Cardiovascular Effects of Exposure to Ozone

Cardiovascular Injury Clinical Trial

— MOSES  

Official title:

Multicenter Ozone Study in Elderly Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01487005
• Other study ID #: 10-01-4
• Status: Recruiting
• Phase: N/A
• First received: December 1, 2011
• Last updated: June 8, 2012
• Start date: January 2012
• Est. completion date: December 2014

Study information

• Verified date: June 2012
• Source: Health Effects Institute
• Contact: Maria G Costantini, PhD
• Phone: 617-488-2302
• Email: mcostantini[@]healtheffects.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical 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, endothelial dysfunction, and thrombosis.

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:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 55 Years to 70 Years

Eligibility

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)

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Cardiovascular Injury

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Rochester	Rochester	New York
United States	University of California at San Francisco	San Francisco	California
United States	New England Research Institutes, Inc.	Watertown	Massachusetts

Sponsors (5)

Lead Sponsor	Collaborator
Health Effects Institute	New England Research Institutes, University of California, San Francisco, University of North Carolina, Chapel Hill, University of Rochester

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in endothelial function	Brachail artey flow-mediated dilation and nitroglycerin-mediated dilation	Baseline (16 hours before exposure) and 4 hours after exposure	No
Primary	Change in heart rate variability	measured with Holter monitor	Baseline (0.5 hours before exposure) and 0.2, 2, and 21.5 after exposure	No
Primary	Change in prothrombotic vascular state	Peripheral blood samples will be taken and stored as plasma for measurement of von Willenbrand Factor antigen	Baseline (17 hour before exposure) and 3.5 and 22 hours after exposure	No
Primary	Change in cardiac repolarization	from Holter monitor	Baseline (0.5 hours before exposure) and 0.2, 2, and 21.5 after exposure	No
Secondary	Change in markers of systemic inflammation	Peripheral blood samples will be taken and stored as plasma for measurements of inflammatory markers	Baseline (17 hour before exposure) and 3.5 and 22 hours after exposure	No
Secondary	Change in lung function	Spirometry	Baseline (0.2 hours before exposure) and 0.5, 3, and 22.5 hours after exposure	No
Secondary	Lung inflammation	A sputum sample will be obtained and stored for measurement of inflammatory mediators	22 hours after exposure	No