Comparison Between Endogenous and Exogenous Ketosis in Patients With Non-ischemic Chronic Heart Failure With Reduced Ejection Fraction

Study Overview
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Brief Summary
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This randomized controlled trial will evaluate the effect of a ketogenic diet and/or exogenous administration of ketone bodies vs conventional diet on the ejection fraction of patients with non-ischemic chronic heart failure, measuring MRI biomarkers.

Detailed Description
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Evidence in both animals and humans suggests ketosis could be beneficial for people living with chronic heart failure. To date, no study has compared endogenous vs exogenous ketosis in patients with chronic heart failure. We will randomize (with a 1:1:1 ratio) patients with a confirmed diagnosis of non-ischemic chronic heart failure to undergo one of the following: - A ketogenic diet (<50 gr of carbohydrates per day) incorporating current recommendations for heart failure (low sodium and liquids) for 10 days. - Standard diet incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with exogenous ketones (ketone monoester) for 10 days. - Standard diet incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with bitter taste placebo. The endpoints will be assessed using cardiac MRI and blood biomarkers.

Official Title
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Comparison Between Endogenous and Exogenous Ketosis in Patients With Non-ischemic Chronic Heart Failure With Reduced Ejection Fraction

Conditions
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Heart Failure With Reduced Ejection Fraction, Ketosis

Intervention / Treatment
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* Behavioral: Ketogenic diet
* Dietary Supplement: Exogenous ketones
* Behavioral: Standard diet + placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ejection fraction <40% minimum 1 month. No change in optimum treatment 1 month at least. Exclusion Criteria: Ischemic cardiopathy (Angio-tomography corroborated cut-point >50% obstruction, coronary angiography, or cardiac scintigraphy 6 months at least) or angina pectoris symptoms. Reynaud syndrome Metformin or SGLT-2 Inhibitors treatment, Low BMI, nutritional deficiencies. Creatinin clearance <30ml/min or renal replacement therapy MRI contraindications (prothesis, Unsupported pacemakers, claustrophobia, etc) Reynaud phenomenon history

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: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Diet<br>Standard diet incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with bitter taste placebo. | Behavioral: Standard diet + placebo<br>* A standard diet incorporating current recommendations (low in sodium and low in liquids) for heart failure patients.<br>|
| Experimental: Endogenous Ketosis<br>Ketogenic diet incorporating current recommendations for heart failure (<50gr of carbohydrates, low sodium, and liquids) for 10 days. | Behavioral: Ketogenic diet<br>* A diet with <50gr of carbohydrates per day. Monosaturated fats consumption will encourage over saturated fats<br>|
| Experimental: Exogenous ketosis<br>Standard incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with exogenous ketones (ketone monoester) for 10 days. | Dietary Supplement: Exogenous ketones<br>* Administration of ketone monoester 25 ml t.i.d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ejection fraction Improvement | Estimated by cardiac MRI | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical severity | Estimated with the NYHA classification | 10 days | 
| Liquid retention | Estimated by electric bioimpedance | 10 days | 
| Blood biomarker | BNP | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endogenous ketosis, Exogenous ketosis, Heart failure