Heart Failure, Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
Heart Failure, Ketone Body, HFrEF, Skeletal Muscle Metabolism, Mitochondrial Ketone Oxidation, 31P MRS, Pi/Pcr
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.
Interventions
DIETARY_SUPPLEMENTKetone 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_SUPPLEMENTTaste-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.
Sponsors
Netherlands Heart Foundation
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind masking
Intervention model description
Randomized, double-blind, placebo-controlled cross-over design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations from baseline to maximum exercise | During study-visit | Rate and magnitude of change in PCr and Pi concentrations from baseline to maximum exercise. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate and magnitude of change in PCr and Pi concentrations during recovery | During 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) |
| Intramuscular pH | During study visit | Rates and magnitude of change in intramuscular pH during exercise and recovery |
| Maximal exercise performance | During 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 exercise | 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 |
Countries
Netherlands
Outcome results
None listed