The Effect of a Multistrain Probiotic on Metformin Tolerance and Efficacy With Microbiota and Stool Metabolome in Insulin-resistant Women - a 12-week Randomized, Placebo-controlled, Double-blind Study

Insulin Resistance Clinical Trial

Official title:

The Effect of a Multi-strain Probiotic Consisting of: Bifidobacterium Lactis W52, Lactobacillus Brevis W63, Lactobacillus Casei W56, Lactococcus Lactis W19, Lactococcus Lactis W58, Lactobacillus Acidophilus W37, Bifidobacterium Bifidum W23, Bifidobacterium Lactis W51, and Lactobacillus Salivarius W24 on Metformin Tolerance and Efficacy With Microbiota and Stool Metabolome in Insulin-resistant Women - a 12-week Randomized, Placebo-controlled, Double-blind Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06092060
• Other study ID #: PoznanUPhyEd Probiotyk
• Status: Completed
• Phase: N/A
• Start date: April 1, 2021
• Est. completion date: July 20, 2023

Study information

• Verified date: July 2023
• Source: Poznan University of Physical Education
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to evaluate the efficacy of metformin on insulin sensitivity and vascular endothelial function with respect to gut microbiota and metabolome in women with established insulin resistance and its tolerance after 12 weeks of probiotic therapy.

The hypothesis is probiotic therapy in women with established insulin resistance undergoing metformin treatment increases the drug's efficacy to improve insulin sensitivity and intestinal endothelial function, and reduces gastrointestinal side effects.

Study participants will be randomly assigned to 2 groups, taking a probiotic (GS) or a placebo (GP). The randomization scheme will be computer-generated using permuted blocks of block size 4.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 20, 2023
• Est. primary completion date: February 1, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 45 Years

Eligibility

Inclusion Criteria:

• women 25-45 years old, menstruating, BMI 25-32.9 kg / m2, insulin resistance based on the HOMA-IR index (cut-off point 2.5

Exclusion Criteria:

• type 1 and 2 diabetes,

• poorly controlled arterial hypertension (mean SBP values> 140mmHg and / or mean DBP values> 90mmHg) within the last month and / or the need to modify pharmacological treatment,

• 2nd degree obesity, BMI> 35 kg / m2,

• lipid disorders requiring pharmacological treatment in the last 3 months before the start of observation or during observation,

• positive history of ischemic heart disease, carotid and / or lower limb atherosclerosis,

• features of heart failure on physical examination and / or additional examinations (chest X-ray, echocardiography),

• clinically significant arrhythmias or conduction disturbances,

• chronic kidney disease with creatinine clearance <60mL / min / 1.73m2,

• clinically significant impairment of liver function (transaminase values 3 times the normal range),

• acute or chronic, clinically evident inflammatory process (diseases of connective tissue and joints, inflammatory processes of the respiratory tract, inflammatory processes of the genitourinary system, inflammation of the head and neck),

• acute infection in the last month,

• Cancer,

• alcohol abuse, drug addiction,

• taking medications that may interfere with test results,

• Taking antibiotics, steroids, antifungal and antiparasitic agents 4 weeks before the examination (not applicable to topical antifungal agents).

• taking pre - and / or probiotics in the last 12 weeks before the test

• travel to tropical countries in the last 4 weeks prior to the survey

• other conditions that may pose any risk to the patient during the follow-up.

Related Conditions & MeSH terms

• Insulin Resistance

Intervention

Dietary Supplement:
• the group GS (probiotic)
The probiotic-supplemented group will receive 2 capsules of freeze-dried powder of a probiotic mixture containing the following bacterial strains twice a day, 3-month: Bifidobacterium lactis W52, Lactobacillus brevis W63, Lactobacillus casei W56, Lactococcus lactis W19, Lactococcus lactis W58, Lactobacillus acidophilus W37, Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Lactobacillus salivarius W24
• the group GP (placebo)
The placebo group will receive 2 capsules consisting of the probiotic product carrier, which is corn starch and maltodextrin, twice a day, 3-month.

