Endothelial DysfunctionNCT00775099
Combustion Derived Air Pollution and Vascular Function
A study testing Forearm Vascular Study and Badimon Chamber in people with Endothelial Dysfunction, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
Air pollution is a major cause of cardiovascular morbidity and mortality. The components of air pollution responsible and the mechanisms through which they might mediate these harmful effects remain only partially understood. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Endothelial Dysfunction
- What is being tested?
- Forearm Vascular Study and Badimon Chamber
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2005to Mar 2006
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Healthy volunteers
Who cannot join
- Current smokers
- Significant occupational exposure to air pollution
- History of lung disease
- Women of child-bearing potential
- Malignant arrhythmias
- Renal or hepatic failure
Show all 12Show fewer
- Significant co-morbidity
- Systolic blood pressure >190 or <100 mmHg
- Previous history of blood dyscrasia
- Unable to tolerate the supine position
- Lack of informed consent
- Blood donation within last 3 months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of Combustion-Derived Air Pollution on Vascular Vasomotor and Fibrinolytic Function in Healthy Volunteers (Diesel Exposure)
Air pollution is a major cause of cardiovascular morbidity and mortality. The components of air pollution responsible and the mechanisms through which they might mediate these harmful effects remain only partially understood. The link between cardiovascular disease and air pollution is strongest for fine particulate matter. Fine particulate matter (PM) is produced from the combustion of fossil fuels with the most significant threat thought to be posed by small particles less than 10µm (PM 10) which can be inhaled into the lungs. We propose to identify the precise component of diesel exhaust that mediates the adverse cardiovascular effects using a carbon particle generator, and a particle concentrator. The aim of this study proposal is to assess the vascular effects of different types and components of air pollution in healthy subjects. We intend to test the hypotheses that:
- Combustion derived nanoparticulate causes an acute impairment of endothelial vasomotor and fibrinolytic function in healthy volunteers.
- Exposure to combustion derived air pollution is associated with increased thrombus formation.
- Conditions
- Endothelial Dysfunction
- Being tested
- Forearm Vascular Study, Badimon Chamber
- Keywords
- Air Pollution, Particles, Particulate Matter, Vascular function, Endothelial function, Thrombosis
- Medical subject headings
- Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Forearm Vascular StudyProcedure or surgery
Also called BK, SNP, ACh
Forearm venous occlusion plethysmography to measure forearm blood flow during intra-arterial infusion of the vasodilators Verapamil (10-100 µg/min), bradykinin (100-1000 pmol/min), sodium nitroprusside (2-8 µg/min) and Acetylcholine (5-20 mg/min).
Badimon ChamberProcedure or surgery
Ex-vivo assessment of thrombus formation using Badimon Chamber
| Study group | Role | What they receive |
|---|---|---|
| Filtered Air Exposure | Experimental | 1 hour exposure to filtered air during intermittent exercise Receives: Procedure: Forearm Vascular Study; Procedure: Badimon Chamber |
| Diesel Exhaust Exposure | Experimental | 1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 during intermittent exercise Receives: Procedure: Forearm Vascular Study; Procedure: Badimon Chamber |
| Filtered Diesel Exposure | Experimental | 1 hour exposure to diesel exhaust with all particulates filtered out using teflon filter with intermittent exercise Receives: Procedure: Forearm Vascular Study; Procedure: Badimon Chamber |
| PALAS Exposure | Experimental | 1 hour exposure to pure carbon particles produced by PALAS generator during intermittent exercise Receives: Procedure: Forearm Vascular Study; Procedure: Badimon Chamber |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators
Measured: 6-8 hours after exposure
Secondary outcomes (7)
Ex-vivo thrombus formation assessed using the Badimon chamber
Measured: 6 hours after exposure
Arterial stiffness measured by radial artery tonometry
Measured: Before and after exposure
Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors
Measured: During and for 24 hours after exposure
Blood pressure
Measured: During and after exposure and during forearm study
Plasma t-PA and PAI concentrations following infusion of bradykinin
Measured: During forearm study
Plasma inflammatory markers IL-6, TNF-alpha, IL-1 and hsCRP
Measured: Before and after exposure
Platelet monocyte binding as measured by flow cytometry
Measured: After the exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2008 (estimated)
- Study startSep 2005
- Primary completionMar 2006
- Study completionMar 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Endothelial DysfunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Public Health and the Environment (RIVM)
- Investigators
- Nicholas L Mills, MB BCh MRCP, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00775099
- Sponsor's protocol ID
- 05/S1103/46
- Status last verified
- Oct 2008
- First submitted
- 16 Oct 2008
- Last updated
- 17 Oct 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
Mills NL, Tornqvist H, Robinson SD, Gonzalez M, Darnley K, MacNee W, Boon NA, Donaldson K, Blomberg A, Sandstrom T, Newby DE. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 2005 Dec 20;112(25):3930-6. doi: 10.1161/CIRCULATIONAHA.105.588962.
