Neuromuscular Fatigability in Individuals With Heart Failure

NCT06551012 | Not Yet Recruiting

• 1 other identifier: 340538
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

Brief Summary

Brief summary The aims of this project are to 1) characterise muscle fatigue in individuals with chronic heart failure during exercise involving a smaller and larger muscle mass (Part I), 2) to determine the effect of nitrate supplementation on muscle fatigue during large muscle mass exercise in individuals with chronic heart failure (Part II), 3) understand the impact of exercise intolerance on quality of life in individuals with chronic heart failure (Part III). The main questions it aims to answer are:

• Is muscle fatigue attenuated during exercise engaging a smaller vs larger muscle mass in individuals with chronic heart failure owing to lower central cardiopulmonary constraints?
• Can supplementation with nitrate-rich beetroot juice reduce muscle fatigue and/or accelerate post-exercise recovery of muscle function in response to whole body exercise in individuals with heart failure?
• What impact does exercise intolerance have on the lives of individuals with chronic heart failure? For Part I, researchers will compare muscle fatigue during single- and double-leg incremental cycling in individuals with chronic heart failure. For Part II, researchers will compare muscle fatigue in individuals with chronic heart failure during double-leg incremental cycling following a period of beetroot juice supplementation containing nitrate, or with a placebo drink consisting of beetroot juice with nitrate extracted. For Part III, semi-structured interviews will be conducted to investigate the symptoms associated with performing physical activity and on the impact of exercise intolerance on quality of life in individuals with chronic heart failure.

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

Exercise; Physiology; Fatigability

Outcome Measures

Primary Outcomes (1)

• Maximal voluntary contraction force

  Maximal voluntary contraction (MVC) force of the right knee extensor will be taken pre, during and post-exercise.

  3 years

Secondary Outcomes (15)

• Voluntary activation

  3 years

• Resting evoked twitch force

  3 years

• Electromyography

  3 years

• Time constant for recovery of muscle oxygen uptake

  3 years

• Microvascular responsiveness

  3 years

Study Arms (2)

Nitrate-rich beetroot juice

EXPERIMENTAL

Participants will consume 2 x 70 ml bottles of nitrate-rich beetroot juice for a 7 day period prior to exercise testing

Dietary Supplement: Nitrate-rich beetroot juice

Beetroot juice with nitrate extracted

PLACEBO COMPARATOR

Participants will consume 2 x 70 ml bottles of beetroot juice with nitrate extracted for a 7 day period prior to exercise testing

Dietary Supplement: Beetroot juice with nitrate extracted

Interventions

Nitrate-rich beetroot juice DIETARY_SUPPLEMENT

Participants will consume 2 x 70 ml bottles of nitrate-rich beetroot juice for a 7 day period prior to exercise testing

Nitrate-rich beetroot juice

Beetroot juice with nitrate extracted DIETARY_SUPPLEMENT

Participants will consume 2 x 70 ml bottles of beetroot juice with nitrate extracted for a 7 day period prior to exercise testing

Beetroot juice with nitrate extracted

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a left ventricular ejection fraction \< 40% who have been diagnosed for at least 3 months.
• Classified according to New York Heart Association (NYHA) class II-III.
• Clinically stable and receiving optimal medical treatment.
• Aged ≥ 45 years old.
• Ability to read, write and converse in English without the support of an interpreter.
• Willingness to undertake physical activity with no contraindications to physical activity and capable of performing activities of daily living independently, without the use of a walking aid.
• Able to provide written informed consent.

You may not qualify if:

• An electrically implanted device (e.g., pacemaker, left ventricular assist device).
• Uncontrolled cardiac arrhythmias, myocardial infarction, percutaneous coronary intervention and/or bypass graft surgery up to 3 months previously.
• Receiving antacids or proton pump, xanthine oxidase, or phosphodiesterase inhibitors which affect the reduction of nitrate to nitrite and nitrite to nitric oxide.
• Treated with organic nitrates (e.g., trinitroglycerin)
• Major multi-morbidity or other alternative diagnoses of no obvious acute and self-limiting cause (e.g., patients with a terminal diagnosis of cancer, patients in receipt of oxygen therapy or oxygen saturation at rest \<92%).
• Obesity (body mass index \> 30 kg/m2).
• Current smoker.
• Presented with severe symptoms requiring urgent assessment and stabilisation (e.g., breathlessness at rest, hypotension, confusion).
• Severe physical disability preventing them from functioning independently;
• Unable to provide informed consent.
• Currently taking part in any other study.

