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

Metabolic Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04232852
• Other study ID #: ???427/12-06-2019
• Status: Withdrawn
• Phase: N/A
• Start date: June 12, 2019
• Est. completion date: January 26, 2021

Study information

• Verified date: March 2022
• Source: Attikon Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 26, 2021
• Est. primary completion date: January 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Risk Factor
• Inflammation
• Metabolic Syndrome
• Syndrome

Intervention

Dietary Supplement:
• 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.
• Placebo
Patients in the placebo group will receive an identical capsule of maltodextrin.

Locations

Country	Name	City	State
Greece	Attikon University General Hospital	Athens

Sponsors (1)

Lead Sponsor	Collaborator
Attikon Hospital

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IL-1ß production by stimulated peripheral blood mononuclear cells.	We will measure IL-1ß 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
Primary	TNFa expression	Reverse Transcription Polymerase Chain Reaction (RT-PCR) will be used to quantify gene expression of tumor necrosis factor alpha (TNFa)	12 weeks
Primary	Caspase 1 (CASP1) expression	Reverse Transcription Polymerase Chain Reaction (RT-PCR) will be used to quantify CAS?-1 as a key modulator of IL-1b bioactivity.	12 weeks
Secondary	Glycocalyx thikness.	The Perfused Boundary Region (PBR) of the hypoglossal vessels will be calculated using a high-resolution special lens using the Sideview DarkField (SDF) Imaging technique (Microscan, Glucockeck).	12 weeks
Secondary	Change of biochemical exams related to MetS	Insulin resistance (IR) will be quantified using the HOMA-IR index (HOmeostatic Model Assessment, HOMA-IR index), calculated as the product of fasting plasma insulin. Blood lipids (Total Cholesterol, LDL-C, HDL-C, TRG) will be measured by enzymatic methods.	12 weeks
Secondary	Alterations of hsCRP levels.	Hs-CRP will be measured by the Immunoturbidimetry method with a polyclonal antibody.	12 weeks
Secondary	Alterations in gut microbiota	Stool specimen will be collected before and after intervention. Stool samples will be frozen (-80 ° C) immediately after collection, in order to study changes in the gut microbiota by the technique of deep sequencing at a second time.	12 weeks
Secondary	Alterations of HbA1C	HbA1C will be measured by the HPLC.	12 weeks