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

Heart Failure With Reduced Ejection Fraction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04921293
• Other study ID #: UIE-3652-21-22-1
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2023
• Est. completion date: December 1, 2024

Study information

• Verified date: April 2022
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: Adrian Soto, Ph.D, MD.
• Phone: 5572191248
• Email: adrian.sotom[@]incmnsz.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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:

1. - A ketogenic diet (<50 gr of carbohydrates per day) incorporating current recommendations for heart failure (low sodium and liquids) for 10 days.

2. - Standard diet incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with exogenous ketones (ketone monoester) for 10 days.

3. - 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: December 1, 2024
• Est. primary completion date: October 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction
• Ketosis

Intervention

Behavioral:
• Ketogenic diet
A diet with <50gr of carbohydrates per day. Monosaturated fats consumption will encourage over saturated fats

Dietary Supplement:
• Exogenous ketones
Administration of ketone monoester 25 ml t.i.d

Behavioral:
• Standard diet + placebo
A standard diet incorporating current recommendations (low in sodium and low in liquids) for heart failure patients.

Locations

Country	Name	City	State
Mexico	INCMNSZ	Mexico City	Cdmx

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	University of Oxford

Country where clinical trial is conducted

Mexico, 

References & Publications (8)

Astrup A, Magkos F, Bier DM, Brenna JT, de Oliveira Otto MC, Hill JO, King JC, Mente A, Ordovas JM, Volek JS, Yusuf S, Krauss RM. Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Aug 18;76(7):844-857. doi: 10.1016/j.jacc.2020.05.077. Epub 2020 Jun 17. Review. — View Citation

Athinarayanan SJ, Adams RN, Hallberg SJ, McKenzie AL, Bhanpuri NH, Campbell WW, Volek JS, Phinney SD, McCarter JP. Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial. Front Endocrinol (Lausanne). 2019 Jun 5;10:348. doi: 10.3389/fendo.2019.00348. eCollection 2019. — View Citation

Aubert G, Martin OJ, Horton JL, Lai L, Vega RB, Leone TC, Koves T, Gardell SJ, Krüger M, Hoppel CL, Lewandowski ED, Crawford PA, Muoio DM, Kelly DP. The Failing Heart Relies on Ketone Bodies as a Fuel. Circulation. 2016 Feb 23;133(8):698-705. doi: 10.1161/CIRCULATIONAHA.115.017355. Epub 2016 Jan 27. Erratum in: Circulation. 2018 Oct 9;138(15):e422. — View Citation

Bertero E, Maack C. Metabolic remodelling in heart failure. Nat Rev Cardiol. 2018 Aug;15(8):457-470. doi: 10.1038/s41569-018-0044-6. Review. — View Citation

Nielsen R, Møller N, Gormsen LC, Tolbod LP, Hansson NH, Sorensen J, Harms HJ, Frøkiær J, Eiskjaer H, Jespersen NR, Mellemkjaer S, Lassen TR, Pryds K, Bøtker HE, Wiggers H. Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients. Circulation. 2019 Apr 30;139(18):2129-2141. doi: 10.1161/CIRCULATIONAHA.118.036459. — View Citation

Norwitz NG, Loh V. A Standard Lipid Panel Is Insufficient for the Care of a Patient on a High-Fat, Low-Carbohydrate Ketogenic Diet. Front Med (Lausanne). 2020 Apr 15;7:97. doi: 10.3389/fmed.2020.00097. eCollection 2020. — View Citation

Soto-Mota A, Norwitz NG, Clarke K. Why a d-ß-hydroxybutyrate monoester? Biochem Soc Trans. 2020 Feb 28;48(1):51-59. doi: 10.1042/BST20190240. Review. — View Citation

Soto-Mota A, Vansant H, Evans RD, Clarke K. Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. Regul Toxicol Pharmacol. 2019 Dec;109:104506. doi: 10.1016/j.yrtph.2019.104506. Epub 2019 Oct 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ejection fraction Improvement	Estimated by cardiac MRI	10 days
Secondary	Clinical severity	Estimated with the NYHA classification	10 days
Secondary	Liquid retention	Estimated by electric bioimpedance	10 days
Secondary	Blood biomarker	BNP	10 days