Effects of a Single Oral Dose of KETone Ester ON Exercise Performance in Patients With Chronic Heart Failure (KETONE-HF)

In a randomized, double-blind, placebo-controlled cross-over design, subjects will either receive a supplemental drink containing a commercially available ketone ester (DeltaG®, 500 mg/kg body weight), or a taste matched, isovolumic placebodrink and will then perform the 31phosphorus Magnetic Resonance Spectroscopy (31P MRS) exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time receiving the other treatment.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Dietary supplement: Ketone ester drink (DeltaG®, 500 mg/kg body weight); Dietary supplement: Taste-matched, isovolumic placebo drink

Detailed Description

The goal of this study is to investigate if oral ketone supplementation stimulates mitochondrial ATP production and improves exercise performance in patients with chronic HF. In a randomized, double-blind, placebo-controlled cross-over design, subjects will either receive a supplemental drink containing a commercially available ketone ester (DeltaG®, 500 mg/kg body weight), or a taste matched, isovolumic placebodrink and will then perform the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time receiving the other treatment. Endpoints include rate and magnitude of change in phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations from baseline to maximum exercise, rate and magnitude of change in PCr and Pi concentrations during recovery, rates and magnitude of change in intramuscular pH during exercise and recovery, maximal exercise performance and change in concentrations of beta-hydroxybutyrate and other metabolites before consumption of the supplemental drink, after consumption of the supplemental drink and after exercise.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Chronic Heart Failure NYHA II - III
• LVEF ≤40%
• Stable for the last 1 month prior to the study

Exclusion Criteria:

• Age <18 years;
• Unable or unwilling to undergo exercise MRI (physical disabilities, claustrophobia);
• Unable to complete the exercise protocol during the screening visit according to the professional opinion of the investigators;
• Comorbidities which can influence study results such as muscular dystrophies, peripheral artery disease, diabetes mellitus, severe anaemia (defined as Hb ≤6 mmol/L);
• Pregnant/trying to get pregnant/breastfeeding during the period from the first exercise test until 4 weeks after the last exercise test);
• Absolute contra-indications to undergo MRI according to the current UMCG protocols and guidelines (e.g. non-conditional medical device, recent device implantation, incompatible ferromagnetic objects in the body).
• BMI < 16 kg/m2; BMI > 35 kg/m2
• Unable to understand study procedures;
• Unable or unwilling to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Ketone - Placebo treatment; Patients will first receive a supplemental drink containing a ketone ester before performing the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time after receiving the placebo treatment.	Dietary supplement: Ketone ester drink (DeltaG®, 500 mg/kg body weight); In a double blind fashion, subjects will receive a ketone ester drink ór a taste-matched, isovolumic placebo drink and will then perform the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time receiving the other treatment.; Dietary supplement: Taste-matched, isovolumic placebo drink; In a double blind fashion, subjects will receive a ketone ester drink ór a taste-matched, isovolumic placebo drink and will then perform the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time receiving the other treatment.
Other: Placebo - Ketone treatment; Patients will first receive a placebodrink before performing the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time after receiving the supplemental drink containing a ketone ester.	Dietary supplement: Ketone ester drink (DeltaG®, 500 mg/kg body weight); In a double blind fashion, subjects will receive a ketone ester drink ór a taste-matched, isovolumic placebo drink and will then perform the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time receiving the other treatment.; Dietary supplement: Taste-matched, isovolumic placebo drink; In a double blind fashion, subjects will receive a ketone ester drink ór a taste-matched, isovolumic placebo drink and will then perform the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time receiving the other treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations from baseline to maximum exercise	Rate and magnitude of change in PCr and Pi concentrations from baseline to maximum exercise.	During study-visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate and magnitude of change in PCr and Pi concentrations during recovery	Rate and magnitude of change in PCr and Pi concentrations during recovery of change in PCr and Pi is expressed as change in Pi/PCr (ΔPi/PCr)	During study visit
Intramuscular pH	Rates and magnitude of change in intramuscular pH during exercise and recovery	During study visit
Maximal exercise performance	Maximal exercise performance	During study visit
Change in concentrations of beta-hydroxybutyrate and other metabolites before consumption of the supplemental drink, after consumption of the supplemental drink and after exercise	Change in concentrations of beta-hydroxybutyrate and other metabolites before consumption of the supplemental drink, after consumption of the supplemental drink and after exercise	During study visit

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Netherlands Heart Foundation
• Investigators: Principal Investigator: Daan Westenbrink, MD PhD, Unversity Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Actual): July 1, 2023
• Study Completion (Actual): July 1, 2023

Study Registration Dates

• First Submitted: March 4, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 27, 2022

Study Record Updates

• Last Update Posted (Estimated): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Heart Failure; HFrEF; 31P MRS; Skeletal Muscle Metabolism; Ketone Body; Mitochondrial Ketone Oxidation; Pi/Pcr
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 201900710

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No