Clinical trial NCT04908917: Reducing Air Pollution to Lower Blood Pressure
Official title: Reducing AIR Pollution Exposure to Lower Blood PRESSURE
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Mild Hypertension
Air Pollution Exposure
Lead sponsor: Wayne State University
Sponsor class: OTHER
First posted: 2021-06-01
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is designed as a randomized, double-blind, sham-controlled parallel limb clinical trial. Two-hundred participants will be recruited and randomly allocated into the intervention group (N=100) to use a PAC with a HEPA filter in the bedroom and the control group (N=100) with a sham PAC (no HEPA filter inside the container).
Primary purpose: TREATMENT

Brief summary: Fine particulate matter \<2.5 μm (PM2.5) air pollution is the fifth leading risk factor for global mortality. Mitigating the clinically significant blood pressure (BP) elevation from air pollution by reducing PM2.5 exposure will likely contribute to the reduction in cardiovascular disease-related mortality. Twin epidemics of air pollution and high BP converge in underserved urban communities (i.e., Detroit) and warrant immediate attention. Prior studies with short duration (a few days) showed indoor portable air cleaners (PACs) are a novel approach to reduce the health burden of both high BP and PM2.5. Trials over several weeks employing remote technologies with a large sample size of patients residing in their own homes in vulnerable urban communities are needed to demonstrate if the BP-reduction from PAC usage is sustainable in real-world settings. The investigators' specific aims are to 1) determine if compared to sham, active PAC use during 3 weeks can provide sustained reductions in home BP levels by reducing personal-level PM2.5 air pollution exposures in patients with mild high BP residing in vulnerable disadvantaged communities across Detroit and 2) explore clinical markers (e.g., age, sex, body mass index) that predict BP-responses to PAC intervention to better target at-risk populations in larger-scale trials and future real-world clinical settings. A randomized, double-blind, sham-controlled parallel limb trial of overnight bedroom PAC use versus sham with 200 Detroit community individuals with mild high BP will be conducted. Continuous bedroom PM2.5 levels and home BP will be measured throughout 28 days. PAC will be used in the bedroom before bedtime on the 7th day continuously for 21 days. The reduction of systolic BP (SBP) will be calculated for both the intervention and control groups and the significance will be compared using mixed-effects modeling with repeated measurements of SBP as the dependent variable and group (active vs sham PAC use) as the independent variable with a fixed-effect. Linear multiple regression modeling with SBP as the dependent variable and participant-level characteristics including body mass index, waist circumference, race, ethnicity, or sex as predictors will be explored. This study is expected to demonstrate a significant sustainable reduction in home SBP for active PAC vs sham use in this population with mildly high BP.

Detailed description: 1. Air pollution caused by fine particulate matter with aerodynamic diameter \<2.5 μm (PM2.5) is the fifth leading risk factor for global mortality,1,2 predominantly due to cardiovascular disease (CVD).3-5 While several mechanisms are responsible,4,6 PM2.5-induced elevations in blood pressure (BP) was identified as a key pathway.7-10 Short term (hours-days) PM2.5 exposures increase systolic BP (SBP) by 2-10 mmHg in a dose-dependent manner while longer term exposures (months-to-years) promote the onset of hypertension (HTN).7,11,12 Relevant mechanisms include systemic inflammation, autonomic and vascular dysfunction, and activation of the renin-angiotensinaldosterone system (RAAS).4,5,7 Recent estimates of annual PM2.5 mortality are 8.9 million globally, due in part to PM2.5-mediated HTN.1,13 Exposure to current levels of ambient PM2.5 in the U.S. is associated with elevated BP, increased CVD risk and an estimated 213,000 deaths annually.1 Given the billions of people impacted, PM2.5 is an independent (modifiable) HTN risk factor of global public health importance. Therefore, mitigating the clinically significant BP elevation from air pollution by reducing PM2.5 exposure will likely contribute to the reduction in CVD-related mortality.
2. HTN is the leading risk factor for global morbidity and mortality and a major cause of health disparities. Nearly 50% of US adults meet criteria (≥130/80 mm Hg) for HTN.14 Serious disparities persist such that underserved communities, including Detroit, have the highest prevalence of HTN and the poorest treatment success. Mounting evidence indicates that PM2.5 contributes to this epidemic of HTN,7-11 and that individuals in disadvantaged urban environments (e.g., Detroit) face higher concentrations of air pollutants.15-17 Low socioeconomic status communities are especially "vulnerable" (i.e., highly exposed) and "susceptible" (i.e., higher risk for adverse health effects) to air pollution.15,17,18 In Detroit, CV mortality has been shown to be jointly impacted by high PM2.5 levels and vulnerability to exposures in communities of color and lower socioeconomic status. The investigators' studies have shown that air pollutants in the city of Detroit are responsible for increasing BP. Hence, addressing the co-epidemics of PM2.5 exposure and cardiometabolic illnesses is not only an issue of public health importance but also of environmental justice for urban settings such as Detroit. Thus, the twin epidemics of air pollution and HTN converge in underserved urban communities (i.e., Detroit) and warrant immediate attention. The novel recruitment strategy using the Wayne State University (WSU) mobile health units (MHUs) directly reaches out to disadvantaged communities across Detroit so those disproportionally affected by PM2.5 and high BP can be enrolled.
3. Indoor portable air cleaners (PACs) are a novel approach to reduce the health burden of both HTN and PM2.5. In a meta-analysis of 10 PAC trials (n=604), it was shown that a ≈30-60% reduction in PM2.5 lowered SBP by ≈4 mm Hg over ≈13 days.19 In the investigators' trial of 40 nonsmokers living in urban senior housing,20 PACs lowered personal PM2.5 by ≈40% and morning SBP by 3.2 mmHg over 3 days, with greater reductions (≈8 mm Hg) in obese individuals. Emerging evidence shows that obesity and underlying cardiometabolic abnormalities play a mechanistic role in PM2.5-induced BP elevations and may underlie their susceptibility to PM2.5 and heightened BP-lowering responsiveness to PACs. This supports that populations commonly suffering from obesity, including African American hypertensives, may gain especially potent benefits from PACs. Trials over several weeks employing remote technologies with a large sample size of patients residing in their own homes in vulnerable urban communities are needed to demonstrate if the BP-reduction from PAC usage is sustainable in real-world settings. These are the features and innovations of the current study.

