Peripheral Arterial Disease
Conditions
Keywords
Dietary nitrate supplementation, Beetroot juice
Brief 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). 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.
Interventions
DRUGBeetroot juice
This beverage contains 0.3 g of inorganic nitrate per 70 ml container, and is bottled and supplied by James White Drinks (UK).
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).
Sponsors
David N. Proctor, PhD
Milton S. Hershey Medical Center
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with peripheral arterial disease (PAD) 2. Capable of giving informed consent 3. Men and women age 21- 85 years 4. Diagnosed with PAD (i.e., ankle-brachial index below 0.9) 5. Fontaine stage II or less - no pain while resting 6. Satisfactory history and physical exam
Exclusion criteria
1. Children 2. Pregnant or nursing women 3. Patients taking nitroglycerine or nitrate preparations 4. Patients taking phosphodiesterase inhibitors such as sildenafil or tadalafil 5. Patients taking proton pump inhibitors 6. Ejection fraction \< 40% 7. Uncontrolled hypertension 8. Uncontrolled diabetes 9. Myocardial infarction within past 6 months or unstable angina 10. Severe lung disease (i.e., on supplemental oxygen or frequently use rescue inhalers) 11. Abnormality in hemoglobin or hematocrit or methemoglobin 12. Impaired renal function 13. Impaired liver function 14. History or diagnosis of Barrett's esophagus 15. Known allergy to beetroot juice or lemon juice 16. Inability to walk on a treadmill at a moderate pace (2.0 miles/hour)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Treadmill Time | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Coronary Flow Velocity Response to Peak Plantar Flexion Exercise | 4 days after initiating daily ingestion of beetroot juice | 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. |
| Resting Blood Pressure | 4 to 6 days after initiating daily ingestion of beetroot juice | Resting mean arterial blood pressure (mmHg) obtained prior to the exercise treadmill test obtained using an automated arm blood pressure cuff. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORUrs A Leuenberger, MD
Penn State University
Participant flow
Pre-assignment details
13 participants were screened for eligibility. 2 participants were excluded due to not meeting inclusion criteria. 11 participants were randomized. A total of 11 participants finished the entirety of the study (n=0 dropped out of the study once randomized).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 64.5 years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
None listed