Multicenter Ozone Study in Elderly Subjects
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Health Effects Institute
- Enrollment
- 90
- Locations
- 4
- Primary Endpoint
- Change in heart rate variability
Study Overview
Brief 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.
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:
Study Design
- Study Type
- Observational
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 55 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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)
Outcomes
Primary Outcomes
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 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 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
Secondary Outcomes
- Change in markers of systemic inflammation(Baseline (17 hour before exposure) and 3.5 and 22 hours after exposure)
- Lung inflammation(22 hours after exposure)
- Change in lung function(Baseline (0.2 hours before exposure) and 0.5, 3, and 22.5 hours after exposure)