Dietary Nitrate for Heart Failure

NCT01682356 | Completed Phase 1 Results DMC

• 1 other identifier: BRJ_201111134
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine if nitrates in a food, in this case - beetroot juice (BRJ) - is efficacious in improving exercise tolerance and/or peak power in patients with heart failure. The investigators will also determine if BRJ improves blood pressure, exercise efficiency, vascular and muscle function, and whether blood levels of nitrates increase hourly for a total of 4 hours after BRJ ingestion. A secondary aim is to determine if BRJ-derived nitrates are still effective at 1, 2 and 4 weeks after starting treatment. A tertiary aim is to determine the variation in the 6 minute walk test. Subjects will answer a basic medical information sheet and undergo a 6-minute walk test. After at least a 48 hours rest, subjects will be asked to repeat the 6 minutes' walk. The investigators will (1) determine if BRJ (as compared to placebo) improves peak power output in heart failure patients and controls (at \~ 1½ to 2 hours after ingestion); (2) compare the changes in cardiac muscle (on average \~ 8-12 hours after) BRJ or placebo ingestion in patients who will be undergoing an left ventricle (LV) assist device placement for clinical purposes. (a cross-sectional study); (3) determine if BRJ decreases elevated pulmonary artery (PA) pressures or improves vascular and/or microvascular function (at \~ 1½ - 2 hours after ingestion) in patients who are already coming in for a PA catheter placement for clinical purposes; (4) compare the physiological changes after BRJ ingestion in non-heart failure control subjects with those of patients with heart failure. Endpoints measured at the same time points after ingestion. The investigators hypothesize (1) that patients with heart failure and controls will have improved exercise capacity and power at lower oxygen cost (and thereby greater efficiency) \~ 1½- 2 hours after ingesting beet juice (BRJ) than after ingesting placebo (beet juice without nitrates); (2) that patients with heart failure will have a greater physiologic response to BRJ than non-heart failure controls since the former have worse physiological function to start with; (3) that patients with high pulmonary artery pressures will have an improvement in the pressures after ingestion with BRJ; (4) that myocardial perfusion will be higher after BRJ ingestion than after placebo; (5) that cyclic guanosine monophosphate (cGMP) levels will be increased in left ventricle assist device (LVAD) samples after BRJ ingestion compared with placebo.

Conditions

Heart Failure; Hypertension, Pulmonary

Keywords

heart failure; hypertension, pulmonary; oxygen consumption; exercise tolerance

Outcome Measures

Primary Outcomes (1)

• Maximal Knee Extensor Power

  Maximal power of the quadriceps muscle group as measured using isokinetic dynamometry

  2-3 h after acute dose of beetroot juice containing or essentially devoid of nitrate

Secondary Outcomes (1)

• VO2peak

  2-3 h after acute dose of beetroot juice containing or essentially devoid of nitrate

Other Outcomes (25)

• Baseline Plasma Nitrate

  0 h

• Plasma Nitrate @ 1 h

  1 h

• Plasma Nitrate @ 2 h

  2 h

Study Arms (2)

Beetroot juice without nitrate

PLACEBO COMPARATOR

Patients will be studied before and after ingestion of beetroot juice without nitrate

Dietary Supplement: Beetroot juice

Beetroot juice with nitrate

ACTIVE COMPARATOR

Patients will be studied before and after ingestion of beetroot juice with nitrate.

Dietary Supplement: Beetroot juice

Interventions

Beetroot juice DIETARY_SUPPLEMENT

double-blind placebo-controlled cross-over study

Also known as: Beet It

Beetroot juice with nitrate; Beetroot juice without nitrate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women will have a history of heart failure (and/or pulmonary hypertension for PA catheter substudy).
• Age \> or = 18 y and controls of the same age range without heart failure.

