Dietary Nitrate Supplementation and Thermoregulation

NCT03506646 | Completed Results

• 1 other identifier: 0201-18-FB
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blinded, randomized, crossover design study to assess the effects of dietary nitrate supplementation (beetroot juice) on peripheral artery disease (PAD) patients (ages 50-85) diagnosed with Fontaine stage I or II PAD (as determined by vascular surgeon at UNMC). Exclusion criteria include: 1) experience severe claudication (leg pain) at rest or tissue loss due to PAD (Fontaine stage III and IV), 2) have limited walking capacity due to conditions other than PAD, 3) are already supplementing with a form of dietary nitrate, or 4) have an allergy to beetroot juice. Subjects will be required to visit the lab 3 times and will be randomized to receive either the supplement or the placebo for the 2nd and 3rd visits. There will be a washout period of 14 days between the 2nd and 3rd visits. Visit 1 will take approximately 2 hours and the 2nd/3rd visits will take approximately 1.5 hours. Total experimentation period will last approximately 15 days. Visit 1 will consist of non-invasive baseline testing including assessment of endothelial function (flow-mediated dilation by ultrasound imaging), maximal walking capacity (Gardner treadmill protocol), leg function (near-infrared spectroscopy, time to onset claudication, blood flow to lower extremities), and body core temperature (rectal thermometer). Visits 2 and 3 will require consumption of either the supplement or placebo. The same tests from the baseline measurements will be performed for visits 2 and 3. There will be a recommended fourth visit, albeit not required, to review study results.

Conditions

Peripheral Arterial Disease; Peripheral Artery Disease

Outcome Measures

Primary Outcomes (1)

• Brachial Artery Endothelial Function

  Endothelial function will be assessed using flow mediated dilation to measure vasodilation in the brachial artery (baFMD).

  Pre and post treatment

Secondary Outcomes (6)

• Leg Endothelial Function

  Pre and Post treatment

• Muscle Tissue Oxygenation

  2 days

• Physical Walking Capacity

  maximum of 14 minutes each day for 2 days

• Autonomic Nervous System Activity

  maximum of 60 minutes each day for 2 days

• Microvascular Function

  maximum of 30 minutes each day for 2 days

Study Arms (2)

Beetroot juice-Placebo

EXPERIMENTAL

Subjects will be tested on two different days, first day will be baseline and Beetroot juice and second day will be Placebo. Testing will take place forty-minutes after Beetroot juice/placebo intake. There will be a 2-week washout between testing days.

Dietary Supplement: Beet root juice

Placebo-Beetroot juice

EXPERIMENTAL

Subjects will be tested on two different days, first day will be baseline and Placebo and second day will be Beetroot juice. Testing will take place forty-minutes after placebo/beetroot juice intake. There will be a 2-week washout between testing days.

Dietary Supplement: Placebo

Interventions

Placebo DIETARY_SUPPLEMENT

Participants will be given a gelatin tablet to serve as the control condition. This will be a double-blinded, randomized, cross-over design to examine the effects of beetroot juice on endothelial function, leg function, and thermoregulation.

Placebo-Beetroot juice

Beet root juice DIETARY_SUPPLEMENT

Beet root juice serves as a mode of dietary nitrate supplementation. This will be a double-blinded, randomized, cross-over design to examine the effects of beetroot juice on endothelial function, leg function, and thermoregulation.

Beetroot juice-Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• be able to give written, informed consent
• demonstrate positive history of chronic claudication
• have a history of exercise-limiting claudication
• have an ankle/brachial index \< 0.90 at rest
• have a stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks.
• be between 50-85 years old

You may not qualify if:

• pain at rest (severe claudication) and/or tissue loss due to PAD (Fontaine stage III and IV)
• acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma
• limited walking capacity due to other conditions other than PAD
• a form of nitrate supplementation already included in their diet/regimen
• an allergy to beetroot juice

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska at Omaha

Omaha, Nebraska, 68182, United States

Location

Related Publications (12)

• Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Pavey TG, Wilkerson DP, Benjamin N, Winyard PG, Jones AM. Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise. Am J Physiol Regul Integr Comp Physiol. 2010 Oct;299(4):R1121-31. doi: 10.1152/ajpregu.00206.2010. Epub 2010 Aug 11.

