High Fat Diet for Cardiac Metabolic Reprogramming

NCT06747429 | Recruiting

• 2 other identifiers: CARDINNOV101095426
• Study Type: interventional
• Target: 80
• Locations: 4 countries
• Sites: 5

Brief Summary

Heart failure (HF) continues to be a leading cause of morbidity and mortality worldwide, despite advances in treatment. HF is often characterized by an altered metabolism in the heart, where glucose is favored over fatty acids as the primary energy substrate. This metabolic shift has been hypothesized to contribute to disease progression. Previous studies using animal models have demonstrated that restoring fatty acid metabolism through dietary intervention can reverse the adverse metabolic effects and improve heart function. A transgenic murine model with mitochondrial defects, for instance, exhibited improved cardiac function after an HFD intervention. These findings were reinforced by a translational pig model of non-ischemic DCM, where a high-fat diet significantly improved LVEF compared to a standard diet. Building upon these promising preclinical results, a small-scale human study showed that lipid infusion, rather than glucose, improved cardiac function in HF patients. However, the long-term benefits of a HFD in heart failure patients have yet to be thoroughly explored. The HF4HF trial aims to fill this gap by evaluating the effects of an HFD over a two-month period in patients with non-ischemic DCM and reduced LVEF. The "High Fat Diet for Heart Failure" (HF4HF) study is a proof-of-concept randomized controlled trial designed to investigate the efficacy of a high-fat diet (HFD) as a therapeutic intervention in patients with non-ischemic dilated cardiomyopathy (DCM) and reduced left ventricular ejection fraction (LVEF). The study hypothesizes that cardiac metabolic reprogramming, achieved through a controlled nutritional intervention involving an HFD, can enhance systolic function, myocardial energetics, and overall heart function in heart failure (HF) patients. Cofunded by the European Commission and national entities, the trial is spearheaded by a consortium of cardiovascular research centers across four countries: Spain, Italy, France, and Romania.

Conditions

Non-ischemic Dilated Cardiomyopathy; Heart Failure With Reduced Ejection Fraction

Keywords

heart failure; high-fat diet; clinical trial; non-ischemic DCM

Outcome Measures

Primary Outcomes (1)

• Changes in left ventricular ejection fraction (LVEF)

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

  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:

• Patients of both sexes and ≥18 years old
• Patients diagnosed with HF secondary to non-ischemic DCM, according to ESC guidelines definition,1 with or without a known genetic basis.
• LVEF ≤49% according to the baseline CMR.
• Patients who have provided informed consent.

You may not qualify if:

• Prior diagnosis of ischemic DCM.
• Prior diagnosis of established atherosclerotic cardiovascular disease (angina/myocardial infarction, transient ischemic attack/stroke, lower limb ischemia or at any other peripheral level).
• Changes in HF therapies within the last 3 months.
• HF decompensation within the previous 3 months, including HF hospitalization or the need of ambulatory intravenous diuretic or inotropic treatment such as levosimendan.
• Uncontrolled dyslipidemia, defined as LDL-cholesterol \>160 mg/dL and/or triglycerides \>200 mg/dL, despite treatment.
• Any contraindication for CMR:
• Severe claustrophobia. Any device which is known to threaten or pose hazard in all MR environments. //www.mrisafety.com/ Patients with implanted biomedical devices (cardiac artefacts): pacemakers, cardiac defibrillators or cardiac resynchronization therapy.
• Liver and biliary diseases, including prior diagnosis of non-alcoholic fatty liver disease and unoperated cholelithiasis.
• Prior episodes of acute pancreatitis or chronic pancreatitis.
• Prior fish or nut allergy.
• Life expectancy less than 12 months.
• Pregnancy or planned pregnancy for the next 4 months.
• Current lactation.
• Patients participating in other randomized clinical trial.
• Impossibility to consent or undergo study follow-up

Sponsors & Collaborators

• Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III: lead
• Puerta de Hierro University Hospital: collaborator
• European Georges Pompidou Hospital: collaborator
• Carol Davila University of Medicine and Pharmacy: collaborator
• University of Florence: collaborator
• Hospital Universitario Fundación Jiménez Díaz: collaborator

Study Sites (5)

