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

NCT04232852 | Withdrawn

• 1 other identifier: ΕΒΔ427/12-06-2019
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Syndrome; Cardiovascular Risk Factor

Keywords

metabolic syndrome; probiotics; cardiovascular risk factor

Outcome Measures

Primary Outcomes (3)

• IL-1β production by stimulated peripheral blood mononuclear cells.

  We will measure IL-1β concentrations in cell supernatants and consequently the NLRP3 inflammasome activation via the alteration in cytokine production in the presence of a different stimulants.

  12 weeks

• TNFα expression

  Reverse Transcription Polymerase Chain Reaction (RT-PCR) will be used to quantify gene expression of tumor necrosis factor alpha (TNFα)

  12 weeks

• Caspase 1 (CASP1) expression

  Reverse Transcription Polymerase Chain Reaction (RT-PCR) will be used to quantify CASΡ-1 as a key modulator of IL-1b bioactivity.

  12 weeks

Secondary Outcomes (5)

• Glycocalyx thikness.

  12 weeks

• Change of biochemical exams related to MetS

  12 weeks

• Alterations of hsCRP levels.

  12 weeks

• Alterations in gut microbiota

  12 weeks

• Alterations of HbA1C

  12 weeks

Study Arms (2)

Probiotics

ACTIVE COMPARATOR

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.

Dietary Supplement: Probiotic mix

Placebo supplement

PLACEBO COMPARATOR

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.

Dietary Supplement: Placebo

Interventions

Probiotic mix 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.

Probiotics

Placebo DIETARY_SUPPLEMENT

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

Placebo supplement

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Attikon Hospital: lead

Study Sites (1)

Attikon University General Hospital

Athens, 12462, Greece

Location

MeSH Terms

Conditions

Metabolic Syndrome

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Arezina Kasti

  Attikon University General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Clinical Nutrition Department

Study Record Dates

• First Submitted: November 19, 2019
• First Posted: January 18, 2020
• Study Start: June 12, 2019
• Primary Completion: January 26, 2021
• Study Completion: January 26, 2021
• Last Updated: April 7, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)