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

University Medical Center Groningen (UMCG)

Status: Completed

Conditions: Heart Failure; Heart Failure With Reduced Ejection Fraction

Treatments: Dietary Supplement: Ketone ester drink (DeltaG®, 500 mg/kg body weight); Dietary Supplement: Taste-matched, isovolumic placebo drink

Study type: Interventional

Funder types: Other

Identifiers

NCT05348460

201900710

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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15 participants in 2 patient groups

Ketone - Placebo treatment

Other group

Description:

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.

Treatment:

Dietary Supplement: Ketone ester drink (DeltaG®, 500 mg/kg body weight)

Dietary Supplement: Taste-matched, isovolumic placebo drink

Placebo - Ketone treatment

Other group

Description:

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.

Treatment:

Dietary Supplement: Ketone ester drink (DeltaG®, 500 mg/kg body weight)

Dietary Supplement: Taste-matched, isovolumic placebo drink