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临床试验/NCT03860584
NCT03860584已完成不适用

Alleviation Of Metabolic Endotoxemia In Adults With Metabolic Syndrome With Milk Fat Globule Membrane

Ohio State University2 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2019年7月1日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
30
试验地点
2
主要终点
Serum Endotoxin

研究概览

简要总结

Metabolic syndrome (MetS) adults (n = 24; 18-65 y) will be enrolled to complete a 2-arm, double-blind, randomized controlled, crossover trial. They will be randomized in 4-unit blocks to receive, for 13 d, a controlled diet with dairy milk (3.5% fat; 3 servings/d) enriched with milk fat globule membrane (MFGM, MEB) or a matched dairy milk that instead contains soy lecithin/phospholipid (control, COMP). All foods during each study period will be provided to ensure weight maintenance and to increase homogeneity of gut and host responses. Anthropometrics and blood pressure will be assessed at days 0, 7, and 13. Prior to (day 0) and after each 2-wk arm (day 13), a fasting blood sample will be collected to assess serum endotoxin and metabolic chemistries (glucose, lipids, insulin), and Toll-like receptor 4 /nuclear factor kappaB (TLR4/NFκB)-dependent genes from whole blood. A breath sample will be collected to assess the correlation analysis of plasma metabolic biomarkers. After the 2-week intervention, from fecal samples collected on day 13, the investigators will assess microbiota composition and function, short chain fatty acids (SCFA), and intestinal inflammatory markers (calprotectin, myeloperoxidase). On d 13, participants in the fasted state will receive a high-fat/high-glucose meal challenge to induce gut-derived endotoxin translocation. At 30-minute intervals for 3-hour, the investigators will evaluate circulating endotoxin, glucose, and insulin; TLR4/NFκB-dependent genes will be assessed from whole blood at 0 hour and 3-hour. Gut permeability probes will be co-administered with the test meal challenge, and 24-hour urine will be collected to assess gut barrier integrity. Participants will then undergo a 2-week washout prior to receiving the alternative treatment and completing all procedures in an identical manner.

详细描述

Background and hypothesis:

Our preclinical evidence shows that phospholipid-rich milk fat globule membrane (MFGM) attenuates lipopolysaccharide-induced increases in gut permeability and pro-inflammatory cytokines. MFGM also attenuates inflammation in association with a prebiotic and/or antimicrobial activity that modulates microbiota composition. Our central hypothesis is that MFGM-enriched dairy milk compared with a matched milk beverage containing soy lecithin (control) decreases metabolic endotoxemia and improves glucose tolerance in metabolic syndrome (MetS) adults by increasing gut barrier integrity in association with alleviating gut dysbiosis and inflammation.

Study Design:

The investigators will enroll male and female MetS adults (n = 24; 18-65 y) to complete a 2-arm, double-blind, randomized controlled, crossover trial. They will be randomized in 4-unit blocks to receive, for 14 days, a controlled diet with dairy milk (3.5% fat; 3 servings/d) enriched with MFGM-derived phospholipid or a matched dairy milk that instead contains coconut and palm oil (control). The investigators will provide all foods during each study period to ensure weight maintenance and to increase homogeneity of gut and host responses.

Subjects:

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Crossover
主要目的
Prevention
盲法
Double (Participant, Outcomes Assessor)

盲法说明

Both participants and key research personnel will be blinded between MFGM-enriched full-fat dairy milk (treatment) and milk with soy phospholipid/lecithin (control).

入排标准

年龄范围
18 Years 至 65 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Serum Glucose 100-126 mg/dl
  • Waist C >89/102 cm; F/M
  • Serum HDL-C: <50/40 mg/dl; F/M
  • Serum triglyceride: >150 mg/dl
  • Blood Pressure >130/85 mmHg

排除标准

  • Unstable body mass (±2 kg over prior 3-mo)
  • Vegetarian
  • Food allergies or lactose intolerance
  • User of dietary supplements or probiotics (within past 1-mo)
  • Pregnancy, lactation, changes in birth control (within 6-mo)
  • Any gastrointestinal disorders
  • Chronic diarrhea
  • Excess alcohol (>2 drinks/d)
  • Excess aerobic exercise (>5 h/wk)
  • Recent antibiotic or anti-inflammatory agent use
  • Blood Pressure >140/90 mmHg

结局指标

主要结局

Serum Endotoxin

时间窗: Day 13 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge)

Data are biomarker area under the time-concentration curve (0-3 hours) on day 13

次要结局

  • Urine Sucralose/Erythritol(5-24 hours)
  • Plasma Glucose(Day 13)
  • Plasma Insulin(day 13 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge))
  • Plasma HDL-C(Day 13)
  • Plasma Triglyceride(Day 13)
  • Plasma Total Cholesterol(Day 13)
  • Plasma Glucagon-like Peptide-1(Day 13)
  • Urine Lactulose/Mannitol(Day 13)
  • Urine Sucralose/Erythritol(5-24 hours)
  • Fecal Acetate(Day 13)
  • Fecal Butyrate(Day 13)
  • Fecal Propionate(Day 13)
  • Plasma Gastric Inhibitory Polypeptide(Day 13)
  • Fecal Calprotectin(Day 13)
  • Fecal Myeloperoxidase(Day 13)
  • Whole-blood Messenger RNA Expression of Toll-like Receptor-4 at Fasting(Day 13)
  • Whole-blood Messenger RNA Expression of Interleukin-6 at Fasting(Day 13)
  • Whole Blood Messenger RNA Expression of Tumor Necrosis Factor-alpha at Fasting(Day 13)
  • Whole Blood Messenger RNA Expression of Toll-like Receptor-4 at 3 h Post-meal Challenge(Day 13, 3 h post-meal)
  • Whole Blood Messenger RNA Expression of Interleukin-6 at 3 h Post-meal Challenge(Day 13, 3 h post-meal)
  • Whole Blood Messenger RNA Expression of Tumor Necrosis Factor-alpha at 3 h Post-meal Challenge(Day 13, 3 h post-meal)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Richard Bruno

Professor and Principal Investigator

Ohio State University

研究点 (2)

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