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Ketones in Heart Failure - Effects on Cardiac Efficiency

NCT ID: NCT03073356

Last Updated: 2017-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-17

Study Completion Date

2017-11-16

Brief Summary

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Ketones may have beneficial effects on myocardial metabolism and hemodynamics. In the present study, healthy test subjects and patients with heart failure with reduced ejections fraction will be investigated in a randomized cross-over design with ketone infusions and placebo. Myocardial efficiency and hemodynamics will be evaluated.

Detailed Description

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The prevalence of patients with heart failure and reduced ejection fraction (HFrEF) is 1-2%, and the lifetime risk of heart failure at age 55 years is approximately 30%. Despite advances in treatment, hospitalization rate and mortality remains high. It is well known that myocardial metabolism changes during development of HFrEF, and may contribute to contractile dysfunction. However, the myocardium can be considered an omnivore regarding substrate utilization, conferring an important adaptive property. Hence, it metabolizes either glucose, lipids, lactate, amino acids or ketones (3-hydroxybutyrate) depending on substrate availability, hormonal status and cardiac demands. These substrates differ with regard to myocardial energy efficiency (MEE) (cardiac work related to oxygen consumption). Since high MEE is associated with a better prognosis in HFrEF, manipulating substrate uptake could be a new treatment modality in heart failure patients.

Recently, it was shown that the human myocardium increases 3-hydroxybutyrate (3-OHB) metabolism during development of HFrEF. These changes may be beneficial as 3-OHB could increase myocardial efficiency and lower oxidative stress by scavenging free radicals. However, until now this has not been investigated in clinical trials, and the effect of 3-OHB on cardiac function, oxygen consumption and perfusion remains undetermined in HFrEF patients.

In the present study the investigators will evaluate whether elevated circulating 3-OHB affect myocardial oxygen consumption, MEE and perfusion in healthy subjects and patients with HFrEF, and whether 3-OHB affect hemodynamics and contractile function.

10 healthy test subjects and 20 HFrEF patients will be subjected to placebo and 3-OHB infusion in a randomized cross-over design. Acetate-PET, echocardiography and right sided heart catheterization will be applied.

Conditions

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Heart Failure, Systolic Ketonemia

Keywords

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Myocardial metabolism Positron emission tomography Echocardiography Right sided heart catheterization

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Randomized dobbel-blinded crossover
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Control - Healthy test subjects

Age matched subjects without symptoms of heart failure or ischemic heart disease N=10

Group Type EXPERIMENTAL

Infusion of 3-OHB

Intervention Type BIOLOGICAL

Increase in 3-OHB levels

Infusion of placebo

Intervention Type BIOLOGICAL

NaCl

HFrEF - Heart failure patients investigated by PET

Patients with heart failure (HFrEF) N=12

Group Type EXPERIMENTAL

Infusion of 3-OHB

Intervention Type BIOLOGICAL

Increase in 3-OHB levels

Infusion of placebo

Intervention Type BIOLOGICAL

NaCl

HFrEF - Right heart catheterization

Patients with heart failure (HFrEF) N=12

Group Type EXPERIMENTAL

Infusion of 3-OHB

Intervention Type BIOLOGICAL

Increase in 3-OHB levels

Infusion of placebo

Intervention Type BIOLOGICAL

NaCl

HFrEF - Right heart catheterization study 2

Dose finding study (increasing dosage of 3-OHB)

Group Type EXPERIMENTAL

Infusion of 3-OHB

Intervention Type BIOLOGICAL

Increase in 3-OHB levels

Infusion of placebo

Intervention Type BIOLOGICAL

NaCl

Interventions

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Infusion of 3-OHB

Increase in 3-OHB levels

Intervention Type BIOLOGICAL

Infusion of placebo

NaCl

Intervention Type BIOLOGICAL

Other Intervention Names

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Na-3-OHB NaCl

Eligibility Criteria

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Inclusion Criteria

* For participants with heart failure:
* Symptoms of Heart failure NYHA 2-3
* LVEF\<40%

For all participants:

* Negative HCG for women in the pregnant age

Exclusion Criteria

* Significant cardiac valve disease
* Signs or history of major myocardial infarction (STEMI) within 3 months
* Other disease or treatment making subject unsuitable for study participation
* Treatment for diabetes or HbA1c level \>7%
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Aarhus

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Roni R Nielsen, MD PHD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Cardiology

Locations

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Dept. of cardiology, Aarhus university hospital Skejby

Aarhus, Central Jutland, Denmark

Site Status

Countries

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Denmark

Other Identifiers

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1-10-72-316-16

Identifier Type: -

Identifier Source: org_study_id