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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Indicators of a disrupted intestinal barrier in the blood
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 25 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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,
- •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.
结局指标
主要结局
Indicators of a disrupted intestinal barrier in the blood
时间窗: up to 10 months
zonulin, intestinal fatty acid binding protein (I-FABP)
Adipokines and myokines
时间窗: up to 10 months
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)
Indicators of inflammation
时间窗: up to 10 months
C-reactive protein (hsCRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF-alpha), lipocalin-2
Indicators of insulin sensitivity and carbohydrate metabolism
时间窗: up to 10 months
Analysis of biochemical indicators related to insulin resistance such as concentrations of glucose, insulin, insulin-like growth factor (IGF-1), hemoglobin A1C (HgA1C), myoglobin
Evaluation of indicators in stool
时间窗: up to 10 months
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).
Intestinal metabolome in stool samples
时间窗: up to 10 months
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)
Indicators of vascular endothelial function
时间窗: up to 10 months
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)
Qualitative assessment of intestinal microbiota in stool samples
时间窗: up to 10 months
gut bacteria species in stool will be assessed using the shallow shotgun sequencing method, NGS (Next Generation Sequencing)
Transcription factors regulating carbohydrate and lipid metabolism
时间窗: up to 10 months
Peroxisome proliferator-activated receptor (PPARγ; NR1C3), PPARγ coactivator, coactivator 1 α ( PGC -1α)
Quantitive change in intestinal microbiota in stool samples
时间窗: up to 10 months
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
Indicators of lipid metabolism
时间窗: up to 10 months
Concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, oxidatively modified LDL lipoprotein (oxLDL), paraoxonase (PON) activity, proprotein convertase subtilisin/kexin 9 (PCSK-9)
次要结局
- Body mass analysis (BMI, kg/m^2)(up to 10 months)
- Composite measure of Diet composition assessed by food diaries(up to 10 months)
- Gastrointestinal disorders questionnaire(up to 10 months)
- Body composition analysis (percent of total body mass(up to 10 months)