  PMID: 20702806 BACKGROUND

• Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, MacAllister R, Hobbs AJ, Ahluwalia A. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension. 2008 Mar;51(3):784-90. doi: 10.1161/HYPERTENSIONAHA.107.103523. Epub 2008 Feb 4.

  PMID: 18250365 BACKGROUND

• Eggebeen J, Kim-Shapiro DB, Haykowsky M, Morgan TM, Basu S, Brubaker P, Rejeski J, Kitzman DW. One Week of Daily Dosing With Beetroot Juice Improves Submaximal Endurance and Blood Pressure in Older Patients With Heart Failure and Preserved Ejection Fraction. JACC Heart Fail. 2016 Jun;4(6):428-37. doi: 10.1016/j.jchf.2015.12.013. Epub 2016 Feb 10.

  PMID: 26874390 BACKGROUND

• Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation. 2004 Aug 10;110(6):738-43. doi: 10.1161/01.CIR.0000137913.26087.F0. Epub 2004 Jul 19.

  PMID: 15262830 BACKGROUND

• Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M, Privette G, Yim E, Kraus WE, Allen JD. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J Appl Physiol (1985). 2011 Jun;110(6):1582-91. doi: 10.1152/japplphysiol.00071.2011. Epub 2011 Mar 31.

  PMID: 21454745 BACKGROUND

• Bailey SJ, Varnham RL, DiMenna FJ, Breese BC, Wylie LJ, Jones AM. Inorganic nitrate supplementation improves muscle oxygenation, O(2) uptake kinetics, and exercise tolerance at high but not low pedal rates. J Appl Physiol (1985). 2015 Jun 1;118(11):1396-405. doi: 10.1152/japplphysiol.01141.2014. Epub 2015 Apr 9.

  PMID: 25858494 BACKGROUND

• Boegli Y, Gremion G, Golay S, Kubli S, Liaudet L, Leyvraz PF, Waeber B, Feihl F. Endurance training enhances vasodilation induced by nitric oxide in human skin. J Invest Dermatol. 2003 Nov;121(5):1197-204. doi: 10.1046/j.1523-1747.2003.12518.x.

  PMID: 14708626 BACKGROUND

• Lansley KE, Winyard PG, Fulford J, Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Gilchrist M, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled study. J Appl Physiol (1985). 2011 Mar;110(3):591-600. doi: 10.1152/japplphysiol.01070.2010. Epub 2010 Nov 11.

  PMID: 21071588 BACKGROUND

• Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf). 2007 Sep;191(1):59-66. doi: 10.1111/j.1748-1716.2007.01713.x. Epub 2007 Jul 17.

  PMID: 17635415 BACKGROUND

• Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol (1985). 2009 Oct;107(4):1144-55. doi: 10.1152/japplphysiol.00722.2009. Epub 2009 Aug 6.

  PMID: 19661447 BACKGROUND

• Leong P, Basham JE, Yong T, Chazan A, Finlay P, Barnes S, Bardin PG, Campbell D. A double blind randomized placebo control crossover trial on the effect of dietary nitrate supplementation on exercise tolerance in stable moderate chronic obstructive pulmonary disease. BMC Pulm Med. 2015 May 2;15:52. doi: 10.1186/s12890-015-0057-4.

  PMID: 25934631 BACKGROUND

• Wylie LJ, Kelly J, Bailey SJ, Blackwell JR, Skiba PF, Winyard PG, Jeukendrup AE, Vanhatalo A, Jones AM. Beetroot juice and exercise: pharmacodynamic and dose-response relationships. J Appl Physiol (1985). 2013 Aug 1;115(3):325-36. doi: 10.1152/japplphysiol.00372.2013. Epub 2013 May 2.

  PMID: 23640589 BACKGROUND

MeSH Terms

Conditions

Peripheral Arterial Disease

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Results Point of Contact

• Title: Song-Young Park
• Organization: University of Nebraska at Omaha

song-youngpark@unomaha.edu

402-554-3374

Study Officials

• Liz Pekas, MS

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1:1 randomized, cross-over, double-blinded

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: April 24, 2018
• Study Start: September 5, 2018
• Primary Completion: February 1, 2020
• Study Completion: December 15, 2022
• Last Updated: November 22, 2024
• Results First Posted: November 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)