Ketones in Heart Failure - Effects on Cardiac Efficiency

Heart Failure, Systolic Clinical Trial

Official title:

Effects of Ketones on Cardiac Function and Oxygen Consumption in Heart Failure Patients With Reduced Ejection Fraction and Healthy Test Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03073356
• Other study ID #: 1-10-72-316-16
• Status: Completed
• Phase: Phase 2
• First received: February 20, 2017
• Last updated: December 8, 2017
• Start date: March 17, 2017
• Est. completion date: November 16, 2017

Study information

• Verified date: January 2017
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: November 16, 2017
• Est. primary completion date: November 16, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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%

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Systolic
• Ketonemia

Intervention

Biological:
• Infusion of 3-OHB
Increase in 3-OHB levels
• Infusion of placebo
NaCl

Locations

Country	Name	City	State
Denmark	Dept. of cardiology, Aarhus university hospital Skejby	Aarhus	Region Midtjylland

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial efficiency	Based on myocardial PET examinations	1 day
Primary	Cardiac output	Right sided heart catheterization	1 day
Secondary	Myocardial perfusion	Based on myocardial PET examinations	1 day
Secondary	Myocardial oxygen consumption	Based on myocardial PET examinations	1 day
Secondary	Pulmonary and wedge pressure	Right sided heart catheterization	1 day
Secondary	Mixed venous saturation	Right sided heart catheterization	1 day