Combined Dietary Nitrate and Exercise Intervention in Peripheral Artery Disease: Protocol Rationale and Design

Journal article


Mary N Woessner, Mitch D VanBruggen, Carl F Pieper, Erin K O'Reilly, William E. Kraus and Jason D Allen. (2017). Combined Dietary Nitrate and Exercise Intervention in Peripheral Artery Disease: Protocol Rationale and Design. JMIR Research Protocols. 6(10), pp. 1-12. https://doi.org/10.2196/resprot.7596
AuthorsMary N Woessner, Mitch D VanBruggen, Carl F Pieper, Erin K O'Reilly, William E. Kraus and Jason D Allen
Abstract

Background:
Peripheral artery disease (PAD) is caused by atherosclerotic occlusions in the legs. It affects approximately 8-12 million people in the United States alone, one-third of whom suffer from intermittent claudication (IC), defined as ischemic leg pain that occurs with walking and improves with rest. Patients with IC suffer a markedly impaired quality of life and a high perception of disability. Improving pain-free walking time is a primary goal of rehabilitation in this population.

Objective:
The nitric oxide (NO)-PAD trial is designed to compare the effects that 12 weeks of supervised exercise training, in combination with a high inorganic nitrate-content (beetroot [BR] juice) beverage or placebo (PL) beverage, has on clinical outcomes of exercise and functional capacity in two groups of PAD+IC patients: exercise training plus beetroot (EX+BR) and exercise training plus placebo (EX+PL). The primary aims of this randomized controlled, double-blind pilot study are to determine group differences following 12 weeks of EX+BR versus EX+PL in the changes for (1) exercise capacity: pain-free walking time (claudication onset time, COT), peak walk time (PWT), and maximal exercise capacity (peak oxygen uptake, VO2peak) during a maximal-graded cardiopulmonary exercise test (max CPX) and (2) functional capacity: 6-minute walk (6MW) distance. The secondary aims will provide mechanistic insights into the exercise outcome measures and will include (1) gastrocnemius muscle oxygenation during exercise via near-infrared spectroscopy (NIRS); (2) gastrocnemius muscle angiogenesis: capillaries per unit area and per muscle fiber, and relative fraction of type I, IIa, IIb, and IId/x fibers; and (3) vascular health/function via brachial artery flow-mediated dilation, lower-limb blood flow via plethysmography, and pulse wave velocity and reflection.

Methods:
A total of 30 subjects between 40 and 80 years of age with PAD who are limited by IC will undergo exercise training 3 days per week for 12 weeks (ie, 36 sessions). They will be randomized to either the EX+BR or EX+PL group where participants will consume a beverage high in inorganic nitrate (4.2 mmol) or a low-nitrate placebo, respectively, 3 hours prior to each training session.

Results:
Data collection from this study has been completed and is in the process of analysis and write-up. While the study is too underpowered—EX+BR, n=11; EX+PL, n=13—to determine between-group differences in the primary outcomes of COT, PWT, and 6MW, preliminary observations are promising with Cohen d effect sizes of medium to large.

Conclusions:
Exercise training is currently the most effective therapy to increase functional capacity in PAD+IC. If the addition of inorganic nitrate to an exercise regimen elicits greater benefits, it may redefine the current standard of care for PAD+IC.

Year2017
JournalJMIR Research Protocols
Journal citation6 (10), pp. 1-12
PublisherJ M I R Publications, Inc.
ISSN1929-0748
Digital Object Identifier (DOI)https://doi.org/10.2196/resprot.7596
Publisher's version
License
File Access Level
Open
Publication process dates
Deposited14 May 2021
Permalink -

https://acuresearchbank.acu.edu.au/item/8w0y1/combined-dietary-nitrate-and-exercise-intervention-in-peripheral-artery-disease-protocol-rationale-and-design

Download files


Publisher's version
  • 49
    total views
  • 23
    total downloads
  • 2
    views this month
  • 1
    downloads this month
These values are for the period from 19th October 2020, when this repository was created.

