HealthyNCT00434005
Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans
A study testing N-acetylcysteine, ascorbate in people with Healthy, run by University of Washington at 1 site in United States.
Trial summary
Objectives: This proposal addresses the overall hypothesis that ambient fine particulate matter exerts cardiovascular health effects via alteration of endothelial homeostasis, through a mechanism mediated by oxidative stress. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- N-acetylcysteine, ascorbate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Aug 2010
- 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 18 to 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults aged 18-49.
Who cannot join
- Nonsmokers, no history of hypertension, asthma, diabetes, hypercholesterolemia, or other chronic conditions requiring ongoing medical care. No recent history of antioxidant, vitamin/mineral/botanical, or fatty acid supplementation beyond a daily multi-vitamin.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans - the Role of Oxidative Stress
Objectives: This proposal addresses the overall hypothesis that ambient fine particulate matter exerts cardiovascular health effects via alteration of endothelial homeostasis, through a mechanism mediated by oxidative stress. This project will use a controlled human inhalation exposure to diesel exhaust particulate (DEP) as a model to address the following objectives: 1) Determine whether exposure to inhaled DEP is associated with endothelial dysfunction in a concentration-related manner; 2) Determine whether exposure to inhaled DEP is associated with evidence of systemic oxidative stress; and 3) Determine whether antioxidant supplementation blunts the DEP effect on endothelial function.
Read the detailed description
OBJECTIVES Evidence of the cardiovascular health effects of both acute and chronic exposure to ambient fine particulate matter (PM) has continued to accumulate in epidemiologic and experimental studies, without a demonstrated coherent pathophysiologic explanation. At the same time, the role of endothelial homeostasis in the development and triggering of cardiovascular disease has become more clear and compelling. Importantly, oxidative stress has emerged as a potential link between these two developments: Oxidative stress is known to play a role in endothelial dysfunction and is exerted by components of PM, especially of PM from combustion products. Based on this we propose an overall hypothesis: Inhalation of combustion-derived particles impact cardiovascular health by impairing endothelial function, through mechanisms mediated by increased oxidative stress.
Diesel exhaust particulate (DEP), an important contributor to ambient fine PM, has been demonstrated to exert oxidative stress in experimental systems. We propose a series of experiments to explore whether human exposure to DEP results in alteration of endothelial homeostasis and evidence of oxidative stress, and whether an antioxidant regimen can blunt the effects on endothelial function.
The objectives of this proposed research are to address the following specific hypotheses:
- Human exposure to inhaled DEP (at concentrations approximating 0, 100, 200 μg PM2.5/m3 [PM less than 2.5 microns in aerodynamic diameter]) results in concentration-related alteration of endothelial homeostasis, as reflected in ultrasonographic measurement of the brachial artery, plasma markers of endothelial homeostasis (endothelin-1, ICAM-1 [intercellular adhesion molecule-1], e-selectin, nitric oxide metabolites nitrate [NO3-] and nitrite [NO2-], IL-6, and TNF-α), and markers of thrombosis associated with endothelial activation or injury (plasminogen activator inhibitor-1 [PAI-1], Von Willebrand's factor [VWF], and D-dimer).
- Human exposure to inhaled DEP at 200 µg PM2.5/m3 results in evidence of systemic oxidative stress as assessed by markers in plasma and urine (isoprostane F-2α).
- Reduction in oxidant stress by ascorbate and N-acetylcysteine supplementation blunts the effect of inhaled DEP on endothelial function, as determined by ultrasonographic assessment of the brachial artery, plasma markers of endothelial homeostasis, or markers of thrombosis associated with endothelial activation.
- Conditions
- Healthy
- Being tested
- N-acetylcysteine, ascorbate, Placebo
- Keywords
- Air pollution, diesel, antioxidant, oxidative stress, endothelial, HRV, BAR
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteine, ascorbateDrug
NAC: 600mg twice daily for the day prior to exposure and 1x pre-exposure Ascorbate: 500mg twice daily for 7 days prior to exposure
PlaceboDrug
matched appearance to acetylcysteine and ascorbate intervention
| Study group | Role | What they receive |
|---|---|---|
| Diesel Exhaust | Experimental | Not described Receives: Drug: N-acetylcysteine, ascorbate; Drug: Placebo |
| Filtered Air | Sham comparator | Not described Receives: Drug: N-acetylcysteine, ascorbate; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brachial artery caliber
Measured: Pre-exposure, immediate post-exposure
Secondary outcomes (3)
Brachial Artery Flow-Mediated Dilation
Measured: Post-Exposure
Plasma Endothelin-1
Measured: Post-exposure (adjusted for pre-exposure level)
Serum IL-6
Measured: Post-exposure (adjusted for pre-exposure level)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2007 (estimated)
- Study startJul 2008
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Joel Daniel Kaufman, University of Washington
- Investigators
- Joel D Kaufman, M.D., MPH, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00434005
- Sponsor's protocol ID
- 22969-D
- Other IDs
- R830954, R827355, MO1RR-00037, ES015915, ES013195
- Status last verified
- Jan 2013
- First submitted
- 25 Aug 2006
- Last updated
- 16 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Cosselman KE, Krishnan RM, Oron AP, Jansen K, Peretz A, Sullivan JH, Larson TV, Kaufman JD. Blood pressure response to controlled diesel exhaust exposure in human subjects. Hypertension. 2012 May;59(5):943-8. doi: 10.1161/HYPERTENSIONAHA.111.186593. Epub 2012 Mar 19.
