Ignite Creation Date:
2024-05-06 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 1:54 PM
Study NCT ID:
NCT04715568
Status:
RECRUITING
Last Update Posted:
2024-07-12
First Post:
2020-12-17
Brief Title:
Secondhand Tobacco Smoke and Cardiovascular Disease
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
Occult Cardiovascular Disease With Chronic Exposure to Secondhand Tobacco Smoke
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a double-blind randomized placebo-controlled crossover clinical trial of efficacy and safety of an FDA-approved angiotensin receptor blocker losartan to improve cardiopulmonary outcomes in individuals with pre-Chronic Obstructive Pulmonary Disease COPD due to prolonged exposure to secondhand tobacco smoke
Detailed Description:
Secondhand tobacco smoke SHS remains a major public health problemThis is important particularly as the generations that endured the highest amount of SHS exposure are aging which could potentially accentuate the SHS-related occult health problems that may have been previously too subtle to be recognized Although acute and subacute health effects of exposure to SHS have been studied its long-term consequences have been more difficult to examine in part due to challenges with exposure assessment Nonsmoking flight attendants FA who worked on commercial aircrafts before the enactment of the smoking ban were exposed to heavy SHS in aircraft cabin for many years in a range similar to the nicotine exposure burden experienced by light smokers The regularity of this intense exposure in the cabin work environment lends itself to relatively accurate SHS exposure quantification through employment history and makes the exposed FA a unique population in which the long-term health effects of previous exposure to SHS could be examined as a form of natural experiment that is also generalizable to other SHS exposed populations
Over the past several years the investigators recruited a nonsmoking cohort of FA with such history of cabin SHS exposure who had subclinical signs and symptoms of pulmonary disease Furthermore while the FA in this cohort had no history of known cardiovascular disease and were able to perform well on maximum effort exercise testing they had an abnormal cardiovascular hypertensive response to exercise HRE that was associated with their cabin SHS exposure Subtle abnormal cardiovascular response to exercise in the absence of overt disease such as what the investigators observed in this cohort has been described in other populations with likely subclinical disease and is suggested to be associated with impaired cardiovascular function with potential future adverse outcomes However the underlying mechanisms that contribute to these abnormal cardiovascular responses are unclear and the rationale for initiation of preventative medical interventions in this setting remains unproven Thus the nature and clinical significance of these subtle abnormalities demands further investigation
The hypothesis of this study is that
1 Prolonged exposure to secondhand tobacco smoke SHS even when remote is associated with occult cardiovascular disease as determined by a abnormal cardiac structure and function b abnormal vascular structure and function and c abnormal circulatory mediators which altogether generate a hypertensive response to exertion and limit exercise capacity
2 Management of hypertensive response to exercise HRE via blocking of the renin-angiotensin system using an angiotensin-converting enzyme ACE receptor blocker reduces the hypertensive response and improves exercise capacity proxies for long-term cardiovascular health outcomes
The investigators will investigate the above hypothesis through the following specific aims
Specific Aim 1- Determine whether hypertensive response to exercise HRE is associated with abnormal cardiac andor vascular structure and function in flight attendants FA with prolonged cabin SHS exposure but without overt cardiovascular disease The investigators will perform cardiac magnetic resonance imaging MRI to measure myocardial dimensions and function including left ventricular LV mass volume ejection fraction LVEF and diastolic function The investigators will also measure aortic stiffness by regional pulse wave velocity PWV measurement in the thoracic aorta from the MRI The investigators will then examine the associations of these outcomes with SHS exposure and HRE
Specific Aim 2- Determine whether HRE is associated with abnormal circulatory markers of cardiovascular disease in those with prolonged SHS exposure but without overt disease The investigators will examine subjects peripheral blood samples for circulatory markers of systemic inflammation vascular function and prothrombotic state including ACE C-reactive protein CRP endothelin-1 ET-1 P-selectin fibrinogen and von Willebrand Factor vWF Moreover the investigators will perform molecular phenotyping of peripheral blood monocytes an important culprit in atherogenesis using mass cytometry in search for a proinflammatory profile associated with cardiovascular disease The investigators will then examine the associations of these outcomes with HRE and SHS exposure
Specific Aim 3- Determine whether short-term treatment with an ACE receptor blocker Losartan improves HRE and exercise capacity in those with prolonged exposure to SHS but without overt cardiovascular disease The investigators will perform a placebocontrolled double-blind randomized controlled trial RCT in subjects with HRE but without known cardiovascular disease to determine the efficacy and safety of blocking the reninangiotensin system in reducing HRE and improving exercise capacity a proxy for improved cardiovascular health
Over the past several years the investigators recruited a nonsmoking cohort of FA with such history of cabin SHS exposure who had subclinical signs and symptoms of pulmonary disease Furthermore while the FA in this cohort had no history of known cardiovascular disease and were able to perform well on maximum effort exercise testing they had an abnormal cardiovascular hypertensive response to exercise HRE that was associated with their cabin SHS exposure Subtle abnormal cardiovascular response to exercise in the absence of overt disease such as what the investigators observed in this cohort has been described in other populations with likely subclinical disease and is suggested to be associated with impaired cardiovascular function with potential future adverse outcomes However the underlying mechanisms that contribute to these abnormal cardiovascular responses are unclear and the rationale for initiation of preventative medical interventions in this setting remains unproven Thus the nature and clinical significance of these subtle abnormalities demands further investigation
The hypothesis of this study is that
1 Prolonged exposure to secondhand tobacco smoke SHS even when remote is associated with occult cardiovascular disease as determined by a abnormal cardiac structure and function b abnormal vascular structure and function and c abnormal circulatory mediators which altogether generate a hypertensive response to exertion and limit exercise capacity
2 Management of hypertensive response to exercise HRE via blocking of the renin-angiotensin system using an angiotensin-converting enzyme ACE receptor blocker reduces the hypertensive response and improves exercise capacity proxies for long-term cardiovascular health outcomes
The investigators will investigate the above hypothesis through the following specific aims
Specific Aim 1- Determine whether hypertensive response to exercise HRE is associated with abnormal cardiac andor vascular structure and function in flight attendants FA with prolonged cabin SHS exposure but without overt cardiovascular disease The investigators will perform cardiac magnetic resonance imaging MRI to measure myocardial dimensions and function including left ventricular LV mass volume ejection fraction LVEF and diastolic function The investigators will also measure aortic stiffness by regional pulse wave velocity PWV measurement in the thoracic aorta from the MRI The investigators will then examine the associations of these outcomes with SHS exposure and HRE
Specific Aim 2- Determine whether HRE is associated with abnormal circulatory markers of cardiovascular disease in those with prolonged SHS exposure but without overt disease The investigators will examine subjects peripheral blood samples for circulatory markers of systemic inflammation vascular function and prothrombotic state including ACE C-reactive protein CRP endothelin-1 ET-1 P-selectin fibrinogen and von Willebrand Factor vWF Moreover the investigators will perform molecular phenotyping of peripheral blood monocytes an important culprit in atherogenesis using mass cytometry in search for a proinflammatory profile associated with cardiovascular disease The investigators will then examine the associations of these outcomes with HRE and SHS exposure
Specific Aim 3- Determine whether short-term treatment with an ACE receptor blocker Losartan improves HRE and exercise capacity in those with prolonged exposure to SHS but without overt cardiovascular disease The investigators will perform a placebocontrolled double-blind randomized controlled trial RCT in subjects with HRE but without known cardiovascular disease to determine the efficacy and safety of blocking the reninangiotensin system in reducing HRE and improving exercise capacity a proxy for improved cardiovascular health
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None