Hemodynamic Effects of Chronic Ketosis.

Study Overview
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Brief Summary
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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%. 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 are 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. 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 in patients with HF and reduced left ventricular ejection fraction (HFrEF). Presently there are no data on the clinical cardiovascular effects of long-term oral ketone-supplementation in patients with chronic HF. In this study we aim to investigate the effect of 14 days modulation of circulating ketone body levels on cardiac function and exercise capacity in patients with HFrEF.

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

Conditions
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Heart Failure

Intervention / Treatment
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* Dietary Supplement: Ketone monoester (3-OHB)
* Dietary Supplement: Placebo drink


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic heart failure with NYHA II-III Left ventricular ejection fraction ≤40% Negative urine-HCG for women with childbearing potential Exclusion Criteria: Known diabetes or HbA1c ≥48 mmol/mol Significant cardiac valve disease Severe stable angina pectoris Age <18 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketone monoester (3-OHB)<br> | Dietary Supplement: Ketone monoester (3-OHB)<br>* Commercially available ketone supplement<br>|
| Experimental: Isocaloric placebo<br> | Dietary Supplement: Placebo drink<br>* Isocaloric placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting cardiac output (L/min) | Measured with right heart catheterization | 14 days of dietary supplement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting pulmonary capillary wedge pressure (PCWP) | Measured with right heart catheterization | 14 days of dietary supplement | 
| Peak exercise pulmonary capillary wedge pressure (PCWP) | Measured with right heart catheterization | 14 days of dietary supplement | 
| Peak exercise cardiac output (L/min) | Measured with right heart catheterization | 14 days of dietary supplement | 
| Exercise capacity (METs) | Cardiopulmonary exercise test | 14 days of dietary supplement |