Probiotics and Systemic Inflammation in Patients With Metabolic Syndrome and High Cardiovascular Risk

NCT ID: NCT04232852

Last Updated: 2022-04-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-12
• Study Completion Date: 2021-01-26

Brief Summary

Metabolic Syndrome (MetS) and cardiovascular disease are associated with systemic inflammation (SI). Activation of the mechanisms of inflammation is triggered by the inflammatory cytokines. Τhe NLRP3 inflammasome is activated by microbial-derived low molecular weight (LMW) factors, short chain fatty acids (SCFAs), pathogen-associated molecular pattern molecules (PAMPs), damage-associated molecular pattern molecules (DAMPs), and monosodium urate crystals. Probiotics can regulate inflammation in two ways: 1) indirectly, by producing SCFAs as well as increasing synthesis of antimicrobial peptides and 2) directly, by binding innate immune system receptors Toll-like (TLR 2, 4, 9) and triggering important signaling pathways associated with activation of NLRs affecting the formation of inflammasome, thus the inflammatory response.

Detailed Description

Metabolic Syndrome (MetS) is associated with low-grade systemic inflammation (SI). Activation of the mechanisms of inflammation is triggered by the inflammatory cytokines produced in the adipose tissue. Among them, IL-1β interleukin plays a central role in cardiovascular disease. The active form of IL-1β results by the conversion of its inactive precursor after an infectious/inflammatory stimulus. The Nucleotide-binding Oligomerization Domain (NOD)-like Receptor containing Pyrin domain 3 (NLRP3 or cryopyrin) inflammasome is a multiprotein complex that activates caspase 1, leading to the processing and secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β) via the NLRP3/caspase pathway. Τhe NLRP3 inflammasome is activated by microbial-derived Low Molecular Weight (LMW) factors, short chain fatty acids (SCFAs), Pathogen-associated molecular pattern molecules (PAMPs), Damage-associated molecular pattern molecules (DAMPs), and monosodium urate crystals.

It is a randomized, double-blind clinical trial in patients with MetS and cardiovascular disease. Patients will be randomized into two groups: A. those who will receive probiotic supplements and B. placebo-treated patients. Both groups will follow the usual clinical practice as far as drugs and diet concerned.

Τhe primary objective of this study is to investigate the effect of administration of the probiotic mix on IL-1β production by stimulated peripheral blood mononuclear cells (PBMCs) in patients at high cardiovascular risk with MetS at the end of the intervention. Secondly, to investigate the effect of probiotics on endothelial glycocalyx thickness, on hrCRP and on HbA1c levels, on the components of the MetS, on the gut microbiota at the end and 4 weeks after the completion of the intervention.

Time frame 12 weeks.

Conditions

Metabolic Syndrome; Cardiovascular Risk Factor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Probiotics

Demographics, anthropometric measurements (weight, height, waist circumference, BMI) will be recorded, clinical data related to the patient's cardiovascular risk (MI with or without angioplasty, acute coronary syndrome with or without angioplasty). Systolic and diastolic pressure will be measured before and after the 12-week intervention.

This group will receive a probiotic mix, which will contain strains of Streptococcus thermophilus, Saccharomyces cerevisiae, Lactobacillus acidophilus, L. rhamnosus L. helveticus, L. gasseri, L. plantarum, Bifidobacterium bifidum, Enterococcus faecium at a daily dose of 7 × 1010 CFU in the form of a capsule. During the intervention, participants will follow their eating habits as well as the physical activity of their personal routine, with the advice not to consume fermented dairy products.

Group Type: ACTIVE_COMPARATOR

Probiotic mix

Intervention Type: DIETARY_SUPPLEMENT

The probiotic mix will contain strains of Streptococcus thermophilus, Saccharomyces cerevisiae, Lactobacillus acidophilus, L. rhamnosus L. helveticus, L. gasseri, L. plantarum, Bifidobacterium bifidum, Enterococcus faecium at a daily dose of 7 × 1010 CFU in the form of a capsule.

Placebo supplement

Demographics, anthropometric measurements (weight, height, waist circumference, BMI) will be recorded, clinical data related to the patient's cardiovascular risk (MI with or without angioplasty, acute coronary syndrome with or without angioplasty). Systolic and diastolic pressure will be measured before and after the 12-week intervention.

Patients of this group will receive an identical capsule of maltodextrin (placebo). During the intervention, participants will follow their eating habits as well as the physical activity of their personal routine, with the advice not to consume fermented dairy products.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Patients in the placebo group will receive an identical capsule of maltodextrin.

Interventions

Probiotic mix

The probiotic mix will contain strains of Streptococcus thermophilus, Saccharomyces cerevisiae, Lactobacillus acidophilus, L. rhamnosus L. helveticus, L. gasseri, L. plantarum, Bifidobacterium bifidum, Enterococcus faecium at a daily dose of 7 × 1010 CFU in the form of a capsule.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Patients in the placebo group will receive an identical capsule of maltodextrin.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Patients≥50 years old, with diagnosed MetS and history of Myocardial Infarction (MI), angioplasty, acute coronary syndrome with or without angioplasty, after written consent.
• MetS syndrome defined by fulfilling at least 3 of the 5 following criteria: (NCEP-ATP-III) and "at high cardiovascular risk" as aforementioned.

Exclusion Criteria

• Body Mass Index (BMI) ≥ 40 (morbid obesity - difficult to manage, comorbidities)
• Probiotic intake three months prior to intervention
• Antibiotic intake three months prior to intervention
• Presence of inflammatory disease
• Inability to comply with study procedures

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Attikon Hospital

OTHER

Sponsor Role: lead

Responsible Party

Arezina Kasti

Head of Clinical Nutrition Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Arezina Kasti

Role: PRINCIPAL_INVESTIGATOR

Attikon University General Hospital

Locations

Attikon University General Hospital

Athens, , Greece

Countries

Greece

Other Identifiers

ΕΒΔ427/12-06-2019

Identifier Type: -

Identifier Source: org_study_id