High Fat Diet for Cardiac Metabolic Reprogramming

NCT06747429 | Not Yet Recruiting

• 2 other identifiers: CARDINNOV101095426
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

The heart is a unique organ that performs an incessant work to pump blood throughout the body. For this massive effort, it requires a very high supply of energy. Mitochondria are small components of the cells responsible for the production of energy. To produce energy, mitochondria from cardiac cells can use fuel of different origins (fats, glucose, proteins, etc). In normal circumstances, cardiac mitochondria use preferentially fats since they are more efficient in terms of quantify of energy produced. Recent data from our consortium has demonstrated that if the cardiac mitochondria switch the primary source of fuel (from fats to glucose), this results in a poor performance of the organ, which cannot supply the whole body with enough blood. This is known as heart failure. In experimental models of heart failure, we have demonstrated that a high fat diet is able to reverse the metabolic switch and make the cardiac cells mitochondria use again fats as the primary substrate to produce energy. This translates into a recovery of heart failure. In the present project, we plan to bring this concept to the human setting and perform a pilot clinical study where patients with heart failure are put in a dietary program consisting of high fat diet. The effect of this nutritional approach will be evaluated by state-of-the-art non-invasive imaging technology.

Conditions

Hearth Failure Secondary to Non-ischemic DCM with Reduced LVEF (≤40%)

Keywords

heart failure; dilated cardiomyopathy; high-fat diet; clinical trial

Outcome Measures

Primary Outcomes (1)

• Changes in left ventricular ejection fraction (LVEF)

  Changes in LVEF assessed using cardiac magnetic resonance imaging (MRI)

  At baseline, month 2 and month 4

Secondary Outcomes (17)

• Left ventricular strain

  At baseline, month 2 and month 4

• Diastolic function

  At baseline, month 2 and month 4

• White blood cells

  At baseline, month 2 and month 4

• Red blood cells

  At baseline, month 2 and month 4

• Hemoglobin

  At baseline, month 2 and month 4

Study Arms (2)

High fat diet

EXPERIMENTAL

Patients receiving a high-fat diet

Other: High fat diet

Control

ACTIVE COMPARATOR

Patients receiving a standard diet

Other: Standard diet

Interventions

High fat diet OTHER

Weekly isocaloric dietary profile, with total daily energy intake distributed as follows: 70% from fats, primarily sourced from nuts, extra virgin olive oil, avocados, and animal fats from fish and cheese; protein intake of 0.8-1.2 g per kg body weight (10-20%); and the remaining calories from carbohydrates (10-20%).

High fat diet

Standard diet OTHER

Weekly isocaloric dietary profile, with total daily energy intake distributed as follows: 30% from fats, primarily sourced from nuts, extra virgin olive oil, avocados, and animal fats from fish and cheese; protein intake of 0.8-1.2 g per kg body weight (10-20%); and 50-60% from carbohydrates.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis with HF secondary to non-ischemic DCM with reduced LVEF (≤40%)
• years or older
• informed consent provided

You may not qualify if:

• diagnosis of ischemic dilated cardiomyopathy
• recent changes in drug treatment
• significant HF impairment within the past year
• uncontrolled dyslipidemia
• claustrophobia
• presence of a pacemaker or implantable cardiac defibrillator (ICD)
• liver diseases
• life expectancy less than 12 months
• baseline fat intake exceeding 40% of total daily energy intake

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Careggi: lead
• INSTITUTO DE SALUD CARLOS III (ISCIII): collaborator
• Puerta de Hierro Majadahonda University Hospital: collaborator
• Nicole Karam, European Hospital Georges Pompidou, Paris, France: collaborator
• Carol Davila University of Medicine and Pharmacy Bucharest: collaborator

Related Publications (13)

• Watson WD, Green PG, Lewis AJM, Arvidsson P, De Maria GL, Arheden H, Heiberg E, Clarke WT, Rodgers CT, Valkovic L, Neubauer S, Herring N, Rider OJ. Retained Metabolic Flexibility of the Failing Human Heart. Circulation. 2023 Jul 11;148(2):109-123. doi: 10.1161/CIRCULATIONAHA.122.062166. Epub 2023 May 18.