Export as

Related outputs

Eating disorders are associated with increased risk of fall injury and fracture in Swedish men and women
Axelsson, K. F., Woessner, M. N., Litsne, H., Wheeler, M., Flehr, A., King, A. J., Kalén, M., Vandenput, L. and Lorentzon, M.. (2022). Eating disorders are associated with increased risk of fall injury and fracture in Swedish men and women. Osteoporosis International. 33(6), pp. 1347-1355. https://doi.org/10.1007/s00198-022-06312-2
Higher bone remodeling biomarkers are related to a higher muscle function in older adults : Effects of acute exercise
Smith, Cassandra, Hiam, Danielle, Tacey, Alexander, Lin, Xuzhu, Woessner, Mary, Zarekookandeh, Navabeh, Garnham, Andrew Peter, Chubb, Paul, Lewis, Joshua, Sim, Marc, Herrmann, Markus, Duque, Gustavo and Levinger, Itamar. (2022). Higher bone remodeling biomarkers are related to a higher muscle function in older adults : Effects of acute exercise. Bone. 165, pp. 1-10. https://doi.org/10.1016/j.bone.2022.116545
The Effects of Acute High-Intensity Interval Exercise and Hyperinsulinemic-Euglycemic Clamp on Osteoglycin Levels in Young and Middle-Aged Men
Bauer, Carlie, Tacey, Alexander, Garnham, Andrew Peter, Smith, Cassandra, Woessner, Mary, Lin, Xuzhu, Zarekookandeh, Navabeh, Hare, David, Lewis, Joshua, Parker, Lewan and Levinger, Itamar. (2022). The Effects of Acute High-Intensity Interval Exercise and Hyperinsulinemic-Euglycemic Clamp on Osteoglycin Levels in Young and Middle-Aged Men. JBMR Plus. 6(11), pp. 1-6. https://doi.org/10.1002/jbm4.10667
Effects of inorganic nitrate supplementation on cardiovascular function and exercise tolerance in heart failure
Ferguson, Scott K., Woessner, Mary N., Holmes, Michael J., Belbis, Michael D., Carlström, Mattias, Weitzberg, Eddie, Allen, Jason D. and Hirai, Daniel M.. (2021). Effects of inorganic nitrate supplementation on cardiovascular function and exercise tolerance in heart failure. Journal of Applied Physiology. 130(4), pp. 914-922. https://doi.org/10.1152/JAPPLPHYSIOL.00780.2020
Effects of Dietary Inorganic Nitrate Supplementation on Exercise Performance in Patients With Heart Failure: Protocol for a Randomized, Placebo-Controlled, Cross-Over Trial
Mary N Woessner, Itamar Levinger, Christopher J Neil, Cassandra Smith and Jason D Allen. (2018). Effects of Dietary Inorganic Nitrate Supplementation on Exercise Performance in Patients With Heart Failure: Protocol for a Randomized, Placebo-Controlled, Cross-Over Trial. JMIR Research Protocols. 7(4), pp. 1-12. https://doi.org/10.2196/resprot.8865
Dietary nitrate supplementation in cardiovascular health: an ergogenic aid or exercise therapeutic?
Mary N Woessner, Luke C McIlvenna, Joaquin Ortiz de Zevallos, Christopher J Neil and Jason D Allen. (2018). Dietary nitrate supplementation in cardiovascular health: an ergogenic aid or exercise therapeutic? American Journal of Physiology: Heart and Circulatory Physiology. 314(2), pp. 195-212. https://doi.org/10.1152/ajpheart.00414.2017
Beet the Best? Dietary inorganic nitrate to augment exercise training in lower extremity peripheral artery disease with intermittent claudication
Woessner, Mary, VanBruggen, Mitch D., Pieper, Carl F., Sloane, Richard, Kraus, William E., Gow, Andrew J. and Allen, Jason D.. (2018). Beet the Best? Dietary inorganic nitrate to augment exercise training in lower extremity peripheral artery disease with intermittent claudication. Circulation Research. 123(6), pp. 654 - 659. https://doi.org/10.1161/CIRCRESAHA.118.313131
The effects of beta-alanine supplementation on physical working capacity at heart rate threshold
Smith-Ryan, Abbie E., Woessner, Mary N., Melvin, Malia N., Wingfield, Hailee L. and Hackney, Anthony C.. (2014). The effects of beta-alanine supplementation on physical working capacity at heart rate threshold. Clinical Physiology and Functional Imaging. 34(5), pp. 397-404. https://doi.org/10.1111/cpf.12111
Reproducibility and validity of a-mode ultrasound for body composition measurement and classification in overweight and obese men and women
Smith-Ryan, Abbie E., Fultz, Sarah N., Melvin, Malia N., Wingfield, Hailee L. and Woessner, Mary N.. (2014). Reproducibility and validity of a-mode ultrasound for body composition measurement and classification in overweight and obese men and women. PLoS ONE. 9(3), pp. 1-8. https://doi.org/10.1371/journal.pone.0091750
Body composition assessment in overweight women : Validation of air displacement plethysmography
Wingfield, Hailee L., Smith-Ryan, Abbie E., Woessner, Mary N., Melvin, Malia N., Fultz, Sarah N. and Graff, Rachel M.. (2014). Body composition assessment in overweight women : Validation of air displacement plethysmography. Clinical Physiology and Functional Imaging. 34(1), pp. 72-76. https://doi.org/10.1111/cpf.12067