Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects

Heart Failure Clinical Trial

— KETO-KINETICS1  

Official title:

Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04443426
• Other study ID #: KETO- CHF 1-10-72-362-18
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 25, 2019
• Est. completion date: November 1, 2022

Study information

• Verified date: August 2022
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The ketone body 3-hydroxybutyrate (3-OHB) is a naturally occurring energy substrate, and is associated with increased life span and improved health. We have previously shown that intravenous 3-OHB treatment increases myocardial blood flow > 70% in healthy humans and data from our group show that 3-OHB increases cardiac output by 40 % in patients with heart failure.

In this study the investigators aim to investigate:

1. If this effect is reproducible with a commercially available oral ketone supplements

2. The safety of commercially available ketone supplements in heart failure patients

Description:

Heart Failure (HF) is a major public health issue because the disease affects 1-2% of the Western population and the lifetime risk of HF is 20%. HF is responsible for 1-2% of all healthcare expenditures. Despite major improvements in the management and care of patients with HF, the 1-year mortality in patients with HF is 13 % and >50% of HF-patients is admitted during a 2.5 year period. Furthermore patients with HF have markedly decreased physical capacity and quality of life. Thus, there is a need for new treatment modalities in this group of patients.

Ketone bodies are produced in the liver and are of vital importance in the human body for energy generation in the heart and brain during fasting, exercise and severe illness. Ketosis can be safely obtained using dietary supplements and can increase exercise capacity in athletes. The most important ketone bodies are 3-hydroxybutyrate (3-OHB) and acetoacetate. Recently, it was demonstrated that patients with severe HF have increased myocardial utilization of the ketone body 3-hydroxybutyrate.

We have shown, using positron emission tomography, that ketone body infusion reduces myocardial glucose uptake and increases myocardial blood flow in healthy subjects. Data from another study conducted by our group show a 40% increase in cardiac output during infusion of 3-OHB.

Presently there are no data on the clinical cardiovascular and metabolic effects of long-term oral ketone-supplementation in patients with chronic HF.

In this study the investigators will whether ketosis obtained by oral ketone supplements affects hemodynamics and contractile function.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 8
• Est. completion date: November 1, 2022
• Est. primary completion date: November 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chronic Heart Failure;

• NYHA class II-III

• Left Ventricular Ejection Fraction <40%

Exclusion Criteria:

• Diabetes or HbA1c > 48 mmol/mol

• Significant cardiac valve disease,

• Severe stable angina pectoris

• Severe comorbidity as judged by investigator,

• Inability to give informed consent.

Related Conditions & MeSH terms

• Heart Failure
• Ketonemia
• Ketosis

Intervention

Dietary Supplement:
• Oral 3-hydroxybutyrate salts
Comercially available 3-hydroxybutyrate salts with 36 grams of 3-OHB salts three times daily.
• Carbohydrate Placebo
Comercially available carbohydrate sports drink. The placebo dose is isocaloric to the 3-hydroxy butyrate dose.
• Ketone Monoester
Commercially available ketone monoester in a dosage isocaloric to 3-OHB salts.

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac Output (L/min)	Right Heart Catherization	5 hours - Area under the curve
Secondary	Left Ventricle Ejection Fraction (%)	Echocardiography	5 Hours - Area under the curve
Secondary	Left Ventricular filling pressure (mmHg)	Right Heart Catherization	5 hours - Area under the curve