Ketones in Heart Failure - Effects on Cardiac Efficiency

December 8, 2017 updated by: University of Aarhus

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Region Midtjylland
      • Aarhus, Region Midtjylland, Denmark, 8200
        • Dept. of cardiology, Aarhus university hospital Skejby

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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%

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Control - Healthy test subjects
Age matched subjects without symptoms of heart failure or ischemic heart disease N=10
Biological: Infusion of 3-OHB
Increase in 3-OHB levels
Other Names:
  • Na-3-OHB
Biological: Infusion of placebo
NaCl
Other Names:
  • NaCl
EXPERIMENTAL: HFrEF - Heart failure patients investigated by PET
Patients with heart failure (HFrEF) N=12
Biological: Infusion of 3-OHB
Increase in 3-OHB levels
Other Names:
  • Na-3-OHB
Biological: Infusion of placebo
NaCl
Other Names:
  • NaCl
EXPERIMENTAL: HFrEF - Right heart catheterization
Patients with heart failure (HFrEF) N=12
Biological: Infusion of 3-OHB
Increase in 3-OHB levels
Other Names:
  • Na-3-OHB
Biological: Infusion of placebo
NaCl
Other Names:
  • NaCl
EXPERIMENTAL: HFrEF - Right heart catheterization study 2
Dose finding study (increasing dosage of 3-OHB)
Biological: Infusion of 3-OHB
Increase in 3-OHB levels
Other Names:
  • Na-3-OHB
Biological: Infusion of placebo
NaCl
Other Names:
  • NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial efficiency
Time Frame: 1 day
Based on myocardial PET examinations
1 day
Cardiac output
Time Frame: 1 day
Right sided heart catheterization
1 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial perfusion
Time Frame: 1 day
Based on myocardial PET examinations
1 day
Myocardial oxygen consumption
Time Frame: 1 day
Based on myocardial PET examinations
1 day
Pulmonary and wedge pressure
Time Frame: 1 day
Right sided heart catheterization
1 day
Mixed venous saturation
Time Frame: 1 day
Right sided heart catheterization
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Investigators

  • Principal Investigator: Roni R Nielsen, MD PHD, Dept. of Cardiology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 17, 2017

Primary Completion (ACTUAL)

November 16, 2017

Study Completion (ACTUAL)

November 16, 2017

Study Registration Dates

First Submitted

February 20, 2017

First Submitted That Met QC Criteria

March 2, 2017

First Posted (ACTUAL)

March 8, 2017

Study Record Updates

Last Update Posted (ACTUAL)

December 11, 2017

Last Update Submitted That Met QC Criteria

December 8, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1-10-72-316-16

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Heart Failure, Systolic

Clinical Trials on Infusion of 3-OHB

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Panama

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe