Heart Failure, SystolicNCT06009276
Associations Between the Microbiome, Skeletal Muscle Perfusion, and Fitness Status
An observational study of Heart Failure, Systolic and Heart Failure, Diastolic, run by University of Virginia at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Systolic, Heart Failure, Diastolic, Peripheral Arterial Disease
- Type of treatment
- Pill or oral medicine
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Aug 2023to Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
Study population: The population will include healthy individuals over the age of 18 years of either sex, or individuals with cardiovascular disease (heart failure, peripheral artery disease).
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UVA Student Health and Wellness Building
Charlottesville, Virginia, 22903
Jason D Allen, PhD, 434-243-3508, ja6af@virginia.edu
About this study
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
Read the 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, Systolic, Heart Failure, Diastolic, Peripheral Arterial Disease, Overweight and Obesity
- Medical subject headings
- Heart Failure, Systolic, Heart Failure, Diastolic, Peripheral Arterial Disease, Overweight, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. | |
| 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. | |
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oral Nitrate Reducing Capacity
Assessment of the oral microbiome's ability to reduce nitrate to nitrite. This will be measured through a swab on the dorsal surface of the tongue, an unstimulated saliva sample, and a rinse of a standard nitrate solution.
Measured: Baseline, 4-weeks, 12-weeks, 6-months
Secondary outcomes (1)
Aerobic Capacity
Peak aerobic capacity (VO2peak) will be assessed using a symptom-limited graded exercise test on a cycle ergometer.
Measured: Baseline, 4-weeks, 12-weeks, 6-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2023
- Study start30 Aug 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure, SystolicStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jason Allen, University of Virginia
- Investigators
- Jason D Allen, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06009276
- Sponsor's protocol ID
- HSR230229
- Status last verified
- Dec 2025
- First submitted
- 18 Aug 2023
- Last updated
- 24 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Associations Between the Microbiome, Skeletal Muscle Perfusion, and Fitness Status
- ClinicalTrials.gov ID
- NCT06009276
- Acronym / sponsor ID
- HSR230229
- Conditions
- Heart Failure, Systolic, Heart Failure, Diastolic, Peripheral Arterial Disease, Overweight and Obesity
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 30 Aug 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 24 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
| 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. |
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- The population will include healthy individuals over the age of 18 years of either sex, or individuals with cardiovascular disease (heart failure, peripheral artery disease).
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Oral Nitrate Reducing Capacity
Time frame: Baseline, 4-weeks, 12-weeks, 6-months
Assessment of the oral microbiome's ability to reduce nitrate to nitrite. This will be measured through a swab on the dorsal surface of the tongue, an unstimulated saliva sample, and a rinse of a standard nitrate solution.
1 secondary outcome
Aerobic Capacity
Time frame: Baseline, 4-weeks, 12-weeks, 6-months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jason D Allen, PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure, Systolic and Heart Failure, Diastolic, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Casey C Derella, PhD (6092476377, bxg7vn@virginia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oral Nitrate Reducing Capacity (time frame: Baseline, 4-weeks, 12-weeks, 6-months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2025.