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

Primary Purpose

Heart Failure With Reduced Ejection Fraction, Ketosis

Status
Recruiting
Phase
Not Applicable
Locations
Mexico
Study Type
Interventional
Intervention
Ketogenic diet
Exogenous ketones
Standard diet + placebo
Sponsored by
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction focused on measuring Endogenous ketosis, Exogenous ketosis, Heart failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • INCMNSZRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Standard Diet

Endogenous Ketosis

Exogenous ketosis

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Ejection fraction Improvement
Estimated by cardiac MRI

Secondary Outcome Measures

Clinical severity
Estimated with the NYHA classification
Liquid retention
Estimated by electric bioimpedance
Blood biomarker
BNP

Full Information

First Posted
June 2, 2021
Last Updated
October 17, 2022
Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Collaborators
University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT04921293
Brief Title
Comparison Between Endogenous and Exogenous Ketosis in Patients With Non-ischemic Chronic Heart Failure With Reduced Ejection Fraction
Official Title
Comparison Between Endogenous and Exogenous Ketosis in Patients With Non-ischemic Chronic Heart Failure With Reduced Ejection Fraction
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2023 (Anticipated)
Primary Completion Date
October 20, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Collaborators
University of Oxford

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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: - 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Reduced Ejection Fraction, Ketosis
Keywords
Endogenous ketosis, Exogenous ketosis, Heart failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomized controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard Diet
Arm Type
Active Comparator
Arm Description
Standard diet incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with bitter taste placebo.
Arm Title
Endogenous Ketosis
Arm Type
Experimental
Arm Description
Ketogenic diet incorporating current recommendations for heart failure (<50gr of carbohydrates, low sodium, and liquids) for 10 days.
Arm Title
Exogenous ketosis
Arm Type
Experimental
Arm Description
Standard incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with exogenous ketones (ketone monoester) for 10 days.
Intervention Type
Behavioral
Intervention Name(s)
Ketogenic diet
Intervention Description
A diet with <50gr of carbohydrates per day. Monosaturated fats consumption will encourage over saturated fats
Intervention Type
Dietary Supplement
Intervention Name(s)
Exogenous ketones
Intervention Description
Administration of ketone monoester 25 ml t.i.d
Intervention Type
Behavioral
Intervention Name(s)
Standard diet + placebo
Intervention Description
A standard diet incorporating current recommendations (low in sodium and low in liquids) for heart failure patients.
Primary Outcome Measure Information:
Title
Ejection fraction Improvement
Description
Estimated by cardiac MRI
Time Frame
10 days
Secondary Outcome Measure Information:
Title
Clinical severity
Description
Estimated with the NYHA classification
Time Frame
10 days
Title
Liquid retention
Description
Estimated by electric bioimpedance
Time Frame
10 days
Title
Blood biomarker
Description
BNP
Time Frame
10 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Adrian Soto, Ph.D, MD.
Phone
5572191248
Email
adrian.sotom@incmnsz.mx
First Name & Middle Initial & Last Name or Official Title & Degree
Jorge Oseguera, MD
Phone
54870900
Ext
8210
Email
jorge.osegueram@incmnsz.mx
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian Soto, Ph.D, MD.
Organizational Affiliation
INCMNSZ
Official's Role
Principal Investigator
Facility Information:
Facility Name
INCMNSZ
City
Mexico City
State/Province
Cdmx
ZIP/Postal Code
14080
Country
Mexico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adrian Soto, Ph.D, MD.
Phone
5572191248
Email
adrian.sotom@incmnsz.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Upon request to PI
IPD Sharing Time Frame
One year after publication
IPD Sharing Access Criteria
Send email to adrian.sotom@incmnsz.mx
Citations:
PubMed Identifier
32562735
Citation
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.
Results Reference
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PubMed Identifier
31231311
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.
Results Reference
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PubMed Identifier
26819376
Citation
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. Erratum In: Circulation. 2018 Oct 9;138(15):e422.
Results Reference
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PubMed Identifier
29915254
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.
Results Reference
background
PubMed Identifier
30884964
Citation
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.
Results Reference
background
PubMed Identifier
32351962
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.
Results Reference
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PubMed Identifier
31655093
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.
Results Reference
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PubMed Identifier
32096539
Citation
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.
Results Reference
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Comparison Between Endogenous and Exogenous Ketosis in Patients With Non-ischemic Chronic Heart Failure With Reduced Ejection Fraction

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