Cardiovascular InjuryMOSESNCT01487005
Cardiovascular Effects of Exposure to Ozone
An observational study of Cardiovascular Injury, run by Health Effects Institute at 4 sites in United States.
Trial summary
The Multicenter Ozone Study in Elderly Subjects will investigate whether short-term exposure of elderly volunteers to ambient levels of ozone in a controlled exposure setting causes acute cardiovascular responses as assessed by changes in blood pressure, cardiac function, and systemic biomarkers of inflammation… Read more about this study
- Who is it for?
- Ages 55 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Injury
- How many people
- 90 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2012to Dec 2014
- Phase
- Observational
- 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 55 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy elderly volunteers living in or around San Francisco, CA, Research Triangle Park, NC, and Rochester, NY
Who may be able to join
- males and females of all ethnic backgrounds.
- Normal spirometry (FEV1 and FVC >75% of predicted and FEV1/FVC >0.65).
- Ability to complete the exposure exercise regimen chosen to induce a ventilation rate of 15 to 17 L/min/m2 without exceeding 80% of predicted maximal heart rate.
- Normal baseline 12-lead resting ECG, and absence of significant ST depression while performing the 15-minute required level of exercise targeted for the exposure period.
- Subjects must be able to avoid certain medication supplements listed for 1 week before the exposure.
Who cannot join
- Non-English speaking.
- Including, but not limited to as ascertained by the physicians: Subjects with chronic cardiovascular (such as ischemic heart disease) or respiratory (such as asthma or COPD) disease; diabetes, or other organ or system dysfunction; cerebrovascular disease; active psychiatric disorders that would interfere with the subject's ability to understand and participate in the study. Subjects who have tested positive for a disease that affects the immune system (such as HIV, lymphoma, leukemia) or current drug or alcohol abuse (defined as having more than 3 drinks per day or being unable to abstain from alcohol for 3 days).
- Subjects with atopy or allergic rhinitis will not be excluded as long as they do not require regular treatment with antihistamines or systemic steroids.
- Ever-smokers (smoked tobacco or marijuana during the last five years, or with history of >10 pack year for tobacco or > 1 joint year for marijuana, or living with a smoker who smokes inside the house).
- Subject having plasma cotinine level > 3ng/mL.
- BMI >35 or <18 (35 is the official cut off for class 1 obesity).
Show all 11Show fewer
- Hypertension (defined as blood pressure >140 systolic or >90diastolic) or on anti-hypertension medications other than diuretics.
- Pregnancy or nursing (breastfeeding).
- On the following medications: prednisone, statins, beta-blockers, anticoagulants, current hormonal therapy, tamoxifen. Subjects will not be asked to discontinue needed prescription medications for the purpose of this study. If any of these medications becomes necessary during the course of the study, the subjects will be excluded. Use of other medications will be considered on an individual basis.
- Subjects taking aspirin or PDE5 inhibitors must be willing to abstain from these medications during the week preceding each exposure.
- Occupational exposures (exposed to high levels of vapors, dust, gases, or fumes on an on-going basis)
Trial locations and contacts
4 sites in 1 country.
United States4 sites, 3 recruiting
- Recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Martha Almond, 919-966-0759, martha_almond@med.unc.edu
Philip Bromberg, MD
- Recruiting
University of Rochester
Rochester, New York, 14642
Erika Little, 585-275-4163, erika_little@urmc.rochester.edu
Mark Frampton, MD
- Recruiting
University of California at San Francisco
San Francisco, California, 94143
Hofer Wong, 415-206-8951, howong@sfghoem.ucsf.edu
John Balmes, MD
- Active, not recruiting
New England Research Institutes, Inc.
Watertown, Massachusetts, 02472
About this study
Official title: Multicenter Ozone Study in Elderly Subjects
The Multicenter Ozone Study in Elderly Subjects will investigate whether short-term exposure of elderly volunteers to ambient levels of ozone in a controlled exposure setting causes acute cardiovascular responses as assessed by changes in blood pressure, cardiac function, and systemic biomarkers of inflammation, endothelial dysfunction, and thrombosis.
