Metabolic SyndromeNCT04232852
Probiotics and Systemic Inflammation in Patients With Metabolic Syndrome and High Cardiovascular Risk
A study testing Probiotic mix in people with Metabolic Syndrome and Cardiovascular Risk Factor, run by Attikon Hospital at 1 site in Greece.
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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Metabolic Syndrome, Cardiovascular Risk Factor
- What is being tested?
- Probiotic mix
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteGreece
- Study dates
- 12 Jun 2019to 26 Jan 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Probiotic mix, Placebo
- Keywords
- metabolic syndrome, probiotics, cardiovascular risk factor
- Medical subject headings
- Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotic mixDietary 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.
PlaceboDietary supplement
Patients in the placebo group will receive an identical capsule of maltodextrin.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
TNFα expression
Reverse Transcription Polymerase Chain Reaction (RT-PCR) will be used to quantify gene expression of tumor necrosis factor alpha (TNFα)
Measured: 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.
Measured: 12 weeks
Secondary outcomes (5)
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).
Measured: 12 weeks
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.
Measured: 12 weeks
Alterations of hsCRP levels.
Hs-CRP will be measured by the Immunoturbidimetry method with a polyclonal antibody.
Measured: 12 weeks
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.
Measured: 12 weeks
Alterations of HbA1C
HbA1C will be measured by the HPLC.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start12 Jun 2019
- Primary completion26 Jan 2021
- Study completion26 Jan 2021
Why it stopped: lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Attikon Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Arezina Kasti, Attikon Hospital
- Investigators
- Arezina Kasti, Principal investigator, Attikon University General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04232852
- Sponsor's protocol ID
- ΕΒΔ427/12-06-2019
- Status last verified
- Mar 2022
- First submitted
- 19 Nov 2019
- Last updated
- 7 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Probiotics and Systemic Inflammation in Patients With Metabolic Syndrome and High Cardiovascular Risk
- ClinicalTrials.gov ID
- NCT04232852
- Acronym / sponsor ID
- ΕΒΔ427/12-06-2019
- Conditions
- Metabolic Syndrome, Cardiovascular Risk Factor
- Keywords
- metabolic syndrome, probiotics, cardiovascular risk factor
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Attikon HospitalUniversity, hospital or other
- Study start
- 12 Jun 2019 (actual)
- Primary completion
- 26 Jan 2021 (actual)
- Study completion
- 26 Jan 2021 (actual)
- First posted
- 18 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotics | Active comparator | Dietary Supplement: Probiotic mixDemographics, 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. |
| Placebo supplement | Placebo comparator | Dietary Supplement: PlaceboDemographics, 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotic mixThe 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. | Dietary supplement | Probiotics |
| PlaceboPatients in the placebo group will receive an identical capsule of maltodextrin. | Dietary supplement | Placebo supplement |
Primary outcome
IL-1β production by stimulated peripheral blood mononuclear cells.
Time frame: 12 weeks
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.
TNFα expression
Time frame: 12 weeks
Reverse Transcription Polymerase Chain Reaction (RT-PCR) will be used to quantify gene expression of tumor necrosis factor alpha (TNFα)
Caspase 1 (CASP1) expression
Time frame: 12 weeks
Reverse Transcription Polymerase Chain Reaction (RT-PCR) will be used to quantify CASΡ-1 as a key modulator of IL-1b bioactivity.
5 secondary outcomes
Glycocalyx thikness.
Time frame: 12 weeks
Change of biochemical exams related to MetS
Time frame: 12 weeks
Alterations of hsCRP levels.
Time frame: 12 weeks
Alterations in gut microbiota
Time frame: 12 weeks
Alterations of HbA1C
Time frame: 12 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arezina Kasti principal investigator
Attikon University General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic mix in people with Metabolic Syndrome and Cardiovascular Risk Factor, run by Attikon Hospital at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 7 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IL-1β production by stimulated peripheral blood mononuclear cells. (time frame: 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2022.