Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects (KETO-KINETICS1)
Primary Purpose
Heart Failure, Ketosis, Ketonemia
Status
Active
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Oral 3-hydroxybutyrate salts
Carbohydrate Placebo
Ketone Monoester
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Metabolism
Eligibility Criteria
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.
Sites / Locations
- Aarhus University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Single dose oral 3-hydroxybutyrate monoester
Single dose oral 3-hydroxybutyrate Salt
Single dose oral placebo
Arm Description
Cross-over study in 8 patients receiving single-dose oral 3-hydroxybutyrate monoester, 3-OHB salt and placebo.
maltodextrin-based, isocaloric to ketone dosis.
Outcomes
Primary Outcome Measures
Cardiac Output (L/min)
Right Heart Catherization
Secondary Outcome Measures
Left Ventricle Ejection Fraction (%)
Echocardiography
Left Ventricular filling pressure (mmHg)
Right Heart Catherization
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04443426
Brief Title
Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects
Acronym
KETO-KINETICS1
Official Title
Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 25, 2019 (Actual)
Primary Completion Date
November 1, 2022 (Anticipated)
Study Completion Date
November 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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:
If this effect is reproducible with a commercially available oral ketone supplements
The safety of commercially available ketone supplements in heart failure patients
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Ketosis, Ketonemia
Keywords
Metabolism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single dose oral 3-hydroxybutyrate monoester
Arm Type
Experimental
Arm Description
Cross-over study in 8 patients receiving single-dose oral 3-hydroxybutyrate monoester, 3-OHB salt and placebo.
Arm Title
Single dose oral 3-hydroxybutyrate Salt
Arm Type
Experimental
Arm Title
Single dose oral placebo
Arm Type
Placebo Comparator
Arm Description
maltodextrin-based, isocaloric to ketone dosis.
Intervention Type
Dietary Supplement
Intervention Name(s)
Oral 3-hydroxybutyrate salts
Intervention Description
Comercially available 3-hydroxybutyrate salts with 36 grams of 3-OHB salts three times daily.
Intervention Type
Dietary Supplement
Intervention Name(s)
Carbohydrate Placebo
Intervention Description
Comercially available carbohydrate sports drink. The placebo dose is isocaloric to the 3-hydroxy butyrate dose.
Intervention Type
Dietary Supplement
Intervention Name(s)
Ketone Monoester
Intervention Description
Commercially available ketone monoester in a dosage isocaloric to 3-OHB salts.
Primary Outcome Measure Information:
Title
Cardiac Output (L/min)
Description
Right Heart Catherization
Time Frame
5 hours - Area under the curve
Secondary Outcome Measure Information:
Title
Left Ventricle Ejection Fraction (%)
Description
Echocardiography
Time Frame
5 Hours - Area under the curve
Title
Left Ventricular filling pressure (mmHg)
Description
Right Heart Catherization
Time Frame
5 hours - Area under the curve
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristian H Christensen, MD
Organizational Affiliation
Aarhus Universitetshospital - Department of Cardiology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
12. IPD Sharing Statement
Learn more about this trial
Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects
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