Effects of 2-week Ketosis on the Heart's Ketone Body Consumption, Utilization, and Energetic Efficiency in Patients With Chronic Heart Failure (KETO-CHF PET)

August 27, 2025 updated by: Henrik Wiggers, Aarhus University Hospital

Effects of 2-week Ketosis on Myocardial Ketone Body Consumption, Utilization, and External Efficiency in Patients With Chronic Heart Failure

Heart Failure (HF) is a significant health concern, affecting around 1-2% of people in Western countries. The risk of developing HF during a lifetime is about 20%. Despite advancements in HF care, the one-year mortality rate for HF patients remains high. HF patients also experience reduced physical capacity and quality of life. The heart relies heavily on a process called oxidative metabolism for energy, and this process requires a continuous supply of energy sources like fatty acids, glucose, and ketone bodies. In HF, there's a shift in how the heart uses these energy sources, which affects its efficiency.

Ketone bodies such as 3-OHB, are molecules that can provide the heart with a more efficient energy source compared to traditional ones like fatty acids or glucose. They are produced in the liver and are important for supplying energy during fasting, exercise, and illness. Recent research suggests that 3-OHB might have benefits for HF patients beyond just providing energy. It seems to reduce inflammation and oxidative stress in the heart. Some studies in healthy individuals have shown that infusing 3-OHB increases blood flow to the heart.

In HF patients, the investigators aim to explore the cardiac effects of a two-week supplement of 3-OHB. The aim is to investigate if this supplement can increase the heart's consumption and utilization of 3-OHB. The study involves 12 patients with HF and reduced ejection fraction (HFrEF). The patients will receive a ketone ester supplement four times a day for two weeks, and then they'll take an isocaloric placebo supplement for another two weeks.

The investigators will use positron emission tomography (PET) to study the cardiac oxygen consumption and 3-OHB uptake. This is done by injection of tracers (11-C-3-OHB and 11-C-acetate).

The study will also look at myocardial external efficiency (MEE) and myocardial blood flow (MBF). For a subset of participants, the investigators will also take myocardial biopsies and perform more detailed analyses, e.g. respirometry and electron microscopy or single nucleus mRNA sequencing, proteomics and metabolimcs, to understand the impact of the supplement on the heart's cellular structures and functions, transcriptome, proteome and metabolome.

Ultimately, this study aims to determine whether supplementing HF patients with 3-OHB can improve the heart's energy usage and potentially provide other beneficial effects. This research might pave the way for new treatments that enhance the heart's function and quality of life for HF patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Not Applicable

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
    • Central Jutland
      • Aarhus, Central Jutland, Denmark, 8200
        • Aarhus University Hospital

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diabetes or HbA1c > 48 mmol/L
  • significant cardiac valve disease
  • severe stable angina pectoris
  • severe comorbidity as judged by the investigator
  • inability to give informed consent
  • Age <55 years
  • Other disease or treatment making subject unsuitable for study participation as judged by the investigator

Exclusion Criteria:

  • Chronic heart failure
  • NYHA class II-III
  • left ventricular ejection fraction (LVEF) <40%
  • Negative urine-HCG for women with childbearing potential

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 3-hydroxybutyrate
Dietary supplement: 3-hydroxybutyrat
The intervention is administered as a drink.
Placebo Comparator: Isocaloric placebo drink
Dietary supplement: Isocaloric placebo drink
The intervention is administered as a drink.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial consumption of 3-OHB.
Time Frame: Participants meet for 2 examination days 4 weeks apart. This is a whole day involving 4 PET/CT scans each day.
Uptake of the ketone radiotracer measured in µmol/min/g tissue in the myocardium will be calculated using kinetic modeling techniques using aQuant Research software.
Participants meet for 2 examination days 4 weeks apart. This is a whole day involving 4 PET/CT scans each day.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial oxygen consumption (MVO2)
Time Frame: Participants meet for 2 examination days 4 weeks apart. This is a whole day involving 4 PET/CT scans each day.
Uptake and oxidation of the acetate radiotracer measured in mL/g/min tissue in the myocardium will be calculated using kinetic modeling techniques using aQuant Research software
Participants meet for 2 examination days 4 weeks apart. This is a whole day involving 4 PET/CT scans each day.
Myocardial external efficacy
Time Frame: Participants meet for 2 examination days 4 weeks apart. This is a whole day involving 4 PET/CT scans each day.
Refers to a measure that assesses how effectively the heart converts its energy consumption into external work. It's a parameter that evaluates the efficiency of the heart's mechanical function in relation to its energy utilization.
Participants meet for 2 examination days 4 weeks apart. This is a whole day involving 4 PET/CT scans each day.
High resolution respirometry
Time Frame: Participants meet for 2 examination days 4 weeks apart. For a subset of participants, 1 myocardial biopsy and 2 skeletal muscle biopsies will be taken at each examination day.
Picomolar/second/mg tissue. This unit quantifies the rate at which oxygen is consumed by the biological sample being studied.
Participants meet for 2 examination days 4 weeks apart. For a subset of participants, 1 myocardial biopsy and 2 skeletal muscle biopsies will be taken at each examination day.
Single nucleus mRNA sequencing of skeletal muscle and cardiomyocytes.
Time Frame: Participants meet for 2 examination days 4 weeks apart. For a subset of participants, 1 myocardial biopsy and 2 skeletal muscle biopsies will be taken at each examination day.
Sequencing of mRNA (the transcriptome) from the nucleus of a single skeletal muscle cell and cardiomyocyte.
Participants meet for 2 examination days 4 weeks apart. For a subset of participants, 1 myocardial biopsy and 2 skeletal muscle biopsies will be taken at each examination day.
Proteomics of skeletal muscle and myocardial biopsies.
Time Frame: Participants meet for 2 examination days 4 weeks apart. For a subset of participants, 1 myocardial biopsy and 2 skeletal muscle biopsies will be taken at each examination day.
Systematic analysis of the entire complement of proteins (the proteome) present in the skeletal muscle and myocardial biopsies. This includes identifying proteins, determining their abundance, studying their post-translational modifications.
Participants meet for 2 examination days 4 weeks apart. For a subset of participants, 1 myocardial biopsy and 2 skeletal muscle biopsies will be taken at each examination day.
Metabolomics of skeletal muscle and myocardial biopsies.
Time Frame: Participants meet for 2 examination days 4 weeks apart. For a subset of participants, 1 myocardial biopsy and 2 skeletal muscle biopsies will be taken at each examination day.
Characterizing the entire complement of metabolites (the metabolome) in the skeletal muscle and myocardial biopsies.
Participants meet for 2 examination days 4 weeks apart. For a subset of participants, 1 myocardial biopsy and 2 skeletal muscle biopsies will be taken at each examination day.

Collaborators and Investigators

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

Sponsor

Aarhus University Hospital

Investigators

  • Principal Investigator: Henrik Henrik, Professor, Aarhus University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

November 21, 2023

Primary Completion (Actual)

April 8, 2025

Study Completion (Actual)

April 8, 2025

Study Registration Dates

First Submitted

August 23, 2023

First Submitted That Met QC Criteria

May 1, 2024

First Posted (Actual)

May 3, 2024

Study Record Updates

Last Update Posted (Estimated)

September 4, 2025

Last Update Submitted That Met QC Criteria

August 27, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KETO-CHF-PET

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

product manufactured in and exported from the U.S.

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.

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