It has recently been demonstrated that the increase in ketone oxidation in the myocardium is protective and that ketone delivery to the heart can restore myocardial energetics (ref 9) Ketones are often referred to as efficient *super fuels* because…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Rate and magnitude of change in PCr and Pi concentrations from baseline to
maximum exercise. These parameters inform on the integrated homeostatic
performance of oxidative and glycolytic ATP synthetic networks in muscle during
exercise.
Secondary outcome
- Post-exercise recovery rate of PCr and Pi concentrations. These rates inform
on mitochondrial ATP synthetic function
- Rates and magnitude of change in intramuscular pH during exercise and
recovery. These parameters inform on the magnitude of anaerobic, glycolytic ATP
synthesis.
- Maximal exercise performance.
Background summary
Heart Failure (HF) remains a devastating disease that is characterized with
severe symptoms, frequent hospital admissions and a grim prognosis. HF
currently affects 10% of the European population over 60 years of age and this
number is expected to increase by 50% within the next decade, particularly
among women (ref 1,2) Furthermore, 75 % of HF patients die within 8 years of
the initial diagnosis, making the mortality for HF much higher than for most
types of cancer (ref 1,2). New strategies to treat or prevent HF are therefore
urgently needed.
Recent evidence from failing human and mouse hearts has suggested that the
reductions in carbohydrate and fatty acid metabolism are partially overcome by
a compensatory increase in the ketone body oxidation. Moreover, the cardiac
uptake of ketone bodies is increased in HF patients with both preserved and
reduced ejection fraction.
Study objective
It has recently been demonstrated that the increase in ketone oxidation in the
myocardium is protective and that ketone delivery to the heart can restore
myocardial energetics (ref 9) Ketones are often referred to as efficient *super
fuels* because ketone oxidation produces more net molecules of ATP per atom of
oxygen than glucose and fatty acidsis. An additional merit of stimulating
myocardial ketone oxidation in HF is that it does not influence the oxidation
rates of glucose or fatty acid and therefore provide a true supplemental
source of fuel.
Exercise intolerance is a hallmark of HF and is one of the earliest and most
debilitating consequences of this syndrome. The current study will test if a
simple sports drink containing ketones can improve exercise performance in HF
patients
Study design
We will use a randomized, double-blind, placebo-controlled cross over design.
Subjects will undergo the exercise MR examination twice, where they will be
randomized to receive either a ketone ester or a placebo drink and subsequently
undergo an exercise MR-spectroscopy study. After one to two weeks, subjects
will cross-over and the exercise MR protocol will be repeated, this time
receiving the other treatment
Intervention
ketone ester drink vs. placebo
Study burden and risks
The present study will provide insight into the change in oxidative skeletal
muscle metabolism in patients with HF. The study aims to determine whether an
oral dose of ketones can improve exercise performance in heart failure
patients. The single oral administration of this potentially powerful
nutritional compound will not be able to prevent or cure heart failure, but
will hopefully improve quality of life by extending exercise capacity short
term. Subjects do not directly benefit from participating in the present
study.
Hanzeplein 1
Groningen 9700RB
NL
Hanzeplein 1
Groningen 9700RB
NL
Listed location countries
Age
Inclusion criteria
HFrEF
- Chronic Heart Failure NYHA II - III
- LVEF<=40%
- Stable for the last 1 months prior to the study
HFpEF
- Chronic Heart Failure NYHA II - III
- HFpEF based on HFaPEFF score >= 5
- LVEF >= 45 %
- Stable for the last 1 month prior to the study
Exclusion criteria
HFrEF
- Age <18 years;
- Unable or unwilling to undergo exercise MRI (physical disabilities,
claustrophobia);
- VO2peak >80% of expected and or/a cycling time of <8 minutes on recent
exercise testing;
- Comorbidities which can influence study results such as muscular dystrophies,
peripheral artery disease, insulin dependent 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 > 40 kg/m2;
- Unable to understand study procedures;
- Unable or unwilling to provide informed consent.
HFpEF
- Age <18 years;
- Unable or unwilling to undergo exercise MRI (physical disabilities,
claustrophobia);
- VO2peak >80% of expected and or/a cycling time of <8 minutes on recent
exercise testing;
- Comorbidities which can influence study results such as muscular dystrophies,
peripheral artery disease, insulin dependent diabetes mellitus, severe anaemia
(defined as Hb <=6 mmol/L), hypertrophic cardiomyopathy with outflow tract
obstruction and/or moderate to severe heart valve disease;
- 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 > 40 kg/m2
- Estimated glomular filtration rate <30
- Unable to understand study procedures;
- Unable or unwilling to provide informed consent.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL72044.042.19 |