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

NCT ID: NCT04921293

Last Updated: 2022-10-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-01

Study Completion Date

2024-12-01

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:

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.

Conditions

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Heart Failure With Reduced Ejection Fraction Ketosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized controlled trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard Diet

Standard diet incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with bitter taste placebo.

Group Type ACTIVE_COMPARATOR

Standard diet + placebo

Intervention Type BEHAVIORAL

A standard diet incorporating current recommendations (low in sodium and low in liquids) for heart failure patients.

Endogenous Ketosis

Ketogenic diet incorporating current recommendations for heart failure (\<50gr of carbohydrates, low sodium, and liquids) for 10 days.

Group Type EXPERIMENTAL

Ketogenic diet

Intervention Type BEHAVIORAL

A diet with \<50gr of carbohydrates per day. Monosaturated fats consumption will encourage over saturated fats

Exogenous ketosis

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

Group Type EXPERIMENTAL

Exogenous ketones

Intervention Type DIETARY_SUPPLEMENT

Administration of ketone monoester 25 ml t.i.d

Interventions

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Ketogenic diet

A diet with \<50gr of carbohydrates per day. Monosaturated fats consumption will encourage over saturated fats

Intervention Type BEHAVIORAL

Exogenous ketones

Administration of ketone monoester 25 ml t.i.d

Intervention Type DIETARY_SUPPLEMENT

Standard diet + placebo

A standard diet incorporating current recommendations (low in sodium and low in liquids) for heart failure patients.

Intervention Type BEHAVIORAL

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Oxford

OTHER

Sponsor Role collaborator

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adrian Soto, Ph.D, MD.

Role: PRINCIPAL_INVESTIGATOR

INCMNSZ

Locations

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INCMNSZ

Mexico City, Mexico City, Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Adrian Soto, Ph.D, MD.

Role: CONTACT

5572191248

Jorge Oseguera, MD

Role: CONTACT

54870900 ext. 8210

Facility Contacts

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Adrian Soto, Ph.D, MD.

Role: primary

5572191248

References

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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.

Reference Type BACKGROUND
PMID: 32562735 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31231311 (View on PubMed)

Aubert G, Martin OJ, Horton JL, Lai L, Vega RB, Leone TC, Koves T, Gardell SJ, Kruger 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.

Reference Type BACKGROUND
PMID: 26819376 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29915254 (View on PubMed)

Nielsen R, Moller N, Gormsen LC, Tolbod LP, Hansson NH, Sorensen J, Harms HJ, Frokiaer J, Eiskjaer H, Jespersen NR, Mellemkjaer S, Lassen TR, Pryds K, Botker 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.

Reference Type BACKGROUND
PMID: 30884964 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32351962 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31655093 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 32096539 (View on PubMed)

Other Identifiers

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UIE-3652-21-22-1

Identifier Type: -

Identifier Source: org_study_id

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