Hôpital Européen Georges Pompidou, INSERM

Paris, France

NOT YET RECRUITING

University of Florence, Clinical and Experimental Medicine, Unit of Clinical Nutrition,

Florence, Italy

NOT YET RECRUITING

University of Medicine and Pharmacy "Carol Davila", Bucharest,

Bucharest, Romania

RECRUITING

Fundación Investigación Biomédica Hospital Universitario Puerta de Hierro (IIS),

Madrid, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz,

Madrid, Spain

RECRUITING

Related Publications (7)

• 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. Corrigendum to: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2021 Dec 21;42(48):4901. doi: 10.1093/eurheartj/ehab670. No abstract available.

  PMID: 34649282 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

• Taegtmeyer H, Young ME, Lopaschuk GD, Abel ED, Brunengraber H, Darley-Usmar V, Des Rosiers C, Gerszten R, Glatz JF, Griffin JL, Gropler RJ, Holzhuetter HG, Kizer JR, Lewandowski ED, Malloy CR, Neubauer S, Peterson LR, Portman MA, Recchia FA, Van Eyk JE, Wang TJ; American Heart Association Council on Basic Cardiovascular Sciences. Assessing Cardiac Metabolism: A Scientific Statement From the American Heart Association. Circ Res. 2016 May 13;118(10):1659-701. doi: 10.1161/RES.0000000000000097. Epub 2016 Mar 24.

  PMID: 27012580 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

• 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

• 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

• Ibanez B, Aletras AH, Arai AE, Arheden H, Bax J, Berry C, Bucciarelli-Ducci C, Croisille P, Dall'Armellina E, Dharmakumar R, Eitel I, Fernandez-Jimenez R, Friedrich MG, Garcia-Dorado D, Hausenloy DJ, Kim RJ, Kozerke S, Kramer CM, Salerno M, Sanchez-Gonzalez J, Sanz J, Fuster V. Cardiac MRI Endpoints in Myocardial Infarction Experimental and Clinical Trials: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019 Jul 16;74(2):238-256. doi: 10.1016/j.jacc.2019.05.024.

  PMID: 31296297 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Heart Failure

Interventions

Diet, High-Fat

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Francesco Sofi, MD PhD

  University of Florence, Clinical and Experimental Medicine, Unit of Clinical Nutrition, Florence,

  PRINCIPAL INVESTIGATOR

• Pablo García Pavía,, MD PhD

  Fundación Investigación Biomédica Hospital Universitario Puerta de Hierro (IIS), Hospital Universitario Puerta de Hierro Majadahonda

  PRINCIPAL INVESTIGATOR

• Ruxandra Jurcut, MD PhD

  University of Medicine and Pharmacy "Carol Davila", Bucharest,

  PRINCIPAL INVESTIGATOR

• Jean-Sébastian Hulot, MD PhD

  Hôpital Européen Georges Pompidou, INSERM, Paris,

  PRINCIPAL INVESTIGATOR

• Mikel Taibo Urquía, MD

  Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

  PRINCIPAL INVESTIGATOR

• Borja Ibánez,, MD PhD

  Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

  STUDY CHAIR

Central Study Contacts

Carlos Nicolás Pérez-García, MD PhD.

CONTACT

(+34) 914531200; carlosnicolas.perez@cnic.es

Claudia Artiaga, MSc

CONTACT

(+34) 914531200; cartiaga@cnic.es

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

Model Details: The HF4HF trial is a proof-of-concept, independent investigator initiated (non commercial), multicentre, multinational, two-arm parallel randomized controlled trial, designed to evaluate the efficacy and safety of HFD compared to standard diet in patients with non-ischemic DCM and, at least, mildly reduced LVEF on optimal medical therapy. Despite participants and health care providers will not be blinded to the allocation arm, outcome assessors will; hence, it can be classified as a PROBE (prospective randomized open, blinded-endpoint) trial. As regards its duration, the trial will span 4 months in total: an intervention period of 2 months and an additional 2 months follow-up period to assess the sustained effects post-intervention discontinuation.

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: December 24, 2024
• Study Start: January 15, 2026
• Primary Completion: June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 26, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); RO (1); IT (1); FR (1)