas D, Peters J, Hodis HN. Ambient air pollution and atherosclerosis in Los Angeles. Environ Health Perspect. 2005 Feb;113(2):201-6. doi: 10.1289/ehp.7523.

  PMID: 15687058 RESULT

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

montelukast; Exercise

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Kam Sang Woo

  Adjunct Professor

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kam Sang Woo, MD, FACC

CONTACT

852-90230869; kamsangwoo@cuhk.edu.hk

Mikki Wong

CONTACT

852-26474966; meikiwong@cuhk.edu.hk

Study Design

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

Study Record Dates

• First Submitted: February 9, 2021
• First Posted: February 21, 2021
• Study Start: September 1, 2023
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2025
• Last Updated: February 13, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: These materials will be available and shared on reasonable requests to Prof KS Woo from January 2024 till December 2024.
• Access Criteria: These informations will be available and shared on reasonable requests to Prof KS Woo from January 2024 till December 2024. (kamsangwoo@cuhk.edu.hk/ crec@cuhk.edu.hk)

Locations

HK (1)