Read the detailed description
This multicenter study will investigate whether short-term exposure of elderly volunteers to ambient levels of O3 in a controlled exposure setting while intermittently exercising causes acute cardiovascular responses. The study is based on the suppositions that: 1) elderly people are a susceptible group for cardiovascular effects; and 2) effects are more likely with exercise.
The study will involve approximately 90 healthy volunteers aged ≥55 and ≤70 who meet strict criteria for inclusion. They will be exposed for 3 hours to clean air, 0.07 ppm O3 (near the current NAAQS), and 0.12 ppm O3 (a level measured in several locations in the US). A suite of cardiovascular and pulmonary endpoints will be measured on the day before the exposure and up to 22 hours after the exposures. The study is being conducted at three centers using a common protocol and common SOPs. Most the endpoints will be analyzed by core laboratories to reduce the variability in the results. A Data Coordination and Analysis Center will assemble all the data generated by the three centers and conduct the statistical analyses on the combined data sets.
The study has 3 main objectives:
- To determine the relationship of altered autonomic balance (measured as changes in heart rate and heart rate variability (HRV)), cardiac arrhythmia, and repolarization and ozone exposure.
- To identify instances of altered systemic vascular function [measured as brachial artery flow-mediated dilation (FMD)without and with nitroglycerin (NTG) when exposed to ozone.
- To identify pro-thrombotic vascular state (measured as increase in von Willebrand factor antigen in blood - primary endpoints) when exposed to ozone.
Additional objectives include:
- To identify any increase in micro particle-associated tissues factor (measured as number of particles and tissue factor activity) and platelet activation) in ozone exposure.
- To identify if markers of systemic oxidative stress and inflammation and any correlation with the cardiovascular effects and degree of airway injury (measured as CC16) and airway inflammatory effects (neutrophils and cytokines in induced sputum) in ozone exposure.
- To determine if cardiovascular effects in ozone exposure are correlated with airway inflammatory effects, but not lung function effects.
- Conditions
- Cardiovascular Injury
- Keywords
- ozone, air pollution, vascular function, cardiac function, inflammation
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| elderly subjects | Healthy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in endothelial function
Brachail artey flow-mediated dilation and nitroglycerin-mediated dilation
Measured: Baseline (16 hours before exposure) and 4 hours after exposure
Change in heart rate variability
measured with Holter monitor
Measured: Baseline (0.5 hours before exposure) and 0.2, 2, and 21.5 after exposure
Change in prothrombotic vascular state
Peripheral blood samples will be taken and stored as plasma for measurement of von Willenbrand Factor antigen
Measured: Baseline (17 hour before exposure) and 3.5 and 22 hours after exposure
Change in cardiac repolarization
from Holter monitor
Measured: Baseline (0.5 hours before exposure) and 0.2, 2, and 21.5 after exposure
Secondary outcomes (3)
Change in markers of systemic inflammation
Peripheral blood samples will be taken and stored as plasma for measurements of inflammatory markers
Measured: Baseline (17 hour before exposure) and 3.5 and 22 hours after exposure
Change in lung function
Spirometry
Measured: Baseline (0.2 hours before exposure) and 0.5, 3, and 22.5 hours after exposure
Lung inflammation
A sputum sample will be obtained and stored for measurement of inflammatory mediators
Measured: 22 hours after exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2014 (estimated)
- Study completionDec 2014 (estimated)
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 Cardiovascular InjuryStudies 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Health Effects Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Carelon Research, University of California, San Francisco, University of North Carolina, Chapel Hill, University of Rochester
- Responsible party
- Sponsor
- Investigators
- Anne Stoddard, PhD, Principal investigator, Carelon Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01487005
- Sponsor's protocol ID
- 10-01-4
- Acronym
- MOSES
- Status last verified
- Jun 2012
- First submitted
- 1 Dec 2011
- Last updated
- 11 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Rich DQ, Thurston SW, Balmes JR, Bromberg PA, Arjomandi M, Hazucha MJ, Alexis NE, Ganz P, Zareba W, Thevenet-Morrison K, Koutrakis P, Frampton MW. Do Ambient Ozone or Other Pollutants Modify Effects of Controlled Ozone Exposure on Pulmonary Function? Ann Am Thorac Soc. 2020 May;17(5):563-572. doi: 10.1513/AnnalsATS.201908-597OC.
