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
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%
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- 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