Peripheral Arterial DiseasePhase 2HeartBeetNCT02553733
Effect of Beetroot Juice on Coronary Blood Flow and Walking Performance in PAD
A Phase 2 study testing Beetroot juice in people with Peripheral Arterial Disease, run by David N. Proctor, PhD at 1 site in United States.
Trial summary
In this study the investigators will test the hypothesis that short-term consumption of inorganic nitrate (supplied in concentrated beetroot juice) enhances coronary blood flow responses, large artery hemodynamics, and leg oxygenation/exercise tolerance in patients with peripheral arterial disease (PAD). Read more about this study
- Who is it for?
- Ages 21 to 85 years
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- Beetroot juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to Feb 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with peripheral arterial disease (PAD)
- Capable of giving informed consent
- Men and women age 21- 85 years
- Diagnosed with PAD (i.e., ankle-brachial index below 0.9)
- Fontaine stage II or less - no pain while resting
- Satisfactory history and physical exam
Who cannot join
- Children
- Pregnant or nursing women
- Patients taking nitroglycerine or nitrate preparations
- Patients taking phosphodiesterase inhibitors such as sildenafil or tadalafil
- Patients taking proton pump inhibitors
- Ejection fraction < 40%
Show all 16Show fewer
- Uncontrolled hypertension
- Uncontrolled diabetes
- Myocardial infarction within past 6 months or unstable angina
- Severe lung disease (i.e., on supplemental oxygen or frequently use rescue inhalers)
- Abnormality in hemoglobin or hematocrit or methemoglobin
- Impaired renal function
- Impaired liver function
- History or diagnosis of Barrett's esophagus
- Known allergy to beetroot juice or lemon juice
- Inability to walk on a treadmill at a moderate pace (2.0 miles/hour)
Trial locations and contacts
1 site in 1 country.
United States1 site
Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: Effects of Dietary Nitrate Supplementation on Coronary Blood Flow and Walking Performance in Peripheral Arterial Disease
In this study the investigators will test the hypothesis that short-term consumption of inorganic nitrate (supplied in concentrated beetroot juice) enhances coronary blood flow responses, large artery hemodynamics, and leg oxygenation/exercise tolerance in patients with peripheral arterial disease (PAD). Understanding and improving blood flow regulation in the heart and skeletal muscles of patients with PAD is important because exercise triggers symptoms of leg pain and substantially raises blood pressure and myocardial demand in these patients.
Read the detailed description
Peripheral arterial disease (PAD) is a strong predictor of cardiovascular mortality and negatively affects functional capacity and quality of life for as many as 14 million patients in the U.S. alone. One open-label study showed that acute consumption of beetroot juice improved 6 min walk performance, reduced blood pressure, and enhanced leg muscle oxygenation in PAD patients. However, no studies have rigorously confirmed these findings in a double-blind manner, nor have the effects of this supplement been investigated (acutely or short-term) in the coronary circulation of PAD patients.
In addition to studying its effects on graded treadmill walking performance and consequent large artery vasodilation, the present study will examine the effects of short-term beetroot juice consumption (twice/day) on both coronary and leg vasodilator (graded calf flexion) and vasoconstrictor (isometric handgrip, voluntary apnea) responses in patients with PAD. Participants will randomly consume either nitrate-rich or nitrate-depleted beetroot juice with a 7 to 14 day wash-out period between. Effects of beetroot juice consumption on plasma nitrate, nitrite and methemoglobin will also be assessed.
- Conditions
- Peripheral Arterial Disease
- Being tested
- Beetroot juice, Beetroot juice placebo
- Keywords
- Dietary nitrate supplementation, Beetroot juice
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beetroot juiceDrug
Also called Beet-It Organic Shot
This beverage contains 0.3 g of inorganic nitrate per 70 ml container, and is bottled and supplied by James White Drinks (UK).