PubMed 32125874Arjomandi M, Balmes JR, Frampton MW, Bromberg P, Rich DQ, Stark P, Alexis NE, Costantini M, Hollenbeck-Pringle D, Dagincourt N, Hazucha MJ. Respiratory Responses to Ozone Exposure. MOSES (The Multicenter Ozone Study in Older Subjects). Am J Respir Crit Care Med. 2018 May 15;197(10):1319-1327. doi: 10.1164/rccm.201708-1613OC.
PubMed 29232153
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Ozone Study in Elderly Subjects
- ClinicalTrials.gov ID
- NCT01487005
- Acronym / sponsor ID
- MOSES / 10-01-4
- Conditions
- Cardiovascular Injury
- Keywords
- ozone, air pollution, vascular function, cardiac function, inflammation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Health Effects InstituteUniversity, hospital or other
- Collaborators
- Carelon Research, University of California, San Francisco, University of North Carolina, Chapel Hill, University of Rochester
- Study start
- Jan 2012
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 7 Dec 2011 (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.
The Multicenter Ozone Study in Elderly Subjects will investigate whether short-term exposure of elderly volunteers to ambient levels of ozone in a controlled exposure setting causes acute cardiovascular responses as assessed by changes in blood pressure, cardiac function, and systemic biomarkers of inflammation, endothelial dysfunction, and thrombosis.
Detailed description
This multicenter study will investigate whether short-term exposure of elderly volunteers to ambient levels of O3 in a controlled exposure setting while intermittently exercising causes acute cardiovascular responses. The study is based on the suppositions that: 1) elderly people are a susceptible group for cardiovascular effects; and 2) effects are more likely with exercise.
The study will involve approximately 90 healthy volunteers aged ≥55 and ≤70 who meet strict criteria for inclusion. They will be exposed for 3 hours to clean air, 0.07 ppm O3 (near the current NAAQS), and 0.12 ppm O3 (a level measured in several locations in the US). A suite of cardiovascular and pulmonary endpoints will be measured on the day before the exposure and up to 22 hours after the exposures. The study is being conducted at three centers using a common protocol and common SOPs. Most the endpoints will be analyzed by core laboratories to reduce the variability in the results. A Data Coordination and Analysis Center will assemble all the data generated by the three centers and conduct the statistical analyses on the combined data sets.
The study has 3 main objectives:
- To determine the relationship of altered autonomic balance (measured as changes in heart rate and heart rate variability (HRV)), cardiac arrhythmia, and repolarization and ozone exposure.
- To identify instances of altered systemic vascular function [measured as brachial artery flow-mediated dilation (FMD)without and with nitroglycerin (NTG) when exposed to ozone.
- To identify pro-thrombotic vascular state (measured as increase in von Willebrand factor antigen in blood - primary endpoints) when exposed to ozone.
Additional objectives include:
- To identify any increase in micro particle-associated tissues factor (measured as number of particles and tissue factor activity) and platelet activation) in ozone exposure.
- To identify if markers of systemic oxidative stress and inflammation and any correlation with the cardiovascular effects and degree of airway injury (measured as CC16) and airway inflammatory effects (neutrophils and cytokines in induced sputum) in ozone exposure.
- To determine if cardiovascular effects in ozone exposure are correlated with airway inflammatory effects, but not lung function effects.
Study design
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| elderly subjects | – | –Healthy |
Who may qualify
- Ages
- 55 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy elderly volunteers living in or around San Francisco, CA, Research Triangle Park, NC, and Rochester, NY
Key inclusion criteria (5 listed)
- males and females of all ethnic backgrounds.
