Associations Between the Microbiome, Skeletal Muscle Perfusion, and Fitness Status

NCT ID: NCT06009276

Last Updated: 2025-12-24

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 70 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-08-30
• Study Completion Date: 2026-12-31

Brief Summary

The purpose of the study is to determine associations between fitness status, bacteria in the mouth, and the blood flow to muscle. This study is trying to find out if fitness status impacts the bacteria that are present in the oral microbiome (environment in the mouth) or the ability of the body to send blood to the skeletal muscle.

Participants will complete all or some of the following:

• A mouth swab to assess the bacteria in their mouths.
• Produce a saliva sample into a tube.
• Cycle on a bike until you reach maximum effort.
• Undergo blood draws
• Wear a 24-hour non-invasive device that monitors blood pressure.
• Drink 70mL (1/3 of a cup) of concentrated beetroot juice once

Detailed Description

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Nitric oxide (NO) is a gaseous diatomic free-radical and is essential for a plethora of physiological functions involved in cardiometabolic health and CVD risk. NO bioavailability is associated with greater tissue perfusion, mitochondrial function, glucose regulation, and overall reduced CVD risk. The primary source of circulating NO is vascular endothelial nitric oxide synthase.

Unfortunately, the endothelium can be disrupted/damaged via a variety of CVD risk factors such as hypertension, smoking, hyperlipidemia, diabetes, inflammation, and hypercholesteremia. Disruption of the vascular endothelium and loss of bioavailable NO is a preliminary step in the progression of atherosclerosis and CVD. Decreased NO bioavailability and vascular dysfunction have been shown in a variety of clinical conditions including patients heart failure and peripheral artery disease (PAD).

Recently, an exogenous approach to increasing NO bioavailability via oral supplementation of inorganic nitrate (NO3-) has been utilized to increase NO bioavailability in various healthy and clinical populations. Briefly, inorganic NO3- is swallowed, absorbed into the circulation, and sequestered back into the salivary glands. NO3- is then secreted into the oral cavity, where bacteria containing nitrate reductase enzymes convert NO3- to nitrite (NO2-), which is again swallowed and absorbed into the circulation. NO2- in the plasma is then easily reduced to NO via non-enzymatic reactions.

This study aims to better elucidate the relationship between the oral microbiome abundance and diversity and NO3- to NO2- to NO conversion across a variety of subject populations ranging from healthy subjects to those with risk factors for CVD and people with diagnosed CVD. We also aim to examine the relationship between oral microbiome NO3- reduction and impaired skeletal muscle perfusion and exercise capacity as NO bioavailability plays a large role in these physiological processes.

The results of this study may allow us to better understand how novel interventions to modify the oral microbiome may improve cardiometabolic health and physical function in individuals with CVD and outline potential new therapeutic approaches.

The primary objective of this preliminary study is to compare the abundance and diversity of oral NO3- reducing bacteria in a variety of subjects with varying cardiometabolic health status and their ability to convert oral inorganic nitrate to nitrite measured in the saliva and plasma.

Conditions

Heart Failure, Diastolic; Peripheral Arterial Disease; Overweight and Obesity; Heart Failure, Systolic

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Heart Failure

Patients diagnosed with Heart Failure (HFrEF and HFpEF). Oral microbiome will be analyzed through tongue swabs, saliva samples, and a saliva rinse. Patients will undergo a maximal exercise test, blood draws, and vascular testing. Patients will have the option to participate in a supplementation assessment with concentrated beetroot juice.

No interventions assigned to this group

Peripheral Artery Disease

Patients diagnosed with Peripheral Artery Disease (PAD). Oral microbiome will be analyzed through tongue swabs, saliva samples, and a saliva rinse. Patients will undergo a maximal exercise test, blood draws, and vascular testing. Patients will have the option to participate in a supplementation assessment with concentrated beetroot juice.

No interventions assigned to this group

Healthy Controls

Individuals that are not diagnosed with cardiovascular disease. Oral microbiome will be analyzed through tongue swabs, saliva samples, and a saliva rinse. Patients will undergo a maximal exercise test, blood draws, and vascular testing. Patients will have the option to participate in a supplementation assessment with concentrated beetroot juice.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
• Subjects may be of either sex with age 18 years.

Exclusion Criteria

• Oral antibiotic use within previous four weeks
• Oral disease or poor oral health as determined by the Oral Health Questionnaire
• Using an antibacterial mouthwash or a mouthwash containing chlorhexidine and unwilling to discontinue use
• Tobacco smokers
• Pregnant or lactating females
• Hypersensitivity to any ultrasound contrast agent
• Inability to perform exercise
• Unable to communicate effectively in English to the study team.
• Diagnosis of chronic renal failure (GFR < 60 ml/min/1.73m)
• Subjects taking nitroglycerine (or inorganic nitrates), PDE-5 inhibitors (ex: Cialis, Viagra), and xanthine oxidase inhibitors (ex: Allopurinol).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Jason Allen

Professor of Kinesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jason D Allen, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

UVA Student Health and Wellness Building

Charlottesville, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Casey C Derella, PhD

Role: CONTACT

Phone: 6092476377

Email: bxg7vn@virginia.edu

Macy E Stahl, B.S.E.d

Role: CONTACT

Phone: 5719698323

Email: mes4hm@virginia.edu

Facility Contacts

Jason D Allen, PhD

Role: primary

Other Identifiers

HSR230229

Identifier Type: -

Identifier Source: org_study_id