Heart Failure With Reduced Ejection FractionNCT04921293
Comparison Between Endogenous and Exogenous Ketosis in Patients With Non-ischemic Chronic Heart Failure With Reduced Ejection Fraction
A study testing Ketogenic diet and Exogenous ketones in people with Heart Failure With Reduced Ejection Fraction and Ketosis, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction, Ketosis
- What is being tested?
- Ketogenic diet and Exogenous ketones
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteMexico
- Study dates
- 1 Jun 2023to 1 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ejection fraction <40% minimum 1 month.
- No change in optimum treatment 1 month at least.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Mexico1 site, 1 recruiting
- Recruiting
INCMNSZ
Mexico City, Mexico City, 14080
Adrian Soto, Ph.D, MD., 5572191248, adrian.sotom@incmnsz.com
About this study
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.
Read the 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.
- Being tested
- Ketogenic diet, Exogenous ketones, Standard diet + placebo
- Keywords
- Endogenous ketosis, Exogenous ketosis, Heart failure
- Medical subject headings
- Ketosis, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketogenic dietBehavioural
A diet with <50gr of carbohydrates per day. Monosaturated fats consumption will encourage over saturated fats
Exogenous ketonesDietary supplement
Administration of ketone monoester 25 ml t.i.d
Standard diet + placeboBehavioural
A standard diet incorporating current recommendations (low in sodium and low in liquids) for heart failure patients.
| Study group | Role | What they receive |
|---|---|---|
| Standard Diet | Active comparator | Standard diet incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with bitter taste placebo. Receives: Behavioral: Standard diet + placebo |
| Endogenous Ketosis | Experimental | Ketogenic diet incorporating current recommendations for heart failure (<50gr of carbohydrates, low sodium, and liquids) for 10 days. Receives: Behavioral: Ketogenic diet |
| Exogenous ketosis | Experimental | Standard incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with exogenous ketones (ketone monoester) for 10 days. Receives: Dietary Supplement: Exogenous ketones |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ejection fraction Improvement
Estimated by cardiac MRI
Measured: 10 days
Secondary outcomes (3)
Clinical severity
Estimated with the NYHA classification
Measured: 10 days
Liquid retention
Estimated by electric bioimpedance
Measured: 10 days
Blood biomarker
BNP
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2021
- Study start1 Jun 2023 (estimated)
- Primary completion20 Oct 2024 (estimated)
- Study completion1 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trial
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford
- Responsible party
- Sponsor
- Investigators
- Adrian Soto, Ph.D, MD., Principal investigator, INCMNSZ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04921293
- Sponsor's protocol ID
- UIE-3652-21-22-1
- Status last verified
- Apr 2022
- First submitted
- 2 Jun 2021
- Last updated
- 18 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon request to PI
Publications
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.
PubMed 32562735Athinarayanan 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.
PubMed 31231311Aubert 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.
PubMed 26819376Bertero E, Maack C. Metabolic remodelling in heart failure. Nat Rev Cardiol. 2018 Aug;15(8):457-470. doi: 10.1038/s41569-018-0044-6.
PubMed 29915254Nielsen 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.
PubMed 30884964Norwitz 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.
PubMed 32351962Soto-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.
PubMed 31655093Soto-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.
PubMed 32096539Kodur N, Nguyen C, Tang WHW. Therapeutic Ketosis for Heart Failure: A State-of-the-Art Review. J Card Fail. 2025 Jul;31(7):1051-1061. doi: 10.1016/j.cardfail.2025.01.028. Epub 2025 Mar 3.
PubMed 40043832
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison Between Endogenous and Exogenous Ketosis in Patients With Non-ischemic Chronic Heart Failure With Reduced Ejection Fraction
- ClinicalTrials.gov ID
- NCT04921293
- Acronym / sponsor ID
- UIE-3652-21-22-1
- Keywords
- Endogenous ketosis, Exogenous ketosis, Heart failure
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranUniversity, hospital or other
- Collaborators
- University of Oxford
- Study start
- 1 Jun 2023 (estimated)
- Primary completion
- 20 Oct 2024 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 10 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Standard Diet | Active comparator | Behavioral: Standard diet + placeboStandard diet incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with bitter taste placebo. |
| Endogenous Ketosis | Experimental | Behavioral: Ketogenic dietKetogenic diet incorporating current recommendations for heart failure (<50gr of carbohydrates, low sodium, and liquids) for 10 days. |
| Exogenous ketosis | Experimental | Dietary Supplement: Exogenous ketonesStandard incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with exogenous ketones (ketone monoester) for 10 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Ejection fraction <40% minimum 1 month.
- No change in optimum treatment 1 month at least.
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketogenic dietA diet with <50gr of carbohydrates per day. Monosaturated fats consumption will encourage over saturated fats | Behavioural | Endogenous Ketosis |
| Exogenous ketonesAdministration of ketone monoester 25 ml t.i.d | Dietary supplement | Exogenous ketosis |
| Standard diet + placeboA standard diet incorporating current recommendations (low in sodium and low in liquids) for heart failure patients. | Behavioural | Standard Diet |
Primary outcome
Ejection fraction Improvement
Time frame: 10 days
Estimated by cardiac MRI
3 secondary outcomes
Clinical severity
Time frame: 10 days
Liquid retention
Time frame: 10 days
Blood biomarker
Time frame: 10 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2022.
- Background: PubMed 32562735Astrup 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.
- Background: PubMed 31231311Athinarayanan 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.
- Background: PubMed 26819376Aubert 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.
- Background: PubMed 29915254Bertero E, Maack C. Metabolic remodelling in heart failure. Nat Rev Cardiol. 2018 Aug;15(8):457-470. doi: 10.1038/s41569-018-0044-6.
- Background: PubMed 30884964Nielsen 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.
- Background: PubMed 32351962Norwitz 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.
- Background: PubMed 31655093Soto-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.
- Background: PubMed 32096539Soto-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.
- Derived from this study: PubMed 40043832Kodur N, Nguyen C, Tang WHW. Therapeutic Ketosis for Heart Failure: A State-of-the-Art Review. J Card Fail. 2025 Jul;31(7):1051-1061. doi: 10.1016/j.cardfail.2025.01.028. Epub 2025 Mar 3.
- Individual participant dataSharing planned: Yes. Upon request to PI
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adrian Soto, Ph.D, MD. principal investigator
INCMNSZ
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketogenic diet and Exogenous ketones in people with Heart Failure With Reduced Ejection Fraction and Ketosis, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adrian Soto, Ph.D, MD. (5572191248, adrian.sotom@incmnsz.mx), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ejection fraction Improvement (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04921293, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2022.