- Normal spirometry (FEV1 and FVC >75% of predicted and FEV1/FVC >0.65).
- Ability to complete the exposure exercise regimen chosen to induce a ventilation rate of 15 to 17 L/min/m2 without exceeding 80% of predicted maximal heart rate.
- Normal baseline 12-lead resting ECG, and absence of significant ST depression while performing the 15-minute required level of exercise targeted for the exposure period.
- Subjects must be able to avoid certain medication supplements listed for 1 week before the exposure.
Key exclusion criteria (11 listed)
- Non-English speaking.
- Including, but not limited to as ascertained by the physicians: Subjects with chronic cardiovascular (such as ischemic heart disease) or respiratory (such as asthma or COPD) disease; diabetes, or other organ or system dysfunction; cerebrovascular disease; active psychiatric disorders that would interfere with the subject's ability to understand and participate in the study. Subjects who have tested positive for a disease that affects the immune system (such as HIV, lymphoma, leukemia) or current drug or alcohol abuse (defined as having more than 3 drinks per day or being unable to abstain from alcohol for 3 days).
- Subjects with atopy or allergic rhinitis will not be excluded as long as they do not require regular treatment with antihistamines or systemic steroids.
- Ever-smokers (smoked tobacco or marijuana during the last five years, or with history of >10 pack year for tobacco or > 1 joint year for marijuana, or living with a smoker who smokes inside the house).
- Subject having plasma cotinine level > 3ng/mL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in endothelial function
Time frame: Baseline (16 hours before exposure) and 4 hours after exposure
Brachail artey flow-mediated dilation and nitroglycerin-mediated dilation
Change in heart rate variability
Time frame: Baseline (0.5 hours before exposure) and 0.2, 2, and 21.5 after exposure
measured with Holter monitor
Change in prothrombotic vascular state
Time frame: Baseline (17 hour before exposure) and 3.5 and 22 hours after exposure
Peripheral blood samples will be taken and stored as plasma for measurement of von Willenbrand Factor antigen
Change in cardiac repolarization
Time frame: Baseline (0.5 hours before exposure) and 0.2, 2, and 21.5 after exposure
from Holter monitor
3 secondary outcomes
Change in markers of systemic inflammation
Time frame: Baseline (17 hour before exposure) and 3.5 and 22 hours after exposure
Change in lung function
Time frame: Baseline (0.2 hours before exposure) and 0.5, 3, and 22.5 hours after exposure
Lung inflammation
Time frame: 22 hours after exposure
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2012.
- Derived from this study: PubMed 32125874Rich DQ, Thurston SW, Balmes JR, Bromberg PA, Arjomandi M, Hazucha MJ, Alexis NE, Ganz P, Zareba W, Thevenet-Morrison K, Koutrakis P, Frampton MW. Do Ambient Ozone or Other Pollutants Modify Effects of Controlled Ozone Exposure on Pulmonary Function? Ann Am Thorac Soc. 2020 May;17(5):563-572. doi: 10.1513/AnnalsATS.201908-597OC.
- Derived from this study: PubMed 29232153Arjomandi M, Balmes JR, Frampton MW, Bromberg P, Rich DQ, Stark P, Alexis NE, Costantini M, Hollenbeck-Pringle D, Dagincourt N, Hazucha MJ. Respiratory Responses to Ozone Exposure. MOSES (The Multicenter Ozone Study in Older Subjects). Am J Respir Crit Care Med. 2018 May 15;197(10):1319-1327. doi: 10.1164/rccm.201708-1613OC.
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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.
Anne Stoddard, PhD principal investigator
Carelon Research
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Injury, run by Health Effects Institute at 4 sites 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 5 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 11 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maria G Costantini, PhD (617-488-2302, mcostantini@healtheffects.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in endothelial function (time frame: Baseline (16 hours before exposure) and 4 hours after exposure). The study lists 4 primary outcomes in all. 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 NCT01487005, 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 11 Jun 2012.