Ketones in Heart Failure - Effects on Cardiac Efficiency

Status Completed

Clinical Trial Summary

Ketones may have beneficial effects on myocardial metabolism and hemodynamics. In the present study, healthy test subjects and patients with heart failure with reduced ejections fraction will be investigated in a randomized cross-over design with ketone infusions and placebo. Myocardial efficiency and hemodynamics will be evaluated.

Clinical Trial Description

The prevalence of patients with heart failure and reduced ejection fraction (HFrEF) is 1-2%, and the lifetime risk of heart failure at age 55 years is approximately 30%. Despite advances in treatment, hospitalization rate and mortality remains high. It is well known that myocardial metabolism changes during development of HFrEF, and may contribute to contractile dysfunction. However, the myocardium can be considered an omnivore regarding substrate utilization, conferring an important adaptive property. Hence, it metabolizes either glucose, lipids, lactate, amino acids or ketones (3-hydroxybutyrate) depending on substrate availability, hormonal status and cardiac demands. These substrates differ with regard to myocardial energy efficiency (MEE) (cardiac work related to oxygen consumption). Since high MEE is associated with a better prognosis in HFrEF, manipulating substrate uptake could be a new treatment modality in heart failure patients.

Recently, it was shown that the human myocardium increases 3-hydroxybutyrate (3-OHB) metabolism during development of HFrEF. These changes may be beneficial as 3-OHB could increase myocardial efficiency and lower oxidative stress by scavenging free radicals. However, until now this has not been investigated in clinical trials, and the effect of 3-OHB on cardiac function, oxygen consumption and perfusion remains undetermined in HFrEF patients.

In the present study the investigators will evaluate whether elevated circulating 3-OHB affect myocardial oxygen consumption, MEE and perfusion in healthy subjects and patients with HFrEF, and whether 3-OHB affect hemodynamics and contractile function.

10 healthy test subjects and 20 HFrEF patients will be subjected to placebo and 3-OHB infusion in a randomized cross-over design. Acetate-PET, echocardiography and right sided heart catheterization will be applied. ;

Study Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT03073356
Study type	Interventional
Source	University of Aarhus
Contact
Status	Completed
Phase	Phase 2
Start date	March 17, 2017
Completion date	November 16, 2017

View Details

See also
Status	Clinical Trial	Phase
Withdrawn	`NCT03227393` - The Effect of Yoga on Cardiac Sympathetic Innervation Evaluated by I-123 mIBG	N/A
Recruiting	`NCT04528004` - Mechanistic Studies of Nicotinamide Riboside in Human Heart Failure	Early Phase 1
Recruiting	`NCT04703842` - Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Reduced Ejection Fraction	Phase 1/Phase 2
Recruiting	`NCT04522609` - Electrostimulation of Skeletal Muscles in Patients Listed for a Heart Transplant	N/A
Completed	`NCT05475028` - Network Medicine Approaches to Classify Heart Failure With PReserved Ejection Fraction by Signatures of DNA Methylation and Point-of-carE Risk calculaTors (PRESMET)
Not yet recruiting	`NCT05988749` - Digital Remote Home Monitoring for Heart Failure	N/A
Not yet recruiting	`NCT06240403` - Digoxin and Senolysis in Heart Failure and Diabetes Mellitus	Phase 2
Recruiting	`NCT04950218` - The Psoriasis Echo Study
Suspended	`NCT04701112` - Acute Hemodynamic Effects of Pacing the His Bundle in Heart Failure	N/A
Completed	`NCT03305692` - ECG Belt vs. Echocardiographic Optimization of CRT	N/A
Recruiting	`NCT05933083` - MCNAIR Study: coMparative effeCtiveness of iN-person and teleheAlth cardIac Rehabilitation	N/A
Enrolling by invitation	`NCT03903107` - The Fluoroless-CSP Trial Using Electroanatomic Mapping	N/A
Withdrawn	`NCT04872959` - TRANSFORM Heart Failure With Reduced Ejection Fraction	N/A
Completed	`NCT02920918` - Treatment of Diabetes in Patients With Systolic Heart Failure	Phase 4
Completed	`NCT02334891` - Kyoto Congestive Heart Failure Study
Recruiting	`NCT03553303` - Pharmacodynamic Effects of Sacubitril/Valsartan on Natriuretic Peptides, Angiotensin and Neprilysin	Phase 4
Recruiting	`NCT04083690` - Multi-lead ECG to Effectively Optimize Resynchronization Devices: New CRT Recipients	N/A
Recruiting	`NCT03830957` - Efficacy and Safety of Ivabradine to Reduce Heart Rate Prior to Coronary CT-angiography in Advanced Heart Failure: Comparison With β-Blocker	N/A
Recruiting	`NCT06121323` - Physiological Effects of Lactate in Individuals With Chronic Heart Failure	N/A
Completed	`NCT03351283` - Effect of Sodium Intake on Brain Natriuretic Peptide Levels in Patients With Heart Failure	N/A

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.