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

NCT06092060 | Completed

• 1 other identifier: PoznanUPhyEd Probiotyk
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Insulin Resistance

Keywords

Insulin Resistance; Multistrain Probiotic; Gut Microbiota

Outcome Measures

Primary Outcomes (11)

• 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

• 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

• 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

• 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

• 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

• 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

• Transcription factors regulating carbohydrate and lipid metabolism

  Peroxisome proliferator-activated receptor (PPARγ; NR1C3), PPARγ coactivator, coactivator 1 α ( PGC -1α)

  up to 10 months

• 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

• 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

• 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

• Indicators of a disrupted intestinal barrier in the blood

  zonulin, intestinal fatty acid binding protein (I-FABP)

  up to 10 months

Secondary Outcomes (4)

• Gastrointestinal disorders questionnaire

  up to 10 months

• Body mass analysis (BMI, kg/m^2)

  up to 10 months

• Body composition analysis (percent of total body mass

  up to 10 months

• Composite measure of Diet composition assessed by food diaries

  up to 10 months

Study Arms (2)

the group GS

EXPERIMENTAL

probiotic treatment group, ca. 20 participants

Dietary Supplement: the group GS (probiotic)

the group GP

PLACEBO COMPARATOR

placebo group, ca. 20 participants

Dietary Supplement: the group GP (placebo)

Interventions

the group GS (probiotic) DIETARY_SUPPLEMENT

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 GS

the group GP (placebo) DIETARY_SUPPLEMENT

The placebo group will receive 2 capsules consisting of the probiotic product carrier, which is corn starch and maltodextrin, twice a day, 3-month.

the group GP

Eligibility Criteria

• Age: 25 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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,
• nd 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).

Sponsors & Collaborators

• Poznan University of Physical Education: lead

Study Sites (1)

Poznan University of Physical Education

Poznan, 61-871, Poland

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Probiotics

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Joanna Karolkiewicz, Prof

  Poznan University of Physical Education

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: October 23, 2023
• Study Start: April 1, 2021
• Primary Completion: February 1, 2022
• Study Completion: July 20, 2023
• Last Updated: October 23, 2023

Record last verified: 2023-07

Locations

PL (1)