Beetroot juice placeboDrug
Also called Beet-It organic placebo
This beverage is identical in look and taste to the Beet-It organic shot, but has the nitrate removed. It is also bottled and supplied by James White Drinks (UK).
| Study group | Role | What they receive |
|---|---|---|
| Beetroot juice (Beet-It Organic Shot) | Active comparator | Subjects will consume 70 ml of beetroot juice (Beet-It Organic Shot) twice per day (morning, afternoon) for 5 to 7 days to assess the short term effects of this nitrate supplement on graded treadmill walking responses (day 4) and vasodilator/vasoconstrictor responses in the coronary and lower leg circulations (day 5 or 6 or 7). On both study visits, subjects will consume their morning dose 1 hour 45 min before experiments begin. Receives: Drug: Beetroot juice |
| Placebo Comparator: Beetroot juice (Beet-It Organic Shot) | Placebo comparator | Subjects will consume 70 ml of beetroot juice (Beet-It Organic Placebo) twice per day (morning, afternoon) for 5 to 7 days to assess the short term effects of this nitrate supplement on graded treadmill walking responses (day 4) and vasodilator/vasoconstrictor responses in the coronary and lower leg circulations (day 5 or 6 or 7). On both study visits, subjects will consume their morning dose 1 hour 45 min before experiments begin. Receives: Drug: Beetroot juice placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Treadmill Time
Peak treadmill time was determined using the Gardner treadmill protocol, measured as the number of seconds the participant was able to walk until they asked to stop the test due to leg fatigue.
Measured: 4 to 6 days after initiating daily ingestion of beetroot juice
Secondary outcomes (2)
Coronary Flow Velocity Response to Peak Plantar Flexion Exercise
Change in LAD coronary artery flow velocity, measured using transthoracic ultrasound, from baseline rest to peak plantar flexion exercise. Single leg plantar flexion exercise of the most symptomatic leg was performed at a rate of 20 contractions per minute, with increases in workload (1 kg) every minute until volitional fatigue, or until maximum exercise duration of 14 min was reached.
Measured: 4 days after initiating daily ingestion of beetroot juice
Resting Blood Pressure
Resting mean arterial blood pressure (mmHg) obtained prior to the exercise treadmill test obtained using an automated arm blood pressure cuff.
Measured: 4 to 6 days after initiating daily ingestion of beetroot juice
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2015 (estimated)
- Study startDec 2015
- Primary completionFeb 2020
- Study completionFeb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- David N. Proctor, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Milton S. Hershey Medical Center, Wake Forest University Health Sciences
- Responsible party
- Sponsor-investigator, David N. Proctor, PhD, Penn State University
- Investigators
- Urs A Leuenberger, MD, Principal investigator, Penn State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02553733
- Sponsor's protocol ID
- 00003242
- Acronym
- HeartBeet
- Status last verified
- Jul 2026
- First submitted
- 15 Sep 2015
- Last updated
- 13 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kim DJ, Gao Z, Luck JC, Brandt K, Miller AJ, Kim-Shapiro D, Basu S, Leuenberger U, Gardner AW, Muller MD, Proctor DN. Effects of short-term dietary nitrate supplementation on exercise and coronary blood flow responses in patients with peripheral artery disease. Front Nutr. 2024 Jul 3;11:1398108. doi: 10.3389/fnut.2024.1398108. eCollection 2024.
PubMed 39027664
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Dietary Nitrate Supplementation on Coronary Blood Flow and Walking Performance in Peripheral Arterial Disease
- ClinicalTrials.gov ID
- NCT02553733
- Acronym / sponsor ID
- HeartBeet / 00003242
- Conditions
- Peripheral Arterial Disease
- Keywords
- Dietary nitrate supplementation, Beetroot juice
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- David N. Proctor, PhDUniversity, hospital or other
- Collaborators
- Milton S. Hershey Medical Center, Wake Forest University Health Sciences
- Study start
- Dec 2015 (actual)
- Primary completion
- Feb 2020 (actual)
- Study completion
- Feb 2020 (actual)
- First posted
- 18 Sep 2015 (estimated)
- Results
- Posted 13 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study the investigators will test the hypothesis that short-term consumption of inorganic nitrate (supplied in concentrated beetroot juice) enhances coronary blood flow responses, large artery hemodynamics, and leg oxygenation/exercise tolerance in patients with peripheral arterial disease (PAD). Understanding and improving blood flow regulation in the heart and skeletal muscles of patients with PAD is important because exercise triggers symptoms of leg pain and substantially raises blood pressure and myocardial demand in these patients.
Detailed description
Peripheral arterial disease (PAD) is a strong predictor of cardiovascular mortality and negatively affects functional capacity and quality of life for as many as 14 million patients in the U.S. alone. One open-label study showed that acute consumption of beetroot juice improved 6 min walk performance, reduced blood pressure, and enhanced leg muscle oxygenation in PAD patients. However, no studies have rigorously confirmed these findings in a double-blind manner, nor have the effects of this supplement been investigated (acutely or short-term) in the coronary circulation of PAD patients.
