Myocardial Ischaemia After Exposure to Diesel Exhaust

NCT01661582 | Completed

• 1 other identifier: MIDAS
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Exposure to particulate air pollution is associated with increases in cardiovascular mortality and morbidity. The pathophysiological mechanisms underlying this observation are emerging, and exposure to particulate air pollution has been shown to result in increases in blood pressure and arterial tone, impaired vascular function and an increased tendency for blood to clot as well as an increase in atherosclerotic plaque burden. Recent evidence from panel studies and controlled exposure studies have suggested an increase in myocardial ischaemia (a reduction in blood flow to the heart) following exposure. In this study we aim to investigate directly myocardial (heart) blood flow following exposure to diesel exhaust (as a model of urban air pollution) using CT/PET myocardial perfusion imaging in male patients with stable coronary disease and healthy male controls. We hypothesize that following exposure to dilute diesel exhaust:

1. 1.Myocardial blood flow will be reduced
2. 2.Coronary flow reserve will be impaired
3. 3.The magnitude of impairment will be higher in patients with coronary disease as compared to healthy controls

Conditions

Coronary Heart Disease

Keywords

Air Pollution; Myocardial Ischaemia; Coronary Blood Flow; Diesel Exhaust; Troponin; Electrocardiography

Outcome Measures

Primary Outcomes (1)

• Myocardial blood flow and coronary flow reserve measured by CT/PET O-15 imaging

  Myocardial blood flow will be measured at rest and at peak adenosine stress using CT/PET O-15 myocardial perfusion imaging immediately following exposure to diesel exhaust and filtered air

  Immediately following exposure

Secondary Outcomes (3)

• Coronary flow reserve determined using doppler echocardiography

  1 hour following exposure

• Ultra-sensitive cardiac troponin-I

  Before, 2 and 24 hours following exposure

• ST segment deviation on continuous 12-lead electrocardiography

  During and for the 24 hours aftet exposure

Study Arms (2)

Filtered Air Exposure

PLACEBO COMPARATOR

Subjects will be exposed to filtered air for 1 hour during intermittent exercise in a purpose-built exposure facility

Other: CT/PET Myocardial Perfusion Imaging using O-15 water; Other: Coronary blood flow measured by doppler echocardiography

Dilute Diesel Exhaust Exposure

EXPERIMENTAL

Subjects will be exposed to dilute diesel exhaust (\~300 mcg/m3) for 1 hour during intermittent exercise in a purpose-built exposure facility

Other: CT/PET Myocardial Perfusion Imaging using O-15 water; Other: Coronary blood flow measured by doppler echocardiography

Interventions

CT/PET Myocardial Perfusion Imaging using O-15 water OTHER

Dilute Diesel Exhaust Exposure; Filtered Air Exposure

Coronary blood flow measured by doppler echocardiography OTHER

Dilute Diesel Exhaust Exposure; Filtered Air Exposure

Eligibility Criteria

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

You may qualify if:

• Healthy volunteers will be taking no regular medication, have a normal electrocardiogram and exercise stress test
• Patients with a previous history of myocardial infarction or successful coronary revascularization (PTCA or coronary artery bypass grafting) but without symptoms of angina pectoris will be recruited

You may not qualify if:

• Healthy volunteers:
• Regular medication
• Abnormal 12-lead electrocardiogram
• Abnormal exercise stress test
• Patients with coronary disease
• Acute coronary syndrome within past 3 months
• Impaired left ventricular function
• Significant valvular heart disease
• Left ventricular hypertrophy
• Resting conduction defect
• Digoxin use
• Renal impairment (eGFR \<60 mL/min)
• Hepatic impairment
• Asthma

Sponsors & Collaborators

• University of Edinburgh: lead
• National Institute for Public Health and the Environment (RIVM): collaborator
• British Heart Foundation: collaborator

Study Sites (1)

University of Edinburgh / NHS Lothian

Edinburgh, EH16 4SB, United Kingdom

Location

Related Publications (2)

• Mills NL, Tornqvist H, Gonzalez MC, Vink E, Robinson SD, Soderberg S, Boon NA, Donaldson K, Sandstrom T, Blomberg A, Newby DE. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med. 2007 Sep 13;357(11):1075-82. doi: 10.1056/NEJMoa066314.

  PMID: 17855668 BACKGROUND

• Langrish JP, Watts SJ, Hunter AJ, Shah AS, Bosson JA, Unosson J, Barath S, Lundback M, Cassee FR, Donaldson K, Sandstrom T, Blomberg A, Newby DE, Mills NL. Controlled exposures to air pollutants and risk of cardiac arrhythmia. Environ Health Perspect. 2014 Jul;122(7):747-53. doi: 10.1289/ehp.1307337. Epub 2014 Mar 25.

  PMID: 24667535 DERIVED

MeSH Terms

Conditions

Coronary Disease; Coronary Artery Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• David E Newby, PhD FRCP

  University of Edinburgh

  STUDY CHAIR

• Jeremy P Langrish, MB BCh MRCP

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 9, 2012
• Study Start: September 20, 2012
• Primary Completion: February 13, 2015
• Study Completion: February 13, 2015
• Last Updated: May 9, 2024

Record last verified: 2024-05

Locations

GB (1)