Cardiovascular Effects of Exposure to Ozone (MOSES)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by Health Effects Institute
Sponsor:
Collaborators:
New England Research Institutes
University of California, San Francisco
University of North Carolina, Chapel Hill
University of Rochester
Information provided by (Responsible Party):
Health Effects Institute
ClinicalTrials.gov Identifier:
NCT01487005
First received: December 1, 2011
Last updated: June 8, 2012
Last verified: June 2012
  Purpose

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.


Condition
Cardiovascular Injury

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Multicenter Ozone Study in Elderly Subjects

Resource links provided by NLM:


Further study details as provided by Health Effects Institute:

Primary Outcome Measures:
  • Change in endothelial function [ Time Frame: Baseline (16 hours before exposure) and 4 hours after exposure ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    measured with Holter monitor

  • Change in prothrombotic vascular state [ Time Frame: Baseline (17 hour before exposure) and 3.5 and 22 hours after exposure ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    from Holter monitor


Secondary Outcome Measures:
  • Change in markers of systemic inflammation [ Time Frame: Baseline (17 hour before exposure) and 3.5 and 22 hours after exposure ] [ Designated as safety issue: No ]
    Peripheral blood samples will be taken and stored as plasma for measurements of inflammatory markers

  • Change in lung function [ Time Frame: Baseline (0.2 hours before exposure) and 0.5, 3, and 22.5 hours after exposure ] [ Designated as safety issue: No ]
    Spirometry

  • Lung inflammation [ Time Frame: 22 hours after exposure ] [ Designated as safety issue: No ]
    A sputum sample will be obtained and stored for measurement of inflammatory mediators


Biospecimen Retention:   Samples With DNA

Blood


Estimated Enrollment: 90
Study Start Date: January 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
elderly subjects
Healthy

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:

  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.
  Eligibility

Ages Eligible for Study:   55 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Healthy elderly volunteers living in or around San Francisco, CA, Research Triangle Park, NC, and Rochester, NY

Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01487005

Contacts
Contact: Maria G Costantini, PhD 617-488-2302 mcostantini@healtheffects.org

Locations
United States, California
University of California at San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Hofer Wong    415-206-8951    howong@sfghoem.ucsf.edu   
Principal Investigator: John Balmes, MD         
United States, Massachusetts
New England Research Institutes, Inc. Active, not recruiting
Watertown, Massachusetts, United States, 02472
United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Erika Little    585-275-4163    erika_little@urmc.rochester.edu   
Principal Investigator: Mark Frampton, MD         
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Martha Almond    919-966-0759    martha_almond@med.unc.edu   
Principal Investigator: Philip Bromberg, MD         
Sponsors and Collaborators
Health Effects Institute
New England Research Institutes
University of California, San Francisco
University of North Carolina, Chapel Hill
University of Rochester
Investigators
Principal Investigator: Anne Stoddard, PhD New England Research Institutes
  More Information

No publications provided

Responsible Party: Health Effects Institute
ClinicalTrials.gov Identifier: NCT01487005     History of Changes
Other Study ID Numbers: 10-01-4
Study First Received: December 1, 2011
Last Updated: June 8, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Health Effects Institute:
ozone
air pollution
vascular function
cardiac function
inflammation

ClinicalTrials.gov processed this record on September 22, 2014