In addition to studying its effects on graded treadmill walking performance and consequent large artery vasodilation, the present study will examine the effects of short-term beetroot juice consumption (twice/day) on both coronary and leg vasodilator (graded calf flexion) and vasoconstrictor (isometric handgrip, voluntary apnea) responses in patients with PAD. Participants will randomly consume either nitrate-rich or nitrate-depleted beetroot juice with a 7 to 14 day wash-out period between. Effects of beetroot juice consumption on plasma nitrate, nitrite and methemoglobin will also be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Beetroot juice (Beet-It Organic Shot) | Active comparator | Drug: Beetroot juiceSubjects will consume 70 ml of beetroot juice (Beet-It Organic Shot) twice per day (morning, afternoon) for 5 to 7 days to assess the short term effects of this nitrate supplement on graded treadmill walking responses (day 4) and vasodilator/vasoconstrictor responses in the coronary and lower leg circulations (day 5 or 6 or 7). On both study visits, subjects will consume their morning dose 1 hour 45 min before experiments begin. |
| Placebo Comparator: Beetroot juice (Beet-It Organic Shot) | Placebo comparator | Drug: Beetroot juice placeboSubjects will consume 70 ml of beetroot juice (Beet-It Organic Placebo) twice per day (morning, afternoon) for 5 to 7 days to assess the short term effects of this nitrate supplement on graded treadmill walking responses (day 4) and vasodilator/vasoconstrictor responses in the coronary and lower leg circulations (day 5 or 6 or 7). On both study visits, subjects will consume their morning dose 1 hour 45 min before experiments begin. |
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with peripheral arterial disease (PAD)
- Capable of giving informed consent
- Men and women age 21- 85 years
- Diagnosed with PAD (i.e., ankle-brachial index below 0.9)
- Fontaine stage II or less - no pain while resting
Key exclusion criteria (16 listed)
- Children
- Pregnant or nursing women
- Patients taking nitroglycerine or nitrate preparations
- Patients taking phosphodiesterase inhibitors such as sildenafil or tadalafil
- Patients taking proton pump inhibitors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Beetroot juiceAlso: Beet-It Organic ShotThis beverage contains 0.3 g of inorganic nitrate per 70 ml container, and is bottled and supplied by James White Drinks (UK). | Drug | Beetroot juice (Beet-It Organic Shot) |
| Beetroot juice placeboAlso: Beet-It organic placeboThis beverage is identical in look and taste to the Beet-It organic shot, but has the nitrate removed. It is also bottled and supplied by James White Drinks (UK). | Drug | Placebo Comparator: Beetroot juice (Beet-It Organic Shot) |
Primary outcome
Peak Treadmill Time
Time frame: 4 to 6 days after initiating daily ingestion of beetroot juice
Peak treadmill time was determined using the Gardner treadmill protocol, measured as the number of seconds the participant was able to walk until they asked to stop the test due to leg fatigue.
2 secondary outcomes
Coronary Flow Velocity Response to Peak Plantar Flexion Exercise
Time frame: 4 days after initiating daily ingestion of beetroot juice
Resting Blood Pressure
Time frame: 4 to 6 days after initiating daily ingestion of beetroot juice
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39027664Kim DJ, Gao Z, Luck JC, Brandt K, Miller AJ, Kim-Shapiro D, Basu S, Leuenberger U, Gardner AW, Muller MD, Proctor DN. Effects of short-term dietary nitrate supplementation on exercise and coronary blood flow responses in patients with peripheral artery disease. Front Nutr. 2024 Jul 3;11:1398108. doi: 10.3389/fnut.2024.1398108. eCollection 2024.
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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. This study is not recruiting at the moment.
Urs A Leuenberger, MD principal investigator
Penn State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Beetroot juice in people with Peripheral Arterial Disease, run by David N. Proctor, PhD 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 6 inclusion and 16 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: finished, as of the sponsor's last update on 13 Aug 2026. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak Treadmill Time (time frame: 4 to 6 days after initiating daily ingestion of beetroot juice). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02553733, which also lists 1 linked publication.
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 13 Aug 2026.