Locations

Country	Name	City	State
Poland	Poznan University of Physical Education	Poznan

Sponsors (1)

Lead Sponsor	Collaborator
Poznan University of Physical Education

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Qualitative assessment of intestinal microbiota in stool samples	gut bacteria species in stool will be assessed using the shallow shotgun sequencing method, NGS (Next Generation Sequencing)	up to 10 months
Primary	Quantitive change in intestinal microbiota in stool samples	determination of quantitative (Colony forming units - CFU) changes in bacteria in the stool - the shallow shotgun sequencing method, NGS (Next Generation Sequencing) molecular analysis will be used to assess the changes	up to 10 months
Primary	Intestinal metabolome in stool samples	metabolomic analysis (endogenous metabolism (catabolism of amino acids, lipids), biotransformation products under the influence of xenobiotics (e.g., caffeine), fatty acid biosynthesis, fatty acid derivatives, glycolysis, gluconeogenesis, biosynthesis of primary bile acids, amino acid metabolism, sphingolipid metabolism, unknown metabolites, non-targeted metabolome, short-chain fatty acids) will be performed on a quadrupole mass spectrometer coupled with a time-of-flight (QToF) analyzer connected to the AB Sciex - TripleTOF® 6600+ high performance liquid chromatograph (UHPLC)	up to 10 months
Primary	Indicators of insulin sensitivity and carbohydrate metabolism	Analysis of biochemical indicators related to insulin resistance such as concentrations of glucose, insulin, insulin-like growth factor (IGF-1), hemoglobin A1C (HgA1C), myoglobin	up to 10 months
Primary	Evaluation of indicators in stool	Determination of intestinal inflammatory index - fecal calprotectin, determination of intestinal permeability index - fecal zonulin and determination of intestinal membrane inflammatory index sIgA in feces (RT-PCR and Western blotting).	up to 10 months
Primary	Indicators of lipid metabolism	Concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, oxidatively modified LDL lipoprotein (oxLDL), paraoxonase (PON) activity, proprotein convertase subtilisin/kexin 9 (PCSK-9)	up to 10 months
Primary	Transcription factors regulating carbohydrate and lipid metabolism	Peroxisome proliferator-activated receptor (PPAR?; NR1C3), PPAR? coactivator, coactivator 1 a ( PGC -1a)	up to 10 months
Primary	Adipokines and myokines	Analysis of biochemical indicators related to insulin resistance such as leptin, adiponectin, resistin, wisfatin, retinol-binding protein type 4 (RBP4), lipocalin-2, proprotein convertase subtilisin/kexin type 9 (PCSK9)	up to 10 months
Primary	Indicators of inflammation	C-reactive protein (hsCRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF-alpha), lipocalin-2	up to 10 months
Primary	Indicators of vascular endothelial function	Analysis of biochemical indicators related to insulin resistance and endothelial function, such as endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), homocysteine, plasminogen activator inhibitor 1 (PAI-1), adhesion molecules (sVCAM-1, ICAM-1), monocyte chemoattractant 1(MCP-1), matrix metalloproteinases (MMP-9 and MMP-2), cytosolic fatty acid binding proteins (FABPs)	up to 10 months
Primary	Indicators of a disrupted intestinal barrier in the blood	zonulin, intestinal fatty acid binding protein (I-FABP)	up to 10 months
Secondary	Gastrointestinal disorders questionnaire	assessment of gastrointestinal disorders using the Rome IV Questionnaire for adults (selected questions on irritable bowel syndrome, constipation and diarrhea); the statements of the questionnaire relate to frequency and intensity of disorders; higher scores mean worse outcome	up to 10 months
Secondary	Body mass analysis (BMI, kg/m^2)	determination of body weight and composition using the electrical bioimpedance method	up to 10 months
Secondary	Body composition analysis (percent of total body mass	assessment of bone, fat and fat-free mass using the electrical bioimpedance method	up to 10 months
Secondary	Composite measure of Diet composition assessed by food diaries	assessment of protein, fat, carbohydrates, fibre, minerals and vitamins intake using food diaries (grams)	up to 10 months