The Effect of Sustainable Diet Combined with Time-Restricted Eating and Probiotic Supplementation on Cardiovascular Function among Patients with Chronic Heart Failure with reduced Ejection Fraction (HFrEF): A Randomized Clinical Trial Study

Preparation of LP299v Probiotic Supplements Investigating of a sustainable diet in combination with TRE and probiotic supplements on cardiovascular function among patients with HFrEF

A controlled clinical trial, parallel-group, single-blind, randomized, phase 3, among 90 HFrEF patients

This study is conducted in two phases, the probiotic capsule preparation phase and the clinical phase. The place of the study will be the cohort center of MUMS. After confirming the diagnosis of HFrEF by cardiologists, participants will be referred to the specialist for more detailed explanations if they participate in the project. After controlling inclusion criteria, the participants are assigned to one of the 3 study groups using stratified blocked randomization method and researcher and participants will be blinded. Also, unique codes generating by online website will be assigned on the medicinal container. As each person enters to study regarding to randomized consequences, medicinal container is assigned to person and no one (researcher and participants) know which participants will be in which intervention group. Medicine containers will also be opaque with closed lids and capsules will be the same in appearance, color, taste and smell.

Inclusion criteria: Clinical diagnosis of HFrEF Men and women with age range of 30-75 years, Complete the informed consent form Exclusion criteria: Using nutritional supplements, Not consuming more than 20% of the capsules, Unwillingness to continue cooperation in research

Participants will be randomly divided into 3 groups: Dietary Advices + Probiotic Placebo: A Sustainable Diet with Time Restricted Eating + Probiotic Placebo: B Sustainable Diet with Time Restricted Eating + Probiotic Capsule: C

Echocardiography, biochemical and anthropometric indices

We kindly request an update to the trial record due to modifications in the title and certain aspects of the methods used.

In this study, we will use stratified blocked randomization for random allocation. Body mass index (BMI) is considered as a classifier variable. By using the site www.sealdenvelope.com and the classifier variable (BMI) and selecting blocks of 6 on the site, a random sequence will be generated. The mentioned sequences are placed in opaque, numbered and sealed envelopes or SNOSE by the research associate. Upon entering each patient, after obtaining informed consent and checking the inclusion and non-inclusion and exclusion criteria, the first envelope is opened and the patient is assigned to one of the 3 relevant groups. In the same way, the randomization process will continue until the last patient. In order to apply concealment allocation in the random allocation process, unique codes will be used on medicine containers. So that the desired code is also generated by the online website. As each person enters the study based on the generated sequence, the medicine container in which the desired code is recorded is assigned to the person and therefore, before choosing the person, no one is aware of the type of treatment he/ she will receive. Medicine containers are also non-transparent closed lids and capsules will be the same in terms of quantity, color, taste and smell.

This study is not blinded in terms of diet but will be blinded in terms of supplements. The probiotic supplement and its placebo will be produced by PARSILACT Company. All probiotic and its placebo supplements will provided by PARSILACT Company in prepacked pharmaceutical polyethylene bottle numbered for each patient according to the randomization sequence. The probiotic supplement and its placebo will be in the same form package. The researcher and patients will not be aware of the pharmaceutical polyethylene bottle's content until the end of the trial.