Prior studies in air pollution exposure intervention all have used physical contact methods with participants to assess exposure and measure BP. However, such direct contact and home visit methods to collect data during this COVID-19 pandemic becomes a challenge and unsafe for both investigators and study participants. Additionally, it costs more manpower and resources. Modern monitoring techniques, equipment and communication technologies provide data collection using a "low touch" method of remote monitoring of PM-reduction and home BP (HBP) lowering which is important in COVID era as well as to reduce patient burden and reduce patient follow-up. This will lend itself to be potentially greatly upscaled if patients can do all endpoints via remote technology. This study will be the first to test this technology as it applies to epidemiologic studies. This has never been tested before.

Additionally, studies in past used mixed populations with different BP levels and disease status. It is not known if reducing BP by reducing PM2.5 exposure using PACs also will work on people with mild HTN. In this study, the investigators' will focus specifically on people with mild HTN -the patients who actually need BP-lowering intervention for early treatment. This has not been looked at in this mild HTN population.

This study will serve as a pivotal trial to demonstrate that PACs are: 1) an effective method to lower PM2.5 exposure and SBP; and 2) a novel intervention to treat mild high BP and potentially reduce the cardiovascular effects of PM2.5. 3) The investigators' aim to show that novel low-touch remote methods are acceptable and reliable for assessing the benefits of air pollution interventions and that they could be expanded to thousand participants and benefit large number of vulnerable community members.

The current study has several key innovations and contributions. This will be the first PAC trial to: 1) Persist longer than a few days in intervention duration, allowing us to determine if BP reduction with PAC use is sustainable over a clinically relevant duration of 21 days of active use. 2) This trial is ≈ 5-fold larger than the earlier trial in Detroit in order to provide the most definitive evidence ("pivotal trial") and allow for testing of effect modifiers (e.g., obesity) in medium-risk populations with mild high BP most likely to benefit from a novel BP lowering intervention. 3) Leverage existing WSU MHUs to address environmental inequities for urban patients with high BP. 4) Employ mobile technologies and remote monitoring to capture home BP and PM2.5 levels via "low-touch" methods in a real-world community setting in patients vulnerable to the health effects of high BP and PM2.5 exposures.

The investigators hypothesize that 1) PAC use will reduce indoor exposure to PM2.5 which will subsequently reduce SBP. 2) This reduction in home BP will be sustainable over several weeks in people with mildly high BP. 3) The study can be conducted via "low touch" remote technology (using home BP and PM monitors). 4) This remote technology will be employable and acceptable to vulnerable members of disadvantaged communities across Detroit.

Primary Aim: To determine if compared to sham, active PAC use during clinically relevant periods can provide sustained reductions in HBP levels (over 21 days) by reducing personal-level fine particulate matter (PM2.5) air pollution exposures in patients with mildly high BP residing in vulnerable disadvantaged communities across Detroit.

Secondary Aim: To explore clinical biomarkers (age, sex, body mass index) that predict the BP-lowering response to PAC intervention to target at-risk populations in larger-scale interventions and future real-world clinical settings and future real-world clinical settings.

Eligibility criteria: Inclusion Criteria:

* Self-reported nonsmokers (for at least last year)
* Has own smartphone
* Systolic BP (SBP) at 120-145 mmHg
* Diastolic blood pressure (DBP) \<95 mmHg
* Has history of hypertension with ≤ 3 medications and stable without change in past 3 months
* If medications are used, there should be no change in dosage during the 28-day study period.

Exclusion Criteria:

* Living with an active smoker who smokes indoors
* Left upper arm circumference \>17 inches (measured by tape measure upon recruitment as needed as it makes the home BP device inaccurate)
* Pregnant
* Unable/unwilling to consent
* Established cardiovascular disease (CVD)
* Stage IV clinical kidney disease (CKD)
* Clear barrier to technology use (e.g., visual or hearing impairment)
* Lung disease requiring oxygen
* Cancer receiving treatment
* Diabetes
* COVID-19 infections
* Any condition where the investigators believe the risk of a mildly high BP above 130/80 mmHg may pose risk to the patient during the 28-day period of the study including but not limited to aortic aneurysms

Primary outcomes:
measure: Blood pressure change measured by blood pressure meter
timeFrame: 28 days (Day 1 to Day 28 of the 4-week study).
Secondary outcomes:
measure: Demographaic characteristics measured by a questionnaire
timeFrame: One-time measurement at baseline (Day 1 to Day 7)
measure: Body mass index (BMI)
timeFrame: One-time measurement (Day 1 to Day 7)
Other outcomes:
Locations:
Study officials:
affiliation: Wayne State University
name: Youcheng Liu, MD, ScD, MS, MPH
role: PRINCIPAL_INVESTIGATOR
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