Dietary Green Tea Confection For Resolving Gut Permeability-Induced Metabolic Endotoxemia In Obese Adults

Study Overview
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Brief Summary
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This study is focused on assessing gastrointestinal-level improvements by which green tea limits metabolic endotoxemia. It is expected that catechin-rich green tea will improve gut barrier function to prevent endotoxin translocation and associated low-grade inflammation. Outcomes will therefore support dietary recommendations for green tea to alleviate obesity-related inflammatory responses. Specifically, the study is expected to demonstrate that a green tea confection snack food can attenuate metabolic endotoxemia in association with restoring gastrointestinal health.

Detailed Description
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Obesity is a major public health concern in the United States, with over two-thirds of the adult population classified as overweight or obese. Obesity is characterized by low-grade chronic inflammation that, in part, is mediated by metabolic endotoxemia. Metabolic endotoxemia describes increased circulating levels of gut-derived endotoxin (a bacterial product derived from Gram-negative bacteria in the intestines) that results from gut barrier dysfunction, a phenomenon that is common in obesity. Studies in rodents models have shown that dietary supplementation with green tea extract (GTE) reduces metabolic endotoxemia in association with improved gut health. This clinical trial will therefore investigate the extent to which a green tea confection snack food can alleviate metabolic endotoxemia and restore gut health in obese humans. It is hypothesized that 4-week daily ingestion of a green tea extract (GTE)-rich confection will limit metabolic endotoxemia by decreasing gut barrier permeability. This study will address the following objectives: 1) define alterations in catechin pharmacokinetics in obese compared with healthy adults, 2) demonstrate improvements in gut barrier function by GTE, and 3) demonstrate GTE-mediated amelioration of microbial dysbiosis. To test the hypothesis, all participants will complete a 12-h pharmacokinetics study to define the influence of obesity on catechin bioavailability and metabolism. They will then complete a double-blind, randomized, placebo-controlled trial where they will receive a GTE-rich or placebo confection for 4 weeks. Prior to and upon completing the intervention, participants will undergo a gut permeability test, fecal samples will be collected for microbiota composition analysis, and blood samples will be collected to assess endotoxin and inflammatory biomarkers. Upon successfully completing this study, it is anticipated that chronic consumption of a green tea confection will be demonstrated to be an effective dietary strategy to reduce metabolic endotoxemia and improve gut health.

Official Title
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Dietary Green Tea Confection For Resolving Gut Permeability-Induced Metabolic Endotoxemia In Obese Adults

Conditions
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Obesity, Endotoxemia, Inflammation

Intervention / Treatment
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* Other: Green Tea Extract
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overweight/obese (BMI = 28-40 kg/m2) Fasting glucose < 126 mg/dL Normotensive (blood pressure < 140/90 mmHg) Non-dietary supplement user Non-smoker Exclusion Criteria: Regular tea drinkers (> 2 cups/week) Vegetarians Use of medications to manage diabetes, hypertension, or hyperlipidemia Use of any medications known to be contraindicated for use with green tea ingestion User of dietary supplements, prebiotics, or probiotics Recent use of antibiotics or anti-inflammatory agents Women who are pregnant or lactating or have initiated or changed birth control in the past 3-months Individuals with gastrointestinal disorders or surgeries Individuals with hemochromatosis Alcohol intake > 3 drinks per day Any history of cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Confection<br>Confection without green tea extract consumed daily for 4 weeks | Other: Placebo<br>* Confections containing no green tea extract that will be ingested daily for 4 weeks<br>|
| Experimental: Green Tea Extract-Confection<br>Confection with green tea extract consumed daily for 4 weeks | Other: Green Tea Extract<br>* Confections containing green tea extract that will be ingested daily for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endotoxin | Serum endotoxin concentration | Week 0 - Fasting | 
| Endotoxin | Serum endotoxin concentration | Week 2 - Fasting | 
| Endotoxin | Serum endotoxin concentration | Week 4 - Fasting | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut Permeability - Lactulose to Mannitol Ratio | Ratio of excretion of urinary sugars | Week 0 - 0-5 hours | 
| Gut Permeability - Lactulose to Mannitol Ratio | Ratio of excretion of urinary sugars | Week 0 - 6-24 hours | 
| Gut Permeability - Lactulose to Mannitol Ratio | Ratio of excretion of urinary sugars | Week 4 - 0-5 hours | 
| Gut Permeability - Lactulose to Mannitol Ratio | Ratio of excretion of urinary sugars | Week 4 - 6-24 hours | 
| Gut Permeability - Sucralose to Erythritol Ratio | Ratio of excretion of urinary sugars | Week 0 - 0-5 hours | 
| Gut Permeability - Sucralose to Erythritol Ratio | Ratio of excretion of urinary sugars | Week 0 - 6-24 hours | 
| Gut Permeability - Sucralose to Erythritol Ratio | Ratio of excretion of urinary sugars | Week 4 - 0-5 hours | 
| Gut Permeability - Sucralose to Erythritol Ratio | Ratio of excretion of urinary sugars | Week 4 - 6-24 hours | 
| Firmicutes to Bacteroidetes Ratio - Microbiota | Ratio of relative abundances of Firmicutes to Bacteroidetes in feces | Week 0 | 
| Firmicutes to Bacteroidetes Ratio - Microbiota | Ratio of relative abundances of Firmicutes to Bacteroidetes in feces | Week 4 | 
| Bioavailability - Epigallocatechin gallate | Area under the curve (AUC) of plasma catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of a green tea confection | 
| Bioavailability - Epigallocatechin | Area under the curve (AUC) of plasma catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of a green tea confection | 
| Bioavailability - Epicatechin gallate | Area under the curve (AUC) of plasma catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of a green tea confection | 
| Bioavailability - Epicatechin | Area under the curve (AUC) of plasma catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of a green tea confection | 
| Cmax of Epigallocatechin gallate | Maximum plasma concentration of catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of green tea confection | 
| Cmax of Epigallocatechin | Maximum plasma concentration of catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of green tea confection | 
| Cmax of Epicatechin gallate | Maximum plasma concentration of catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of green tea confection | 
| Cmax of Epicatechin | Maximum plasma concentration of catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of green tea confection | 
| Tmax of Epigallocatechin gallate | Time to maximal plasma concentration of catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of green tea confection | 
| Tmax of Epigallocatechin | Time to maximal plasma concentration of catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of green tea confection | 
| Tmax of Epicatechin gallate | Time to maximal plasma concentration of catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of green tea confection | 
| Tmax of Epicatechin | Time to maximal plasma concentration of catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection | 0-12 hours post-ingestion of green tea confection | 
| Calprotectin | Fecal calprotectin concentration | Week 0 | 
| Calprotectin | Fecal calprotectin concentration | Week 4 |