PubMed 22431582
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans - the Role of Oxidative Stress
- ClinicalTrials.gov ID
- NCT00434005
- Acronym / sponsor ID
- 22969-D
- Conditions
- Healthy
- Keywords
- Air pollution, diesel, antioxidant, oxidative stress, endothelial, HRV, BAR
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Jul 2008
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 12 Feb 2007 (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.
Objectives: This proposal addresses the overall hypothesis that ambient fine particulate matter exerts cardiovascular health effects via alteration of endothelial homeostasis, through a mechanism mediated by oxidative stress. This project will use a controlled human inhalation exposure to diesel exhaust particulate (DEP) as a model to address the following objectives: 1) Determine whether exposure to inhaled DEP is associated with endothelial dysfunction in a concentration-related manner; 2) Determine whether exposure to inhaled DEP is associated with evidence of systemic oxidative stress; and 3) Determine whether antioxidant supplementation blunts the DEP effect on endothelial function.
Detailed description
OBJECTIVES Evidence of the cardiovascular health effects of both acute and chronic exposure to ambient fine particulate matter (PM) has continued to accumulate in epidemiologic and experimental studies, without a demonstrated coherent pathophysiologic explanation. At the same time, the role of endothelial homeostasis in the development and triggering of cardiovascular disease has become more clear and compelling. Importantly, oxidative stress has emerged as a potential link between these two developments: Oxidative stress is known to play a role in endothelial dysfunction and is exerted by components of PM, especially of PM from combustion products. Based on this we propose an overall hypothesis: Inhalation of combustion-derived particles impact cardiovascular health by impairing endothelial function, through mechanisms mediated by increased oxidative stress.
Diesel exhaust particulate (DEP), an important contributor to ambient fine PM, has been demonstrated to exert oxidative stress in experimental systems. We propose a series of experiments to explore whether human exposure to DEP results in alteration of endothelial homeostasis and evidence of oxidative stress, and whether an antioxidant regimen can blunt the effects on endothelial function.
The objectives of this proposed research are to address the following specific hypotheses:
- Human exposure to inhaled DEP (at concentrations approximating 0, 100, 200 μg PM2.5/m3 [PM less than 2.5 microns in aerodynamic diameter]) results in concentration-related alteration of endothelial homeostasis, as reflected in ultrasonographic measurement of the brachial artery, plasma markers of endothelial homeostasis (endothelin-1, ICAM-1 [intercellular adhesion molecule-1], e-selectin, nitric oxide metabolites nitrate [NO3-] and nitrite [NO2-], IL-6, and TNF-α), and markers of thrombosis associated with endothelial activation or injury (plasminogen activator inhibitor-1 [PAI-1], Von Willebrand's factor [VWF], and D-dimer).
- Human exposure to inhaled DEP at 200 µg PM2.5/m3 results in evidence of systemic oxidative stress as assessed by markers in plasma and urine (isoprostane F-2α).
- Reduction in oxidant stress by ascorbate and N-acetylcysteine supplementation blunts the effect of inhaled DEP on endothelial function, as determined by ultrasonographic assessment of the brachial artery, plasma markers of endothelial homeostasis, or markers of thrombosis associated with endothelial activation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diesel Exhaust | Experimental | Drug: N-acetylcysteine, ascorbate, Drug: Placebo |
| Filtered Air | Sham comparator | Drug: N-acetylcysteine, ascorbate, Drug: Placebo |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy adults aged 18-49.
Key exclusion criteria (1 listed)
- Nonsmokers, no history of hypertension, asthma, diabetes, hypercholesterolemia, or other chronic conditions requiring ongoing medical care. No recent history of antioxidant, vitamin/mineral/botanical, or fatty acid supplementation beyond a daily multi-vitamin.
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 |
|---|---|---|
| N-acetylcysteine, ascorbateNAC: 600mg twice daily for the day prior to exposure and 1x pre-exposure Ascorbate: 500mg twice daily for 7 days prior to exposure | Drug | Diesel Exhaust, Filtered Air |
| Placebomatched appearance to acetylcysteine and ascorbate intervention | Drug | Diesel Exhaust, Filtered Air |
Primary outcome
Brachial artery caliber
Time frame: Pre-exposure, immediate post-exposure
3 secondary outcomes
Brachial Artery Flow-Mediated Dilation
Time frame: Post-Exposure
Plasma Endothelin-1
Time frame: Post-exposure (adjusted for pre-exposure level)
Serum IL-6
Time frame: Post-exposure (adjusted for pre-exposure level)
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 16 Jan 2013.
- Derived from this study: PubMed 22431582Cosselman KE, Krishnan RM, Oron AP, Jansen K, Peretz A, Sullivan JH, Larson TV, Kaufman JD. Blood pressure response to controlled diesel exhaust exposure in human subjects. Hypertension. 2012 May;59(5):943-8. doi: 10.1161/HYPERTENSIONAHA.111.186593. Epub 2012 Mar 19.
- Controlled Exposure LaboratoryLink provided by the sponsor.
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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.
Joel D Kaufman, M.D., MPH principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing N-acetylcysteine, ascorbate in people with Healthy, run by University of Washington at 1 site in United States.
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 1 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 16 Jan 2013. 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 States. 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. Some participants in this study may receive a placebo. 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?
Brachial artery caliber (time frame: Pre-exposure, immediate post-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 NCT00434005, which also lists 1 linked publication.
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 16 Jan 2013.