  PMID: 37199155 BACKGROUND

• Stanley WC, Dabkowski ER, Ribeiro RF Jr, O'Connell KA. Dietary fat and heart failure: moving from lipotoxicity to lipoprotection. Circ Res. 2012 Mar 2;110(5):764-76. doi: 10.1161/CIRCRESAHA.111.253104.

  PMID: 22383711 BACKGROUND

• Stanley WC, Recchia FA. Lipotoxicity and the development of heart failure: moving from mouse to man. Cell Metab. 2010 Dec 1;12(6):555-6. doi: 10.1016/j.cmet.2010.11.016.

  PMID: 21109186 BACKGROUND

• Martinez-Milla J, Galan-Arriola C, Carnero M, Cobiella J, Perez-Camargo D, Bautista-Hernandez V, Rigol M, Solanes N, Villena-Gutierrez R, Lobo M, Mateo J, Vilchez-Tschischke JP, Salinas B, Cusso L, Lopez GJ, Fuster V, Desco M, Sanchez-Gonzalez J, Ibanez B. Translational large animal model of hibernating myocardium: characterization by serial multimodal imaging. Basic Res Cardiol. 2020 Apr 14;115(3):33. doi: 10.1007/s00395-020-0788-0.

  PMID: 32291522 BACKGROUND

• Wai T, Garcia-Prieto J, Baker MJ, Merkwirth C, Benit P, Rustin P, Ruperez FJ, Barbas C, Ibanez B, Langer T. Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. Science. 2015 Dec 4;350(6265):aad0116. doi: 10.1126/science.aad0116.

  PMID: 26785494 BACKGROUND

• Tan Y, Li M, Wu G, Lou J, Feng M, Xu J, Zhou J, Zhang P, Yang H, Dong L, Li J, Zhang X, Gao F. Short-term but not long-term high fat diet feeding protects against pressure overload-induced heart failure through activation of mitophagy. Life Sci. 2021 May 1;272:119242. doi: 10.1016/j.lfs.2021.119242. Epub 2021 Feb 16.

  PMID: 33607155 BACKGROUND

• Guo Y, Wang Z, Qin X, Xu J, Hou Z, Yang H, Mao X, Xing W, Li X, Zhang X, Gao F. Enhancing fatty acid utilization ameliorates mitochondrial fragmentation and cardiac dysfunction via rebalancing optic atrophy 1 processing in the failing heart. Cardiovasc Res. 2018 Jun 1;114(7):979-991. doi: 10.1093/cvr/cvy052.

  PMID: 29490017 BACKGROUND

• Duda MK, O'Shea KM, Lei B, Barrows BR, Azimzadeh AM, McElfresh TE, Hoit BD, Kop WJ, Stanley WC. Low-carbohydrate/high-fat diet attenuates pressure overload-induced ventricular remodeling and dysfunction. J Card Fail. 2008 May;14(4):327-35. doi: 10.1016/j.cardfail.2007.11.003.

  PMID: 18474346 BACKGROUND

• Fillmore N, Mori J, Lopaschuk GD. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br J Pharmacol. 2014 Apr;171(8):2080-90. doi: 10.1111/bph.12475.

  PMID: 24147975 BACKGROUND

• Neubauer S. The failing heart--an engine out of fuel. N Engl J Med. 2007 Mar 15;356(11):1140-51. doi: 10.1056/NEJMra063052. No abstract available.

  PMID: 17360992 BACKGROUND

• Doenst T, Nguyen TD, Abel ED. Cardiac metabolism in heart failure: implications beyond ATP production. Circ Res. 2013 Aug 30;113(6):709-24. doi: 10.1161/CIRCRESAHA.113.300376.

  PMID: 23989714 BACKGROUND

• McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.

  PMID: 34447992 BACKGROUND

• Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC, Coats AJS. Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res. 2023 Jan 18;118(17):3272-3287. doi: 10.1093/cvr/cvac013.

  PMID: 35150240 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Cardiomyopathy, Dilated

Interventions

Diet, High-Fat

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Cardiomegaly; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Central Study Contacts

Francesco Sofi, Phd, MD

CONTACT

+39 0557946519; francesco.sofi@unifi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Masking will be maintained for data analysts.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: December 24, 2024
• Study Start: March 1, 2025
• Primary Completion: December 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share