Sponsors & Collaborators

• Newcastle University: lead

Related Publications (8)

• Swank AM, Horton J, Fleg JL, Fonarow GC, Keteyian S, Goldberg L, Wolfel G, Handberg EM, Bensimhon D, Illiou MC, Vest M, Ewald G, Blackburn G, Leifer E, Cooper L, Kraus WE; HF-ACTION Investigators. Modest increase in peak VO2 is related to better clinical outcomes in chronic heart failure patients: results from heart failure and a controlled trial to investigate outcomes of exercise training. Circ Heart Fail. 2012 Sep 1;5(5):579-85. doi: 10.1161/CIRCHEARTFAILURE.111.965186. Epub 2012 Jul 6.

  PMID: 22773109 BACKGROUND

• McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.

  PMID: 34447992 BACKGROUND

• Poole DC, Hirai DM, Copp SW, Musch TI. Muscle oxygen transport and utilization in heart failure: implications for exercise (in)tolerance. Am J Physiol Heart Circ Physiol. 2012 Mar 1;302(5):H1050-63. doi: 10.1152/ajpheart.00943.2011. Epub 2011 Nov 18.

  PMID: 22101528 BACKGROUND

• Hepple RT. The role of O2 supply in muscle fatigue. Can J Appl Physiol. 2002 Feb;27(1):56-69. doi: 10.1139/h02-004.

  PMID: 11880691 BACKGROUND

• Weavil JC, Thurston TS, Hureau TJ, Gifford JR, Kithas PA, Broxterman RM, Bledsoe AD, Nativi JN, Richardson RS, Amann M. Heart failure with preserved ejection fraction diminishes peripheral hemodynamics and accelerates exercise-induced neuromuscular fatigue. Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H338-H351. doi: 10.1152/ajpheart.00266.2020. Epub 2020 Nov 8.

  PMID: 33164549 BACKGROUND

• Jones TW, Houghton D, Cassidy S, MacGowan GA, Trenell MI, Jakovljevic DG. Bioreactance is a reliable method for estimating cardiac output at rest and during exercise. Br J Anaesth. 2015 Sep;115(3):386-91. doi: 10.1093/bja/aeu560. Epub 2015 Feb 6.

  PMID: 25659999 BACKGROUND

• Jones AM, Ferguson SK, Bailey SJ, Vanhatalo A, Poole DC. Fiber Type-Specific Effects of Dietary Nitrate. Exerc Sport Sci Rev. 2016 Apr;44(2):53-60. doi: 10.1249/JES.0000000000000074.

  PMID: 26829247 BACKGROUND

• Coggan AR, Broadstreet SR, Mahmood K, Mikhalkova D, Madigan M, Bole I, Park S, Leibowitz JL, Kadkhodayan A, Thomas DP, Thies D, Peterson LR. Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction. J Card Fail. 2018 Feb;24(2):65-73. doi: 10.1016/j.cardfail.2017.09.004. Epub 2017 Sep 12.

  PMID: 28916479 BACKGROUND

MeSH Terms

Conditions

Motor Activity

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• Callum Brownstein, PhD

  Newcastle University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Callum Brownstein, PhD

CONTACT

+44 (0)191 208 6000; callum.brownstein@newcastle.ac.uk

Guy MacGowan, PhD, MD

CONTACT

(44) 0191 244 8425; guy.macgowan@nhs.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The study will be double-blinded, with participant and investigator unaware of the treatment arm
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer in Exercise Physiology

Model Details: Randomised, cross-over trial. Participants will perform exercise following consumption of nitrate-rich beetroot juice and beetroot juice with nitrate extracted

Study Record Dates

• First Submitted: July 25, 2024
• First Posted: August 13, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: 5 years