The effect of a sustainable diet and time-restricted eating and probiotic in heart failure with reduced ejection fraction patients: study protocol for a randomized, double-blind, and placebo-controlled trial

Heart failure is a complex clinical syndrome characterized by structural and/or functional abnormalities that impair cardiac output, leading to alterations in cardiac biomarkers, metabolic disturbances, and gut dysbiosis. Lifestyle interventions, particularly dietary strategies such as time-restricted eating (TRE) and healthy diets like the sustainable diet (SD), along with probiotic supplementation, have been proposed as key components in the management of heart failure. Thus, the present study aims to evaluate the effects of co-administration of SD and TRE, either alone or in combination with Lactobacillus plantarum 299v supplementation, compared to control group, on cardiovascular function in overweight or obese patients with heart failure with reduced ejection fraction. We will conduct a randomized, double-blind, placebo-controlled, three-arm clinical trial over 60 days. Participants will be randomly assigned in a 1:1:1 ratio to one of three groups for 60 days: (A) co-administration of SD and TRE with probiotic supplementation (n = 25); (B) co-administration of SD and TRE with placebo supplementation (n = 25); and (C) control group with placebo supplementation (n = 25), serving as the control group. The primary outcomes will be changes in N-terminal pro-B-type natriuretic peptide and left ventricular ejection fraction. Secondary outcomes will include changes in fasting blood glucose, lipid profile, liver and kidney function markers, anthropometric indices, arterial stiffness, electrocardiogram indices, echocardiographic indices, sleep quality, appetite, energy intake, quality of life, exercise tolerance, and Zonulin and Trimethylamine N-oxide as gut-related biomarkers. All outcomes of this study will be evaluated before and after the intervention. We hypothesize that the co-administration of SD and 10-hour TRE, either alone or in combination with probiotic supplementation, will result in weight loss and improvements in metabolic, hormonal, and echocardiographic markers in overweight and obese patients with heart failure with reduced ejection fraction compared to control individuals. The present trial received approval from the Medical Ethics Committee of Mashhad University of Medical Sciences, Mashhad, Iran (IR.MUMS.REC.1402.259; approved on December 16, 2023). Iranian Registry of Clinical Trials (IRCT), IRCT20231225060520N1. Registered 23 January 2024, https://irct.behdasht.gov.ir/trial/74743.