Cardiovascular Effects of Exposure to Ozone

NCT ID: NCT01487005

Last Updated: 2012-06-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

90 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-01-31

Study Completion Date

2014-12-31

Brief Summary

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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

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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:

1. 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.
2. 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.
3. 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:

1. 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.
2. 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.
3. To determine if cardiovascular effects in ozone exposure are correlated with airway inflammatory effects, but not lung function effects.

Conditions

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Cardiovascular Injury

Study Design

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Study Time Perspective

PROSPECTIVE

Study Groups

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elderly subjects

Healthy

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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).
* 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)
Minimum Eligible Age

55 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Carelon Research

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role collaborator

University of Rochester

OTHER

Sponsor Role collaborator

Health Effects Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anne Stoddard, PhD

Role: PRINCIPAL_INVESTIGATOR

Carelon Research

Locations

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University of California at San Francisco

San Francisco, California, United States

Site Status RECRUITING

New England Research Institutes, Inc.

Watertown, Massachusetts, United States

Site Status ACTIVE_NOT_RECRUITING

University of Rochester

Rochester, New York, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Maria G Costantini, PhD

Role: CONTACT

617-488-2302

Facility Contacts

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Hofer Wong

Role: primary

415-206-8951

Erika Little

Role: primary

585-275-4163

Martha Almond

Role: primary

919-966-0759

References

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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.

Reference Type DERIVED
PMID: 32125874 (View on PubMed)

Arjomandi 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.

Reference Type DERIVED
PMID: 29232153 (View on PubMed)

Other Identifiers

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10-01-4

Identifier Type: -

Identifier Source: org_study_id

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