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| Name | Class |
|---|---|
| University of Oxford | OTHER |
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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.
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:
The endpoints will be assessed using cardiac MRI and blood biomarkers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard Diet | Active Comparator | Standard diet incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with bitter taste placebo. |
|
| Endogenous Ketosis | Experimental | Ketogenic diet incorporating current recommendations for heart failure (<50gr of carbohydrates, low sodium, and liquids) for 10 days. |
|
| Exogenous ketosis | Experimental | Standard incorporating current recommendations for heart failure (low sodium and liquids) and supplementation with exogenous ketones (ketone monoester) for 10 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketogenic diet | Behavioral | A diet with <50gr of carbohydrates per day. Monosaturated fats consumption will encourage over saturated fats |
|
| Measure | Description | Time Frame |
|---|---|---|
| Ejection fraction Improvement | Estimated by cardiac MRI | 10 days |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical severity | Estimated with the NYHA classification | 10 days |
| Liquid retention | Estimated by electric bioimpedance | 10 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Adrian Soto, Ph.D, MD. | Contact | 5572191248 | adrian.sotom@incmnsz.mx | |
| Jorge Oseguera, MD | Contact | 54870900 | 8210 | jorge.osegueram@incmnsz.mx |
| Name | Affiliation | Role |
|---|---|---|
| Adrian Soto, Ph.D, MD. | INCMNSZ | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| INCMNSZ | Recruiting | Mexico City | Mexico City | 14080 | Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32562735 | Background | 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. | |
| 31231311 |
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Upon request to PI
One year after publication
Send email to adrian.sotom@incmnsz.mx
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Randomized controlled trial
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| Exogenous ketones | Dietary Supplement | Administration of ketone monoester 25 ml t.i.d |
|
| Standard diet + placebo | Behavioral | A standard diet incorporating current recommendations (low in sodium and low in liquids) for heart failure patients. |
|
| Blood biomarker | BNP | 10 days |
| 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. |
| 26819376 | Background | 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. |
| 29915254 | Background | 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. |
| 30884964 | Background | 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. |
| 32351962 | Background | 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. |
| 31655093 | Background | 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. |
| 32096539 | Background | 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. |
| 40043832 | Derived | Kodur 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. |
| ID | Term |
|---|---|
| D007662 | Ketosis |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D000138 | Acidosis |
| D000137 | Acid-Base Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D055423 | Diet, Ketogenic |
| ID | Term |
|---|---|
| D050528 | Diet, Carbohydrate-Restricted |
| D004035 | Diet Therapy |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D004032 | Diet |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
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