Secondhand Tobacco Smoke and Cardiovascular Disease

NCT04715568 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 20-30189
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Diseases; Hypertension

Keywords

Second Hand Tobacco Smoke

Outcome Measures

Primary Outcomes (4)

• Mean Left Ventricular Ejection Fraction (LVEF)

  LVEF will be measured using Magnetic Resonance Imaging (MRI) using General Electric 1.5 Tesla MRI system without gadolinium contrast. In accordance with the American College of Cardiology (ACC), results will be reported quantitatively and qualitatively as follows: Hyperdynamic = LVEF greater than 70%, Normal = LVEF 50% to 70% (midpoint 60%), Mild dysfunction = LVEF 40% to 49% (midpoint 45%), Moderate dysfunction = LVEF 30% to 39% (midpoint 35%), Severe dysfunction = LVEF less than 30%.

  Baseline, approximately 1 day

• Mean Aortic pulse wave velocity (PWV)

  Aortic pulse wave velocity (PWV) is a marker of aortic stiffness and will be measured (in meters/second) by regional PWV measurement in the thoracic aorta from the MRI (General Electric 1.5 Tesla MRI system without gadolinium contrast).

  Baseline, approximately 1 day

• Change in Prevalence of CD14++CD16-

  CD14++CD16- are markers of pro-inflammatory phenotypes that will be measured among peripheral blood monocytes using mass cytometry.

  Up to 10 weeks

• Change in Mean Peak Oxygen Consumption (VO2 Peak) Level

  VO2 Peak is the peak rate of oxygen consumption in milliliters per kilogram per minute (mL/(kg·min) measured during incremental exercise on a Cardio-Pulmonary Exercise Test (CPET). Patients are encouraged to exercise to their maximum endurance or until the nurse ends exercise due to symptoms like pain, dizziness, syncope, excessive dyspnea, or leg discomfort.

  Up to 10 weeks

Secondary Outcomes (15)

• Mean Left Ventricular Mass

  Baseline, approximately 1 day

• Mean Left Ventricular Volume

  Baseline, approximately 1 day

• Change in Mean Angiotensin Converting Enzyme (ACE) Level

  Up to 10 weeks

• Change in Mean C-Reactive Protein (CRP) Level

  At baseline assessment (V1); 4th week of V2 (placebo/losartan) treatment period; and 4th week of V3 (placebo/losartan) treatment period

• Change in Mean Endothelin-1 Level

  Up to 10 weeks

Study Arms (2)

Placebo then Losartan

EXPERIMENTAL

Placebo tablets will be administered for the first 4 weeks followed by a washout period of 2 weeks. After the washout period has been completed, losartan tablets will be administered for the next 4 weeks.

Drug: Losartan; Drug: Placebo

Losartan then Placebo

EXPERIMENTAL

Losartan tablets will be administered for the first 4 weeks followed by a washout period of 2 weeks. After the washout period has been completed, placebo tablets will be administered for the next 4 weeks.

Drug: Losartan; Drug: Placebo

Interventions

Losartan DRUG

50 mg tablets taken orally

Also known as: Cozaar, Angiotensin II Receptor Blocker, Antihypertensive

Losartan then Placebo; Placebo then Losartan

Placebo DRUG

Tablets taken orally

Also known as: Inactive drug

Losartan then Placebo; Placebo then Losartan

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be able to understand and provide informed consent.
• Adults \>= 40 years of age.
• Must have a history of occupational exposure to secondhand tobacco smoke for at least 5 years such as flight attendants who worked for airlines before the smoking ban on aircrafts went into effect or casino workers who worked at casinos with no smoke-free policies.
• Must have never smoked or have a remote history of light smoking defined as follows:
• Lifetime smoking history equivalent to \< 1 pack-year and
• No smoking history for \>= 20 years at the time of enrollment.

You may not qualify if:

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
• Subject is pregnant, breast-feeding, or plans to become pregnant.
• Current therapy with angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).
• Known intolerance to ACE inhibitor or ARB.
• History of angioedema.
• Conventional indication for ACE inhibitor or ARB (e.g., history of myocardial infarction, known cardiomyopathy).
• Blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic while standing or sitting.
• Known unilateral or bilateral renal artery stenosis higher than 70%.
• Renal insufficiency (Creatinine Clearance \<30 mL/min by Cockcroft-Gault calculation).
• Current regular use of NSAIDs defined as daily use on 5 or more days of the week for more than one month.
• Potassium supplementation or serum potassium level of 5.0 milliequivalents (mEq)/dL or higher at V1.
• Current use of a potassium sparing diuretic.
• History of clinically overt cardiovascular disease including: stable or unstable angina; chest discomfort and dyspnea with baseline exertion; symptomatic coronary artery disease (as defined by history of abnormal stress test; cardiac catheterization showing \>70% coronary artery stenosis; history of revascularization; pathologic Q waves on EKG); poorly controlled resting hypertension (SBP\>160/ DBP\>95); congestive heart failure (CHF) (as defined by left ventricular ejection fraction (LVEF) \<55%; physical exam findings of CHF; symptomatic pulmonary edema); significant (\>mild) valvular heart disease; congenital heart disease; cardiac arrhythmias including frequent premature atrial or ventricular contractions (\>5 per minute).
• History of clinically overt pulmonary disease that may interfere with study procedures, including: greater than mild asthma, COPD, emphysema, chronic interstitial lung disease, and pulmonary hypertension.
• Neuromuscular disorders or physical disability to perform exercise testing using an ergometer.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Flight Attendant Medical Research Institute: collaborator

Study Sites (1)

San Francisco Veterans' Affairs Medical Center

San Francisco, California, 94121, United States

RECRUITING

Related Links

• University of California, San Francisco (UCSF) website for Arjomandi Lab

MeSH Terms

Conditions

Cardiovascular Diseases; Hypertension

Interventions

Losartan; Angiotensin Receptor Antagonists; Antihypertensive Agents

Condition Hierarchy (Ancestors)

Vascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Cardiovascular Agents; Therapeutic Uses

Study Officials

• Mehrdad Arjomandi, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mehrdad Arjomandi, MD

CONTACT

(415)221-4810; mehrdad.arjomandi@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All investigators, research staff, and subjects, with the exception of the San Francisco Veteran's Administration (VA) Medical Center Research Pharmacist, will be blinded to the treatment.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind randomized placebo-controlled crossover clinical trial

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: January 20, 2021
• Study Start: March 30, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)