You may not qualify if:

• Age \< 18 y.
• Those taking phosphodiesterase inhibitors (e.g., Viagra) will be excluded, as these can potentiate NO effects.
• Those taking proton pump inhibitors, antacids, or xanthine oxidase inhibitors will be excluded as these can affect reduction of nitrate (NO3-) and nitrite (NO2-) to nitric oxide (NO).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• The Foundation for Barnes-Jewish Hospital: collaborator

Study Sites (2)

Indiana University Purdue University Indianapolis

Indianapolis, Indiana, 46202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (11)

• Masschelein E, Van Thienen R, Wang X, Van Schepdael A, Thomis M, Hespel P. Dietary nitrate improves muscle but not cerebral oxygenation status during exercise in hypoxia. J Appl Physiol (1985). 2012 Sep 1;113(5):736-45. doi: 10.1152/japplphysiol.01253.2011. Epub 2012 Jul 5.

  PMID: 22773768 BACKGROUND

• Hobbs DA, Kaffa N, George TW, Methven L, Lovegrove JA. Blood pressure-lowering effects of beetroot juice and novel beetroot-enriched bread products in normotensive male subjects. Br J Nutr. 2012 Dec 14;108(11):2066-74. doi: 10.1017/S0007114512000190. Epub 2012 Mar 14.

  PMID: 22414688 BACKGROUND

• Cermak NM, Gibala MJ, van Loon LJ. Nitrate supplementation's improvement of 10-km time-trial performance in trained cyclists. Int J Sport Nutr Exerc Metab. 2012 Feb;22(1):64-71. doi: 10.1123/ijsnem.22.1.64.

  PMID: 22248502 BACKGROUND

• Vanhatalo A, Fulford J, Bailey SJ, Blackwell JR, Winyard PG, Jones AM. Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia. J Physiol. 2011 Nov 15;589(Pt 22):5517-28. doi: 10.1113/jphysiol.2011.216341. Epub 2011 Sep 12.

  PMID: 21911616 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

• Ferreira LF, Behnke BJ. A toast to health and performance! Beetroot juice lowers blood pressure and the O2 cost of exercise. J Appl Physiol (1985). 2011 Mar;110(3):585-6. doi: 10.1152/japplphysiol.01457.2010. Epub 2010 Dec 23. No abstract available.

  PMID: 21183624 BACKGROUND

• 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

• Wilkerson DP, Hayward GM, Bailey SJ, Vanhatalo A, Blackwell JR, Jones AM. Influence of acute dietary nitrate supplementation on 50 mile time trial performance in well-trained cyclists. Eur J Appl Physiol. 2012 Dec;112(12):4127-34. doi: 10.1007/s00421-012-2397-6. Epub 2012 Apr 20.

  PMID: 22526247 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

• Tawa M, Nagata R, Sumi Y, Nakagawa K, Sawano T, Ohkita M, Matsumura Y. Preventive effects of nitrate-rich beetroot juice supplementation on monocrotaline-induced pulmonary hypertension in rats. PLoS One. 2021 Apr 8;16(4):e0249816. doi: 10.1371/journal.pone.0249816. eCollection 2021.

  PMID: 33831045 DERIVED

• Coggan AR, Leibowitz JL, Spearie CA, Kadkhodayan A, Thomas DP, Ramamurthy S, Mahmood K, Park S, Waller S, Farmer M, Peterson LR. Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial. Circ Heart Fail. 2015 Sep;8(5):914-20. doi: 10.1161/CIRCHEARTFAILURE.115.002141. Epub 2015 Jul 15.

  PMID: 26179185 DERIVED

MeSH Terms

Conditions

Heart Failure; Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases

Limitations and Caveats

Due to restrictions on research resulting from the COVID-19 pandemic, many outcome measures/planned substudies were not completed.

Results Point of Contact

• Title: Linda R. Peterson, MD
• Organization: Washington University School of Medicine

lpeterso@wustl.edu

314-362-4577

Study Officials

• Linda R Peterson, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Andrew R Coggan, PhD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2012
• First Posted: September 10, 2012
• Study Start: January 1, 2012
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: December 4, 2024
• Results First Posted: December 4, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)