PubMed 16365212Langrish 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.
PubMed 24667535
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Combustion-Derived Air Pollution on Vascular Vasomotor and Fibrinolytic Function in Healthy Volunteers (Diesel Exposure)
- ClinicalTrials.gov ID
- NCT00775099
- Acronym / sponsor ID
- 05/S1103/46
- Conditions
- Endothelial Dysfunction
- Keywords
- Air Pollution, Particles, Particulate Matter, Vascular function, Endothelial function, Thrombosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- National Institute for Public Health and the Environment (RIVM)
- Study start
- Sep 2005
- Primary completion
- Mar 2006 (actual)
- Study completion
- Mar 2006 (actual)
- First posted
- 17 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Air pollution is a major cause of cardiovascular morbidity and mortality. The components of air pollution responsible and the mechanisms through which they might mediate these harmful effects remain only partially understood. The link between cardiovascular disease and air pollution is strongest for fine particulate matter. Fine particulate matter (PM) is produced from the combustion of fossil fuels with the most significant threat thought to be posed by small particles less than 10µm (PM 10) which can be inhaled into the lungs. We propose to identify the precise component of diesel exhaust that mediates the adverse cardiovascular effects using a carbon particle generator, and a particle concentrator. The aim of this study proposal is to assess the vascular effects of different types and components of air pollution in healthy subjects. We intend to test the hypotheses that:
- Combustion derived nanoparticulate causes an acute impairment of endothelial vasomotor and fibrinolytic function in healthy volunteers.
- Exposure to combustion derived air pollution is associated with increased thrombus formation.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Filtered Air Exposure | Experimental | Procedure: Forearm Vascular Study, Procedure: Badimon Chamber1 hour exposure to filtered air during intermittent exercise |
| Diesel Exhaust Exposure | Experimental | Procedure: Forearm Vascular Study, Procedure: Badimon Chamber1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 during intermittent exercise |
| Filtered Diesel Exposure | Experimental | Procedure: Forearm Vascular Study, Procedure: Badimon Chamber1 hour exposure to diesel exhaust with all particulates filtered out using teflon filter with intermittent exercise |
| PALAS Exposure | Experimental | Procedure: Forearm Vascular Study, Procedure: Badimon Chamber1 hour exposure to pure carbon particles produced by PALAS generator during intermittent exercise |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Healthy volunteers
Key exclusion criteria (12 listed)
- Current smokers
- Significant occupational exposure to air pollution
- History of lung disease
- Women of child-bearing potential
- Malignant arrhythmias
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Forearm Vascular StudyAlso: BK, SNP, AChForearm venous occlusion plethysmography to measure forearm blood flow during intra-arterial infusion of the vasodilators Verapamil (10-100 µg/min), bradykinin (100-1000 pmol/min), sodium nitroprusside (2-8 µg/min) and Acetylcholine (5-20 mg/min). | Procedure or surgery | Diesel Exhaust Exposure, Filtered Air Exposure, Filtered Diesel Exposure, PALAS Exposure |
| Badimon ChamberEx-vivo assessment of thrombus formation using Badimon Chamber | Procedure or surgery | Diesel Exhaust Exposure, Filtered Air Exposure, Filtered Diesel Exposure, PALAS Exposure |
Primary outcome
Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators
Time frame: 6-8 hours after exposure
7 secondary outcomes
Ex-vivo thrombus formation assessed using the Badimon chamber
Time frame: 6 hours after exposure
Arterial stiffness measured by radial artery tonometry
Time frame: Before and after exposure
Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors
Time frame: During and for 24 hours after exposure
Blood pressure
Time frame: During and after exposure and during forearm study
Plasma t-PA and PAI concentrations following infusion of bradykinin
Time frame: During forearm study
Plasma inflammatory markers IL-6, TNF-alpha, IL-1 and hsCRP
Time frame: Before and after exposure
Platelet monocyte binding as measured by flow cytometry
Time frame: After the exposure
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2008.
- Background: PubMed 16365212Mills NL, Tornqvist H, Robinson SD, Gonzalez M, Darnley K, MacNee W, Boon NA, Donaldson K, Blomberg A, Sandstrom T, Newby DE. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 2005 Dec 20;112(25):3930-6. doi: 10.1161/CIRCULATIONAHA.105.588962.
- Derived from this study: PubMed 24667535Langrish 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicholas L Mills, MB BCh MRCP principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Forearm Vascular Study and Badimon Chamber in people with Endothelial Dysfunction, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators (time frame: 6-8 hours after exposure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00775099, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2008.