Gut-level Antiinflammatory Activities of Green Tea in Metabolic Syndrome

Not Applicable

Completed

• Conditions: Inflammation; Dysbiosis; Endotoxemia; Metabolic Syndrome
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Green Tea Extract

• Registration Number: NCT03973996
• Lead Sponsor: Ohio State University

Brief Summary

This study evaluates dietary green tea extract to improve gut health and inflammation in persons with metabolic syndrome and healthy adults. Participants will complete two phases of intervention in random order in which they will consume green tea extract or placebo for one month and then switch to the opposite treatment for an additional month.

Detailed Description

Tea is the most abundantly consumed prepared beverage in the world. Green tea, containing catechins, exerts antiinflammatory activities. However, a fundamental gap exists concerning its intestinal-level targets that can prevent metabolic syndrome (MetS) development and progression. Studies in obese rodents indicate that green tea inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activation by limiting gut-derived endotoxin translocation to the portal circulation and decreasing hepatic Toll-like receptor-4 (TLR4) pro-inflammatory signaling. The objective of this clinical investigation is to establish evidence-based recommendations for green tea, based on improvements in endotoxemia and restored gut barrier function, that promote optimal health. The hypothesis is that green tea catechins function to limit metabolic endotoxemia by ameliorating gut dysbiosis-mediated inflammation that otherwise provokes intestinal permeability. This will be tested by conducting a double-blind, placebo-controlled, randomized-order, crossover trial in MetS and healthy persons to examine the efficacy of green tea on metabolic endotoxemia. Each treatment will be one-month in duration and separated by a washout period. The anticipated outcomes are expected to be of significance, because they will advance a dietary strategy to help avert MetS complications attributed to metabolic endotoxemia by establishing antiinflammatory prebiotic and antimicrobial bioactivities of catechins that promote intestinal health.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-05-30
• Study First Submitted QC: 2019-06-03
• Study First Posted: 2019-06-04
• Study Start: 2019-07-01
• Primary Completion: 2021-03-01
• Study Completion: 2021-03-01
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-16
• Last Update Posted: 2021-12-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants consuming matched gummy confections formulated without green tea extract daily for 4 weeks
Green Tea	Green Tea Extract	Participants consuming gummy confections with catechin-rich green tea extract daily for 4 weeks

Primary Outcome Measures

Name	Time	Method
Change in metabolic endotoxemia	Day 0, 14, and 28 of the 28-day intervention	Serum endotoxin concentration (EU/mL) will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.

Secondary Outcome Measures

Name	Time	Method
Pro-inflammatory gene expression from peripheral blood mononuclear cells	Day 28 of the 28-day intervention	Relative expression of toll-like receptor 4, myeloid differentiation factor 88, p65 subunit of NF-kappa B, interleukin-6, interleukin-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1 will be measured individually at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.
Intestinal inflammatory biomarker: calprotectin	Days 25-27 of the 28-day intervention	Fecal concentration (μg/g) of calprotectin will be measured in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Intestinal inflammatory biomarker: myeloperoxidase	Days 25-27 of the 28-day intervention	Fecal concentration (ng/g) of myeloperoxidase will be measured in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Fecal catechins and their metabolites	Days 25-27 of the 28-day intervention	Fecal concentrations (μmol/kg) of epigallocatechin gallate, epicatechin gallate, epigallocatechin, epicatechin, gamma-valerolactones, and catechin-derivates will be measured individually in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Gut microbiota Firmicutes/Bacteroidetes ratio	Days 25-27 of the 28-day intervention	Gut microbiota Firmicutes/Bacteroidetes ratio will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Change in plasma glucose	Day 0, 14, and 28 of the 28-day intervention	Plasma concentration (mg/dL) of glucose will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Gastrointestinal permeability	Day 28 of the 28-day intervention	Lactulose/mannitol ratio will be measured in urine collected 0-5 h post-ingestion to assess small intestinal permeability. Sucralose (%) will be measured in urine collected 0-24 h post-ingestion to assess colonic permeability. Between-treatment differences will be measured in MetS vs. healthy individuals.
Plasma inflammatory biomarker: C-reactive protein	Day 28 of the 28-day intervention	Plasma concentration (mg/L) of C-reactive protein will be measured at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.
Plasma inflammatory biomarkers: interleukin-6, interleukin-8, and tumor necrosis factor alpha	Day 28 of the 28-day intervention	Plasma concentrations (pg/mL) of interleukin-6, interleukin-8, and tumor necrosis factor alpha will be measured individually at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.
Plasma inflammatory biomarker: myeloperoxidase	Day 28 of the 28-day intervention	Plasma concentration (ng/mL) of myeloperoxidase will be measured at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.
Changes in plasma catechins and their metabolites	Day 0, 14, and 28 of the 28-day intervention	Plasma concentrations (nmol/L) of epigallocatechin gallate, epicatechin gallate, epigallocatechin, epicatechin, gamma-valerolactones, and catechin-derivates will be measured individually at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Fecal short-chain fatty acids	Days 25-27 of the 28-day intervention	Fecal concentrations (mmol/kg) of butyrate, acetate, propionate, isobutyric acid, and isovaleric acid will be measured individually in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Gut microbiota diversity indices	Days 25-27 of the 28-day intervention	Gut microbiota diversity indices (Shannon species and Chao1) will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Gut microbiota relative abundance	Days 25-27 of the 28-day intervention	Gut microbiota relative abundance (% order, genus, and species level) will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Gut microbiota function proportions	Days 25-27 of the 28-day intervention	Gut microbiota function proportions (%) based on microbial genome analysis will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Change in plasma insulin	Day 0, 14, and 28 of the 28-day intervention	Plasma concentration (μIU/mL) of insulin will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Change in plasma lipids	Day 0, 14, and 28 of the 28-day intervention	Plasma concentrations (mg/dL) of triglyceride and HDL-cholesterol will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Changes in serum alanine transaminase and aspartate transaminase	Day 0, 14, and 28 of the 28-day intervention	Serum concentrations (U/L) of alanine transaminase and aspartate transaminase will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Changes in serum creatinine and blood urea nitrogen	Day 0, 14, and 28 of the 28-day intervention	Serum concentrations (U/L) of creatinine and blood urea nitrogen will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Change in blood hematocrit	Day 0, 14, and 28 of the 28-day intervention	Blood hematocrit (%) will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.

Trial Locations

Locations (1)

The Ohio State University; 🇺🇸 Columbus, Ohio, United States