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Effects of a Single Oral Dose of KETone Ester ON Exercise Performance in Patients With Chronic Heart Failure

Not Applicable
Completed
Conditions
Heart Failure With Reduced Ejection Fraction
Heart Failure
Interventions
Dietary Supplement: Ketone ester drink (DeltaG®, 500 mg/kg body weight)
Dietary Supplement: Taste-matched, isovolumic placebo drink
Registration Number
NCT05348460
Lead Sponsor
University Medical Center Groningen
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
15
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Placebo - Ketone treatmentTaste-matched, isovolumic placebo drinkPatients 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.
Ketone - Placebo treatmentTaste-matched, isovolumic placebo drinkPatients 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.
Ketone - Placebo treatmentKetone ester drink (DeltaG®, 500 mg/kg body weight)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.
Placebo - Ketone treatmentKetone ester drink (DeltaG®, 500 mg/kg body weight)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.
Primary Outcome Measures
NameTimeMethod
Phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations from baseline to maximum exerciseDuring study-visit

Rate and magnitude of change in PCr and Pi concentrations from baseline to maximum exercise.

Secondary Outcome Measures
NameTimeMethod
Intramuscular pHDuring study visit

Rates and magnitude of change in intramuscular pH during exercise and recovery

Maximal exercise performanceDuring study visit

Maximal exercise performance

Change in concentrations of beta-hydroxybutyrate and other metabolites before consumption of the supplemental drink, after consumption of the supplemental drink and after exerciseDuring 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

Rate and magnitude of change in PCr and Pi concentrations during recoveryDuring study visit

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)

Trial Locations

Locations (1)

University Medical Center Groningen

🇳🇱

Groningen, Netherlands

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