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

Not Applicable

Completed

Conditions: Obesity
Endotoxemia
Inflammation

Interventions: Other: Placebo
Other: Green Tea Extract

Registration Number: NCT03413735

Lead Sponsor: Ohio State University

Brief Summary: This study is focused on assessing gastrointestinal-level improvements by which green tea limits metabolic endotoxemia. It is completed in two phases. Phase I consists of a pharmacokinetic study to examine the bioavailability of green tea catechins among lean and obese persons who consumed a single dose of a green tea extract (GTE)-containing confection. These persons will then complete phase 2, which consists of a parallel design randomized controlled in which lean and obese persons will consume placebo or GTE confections.

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: 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 initially complete a 12-h pharmacokinetics study to define the influence of obesity on catechin bioavailability and metabolism. They will then be randomized to 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Confection	Placebo	Confection without green tea extract consumed daily for 4 weeks
Green Tea Extract-Confection	Green Tea Extract	Confection with green tea extract consumed daily for 4 weeks

Primary Outcome Measures

Name	Time	Method
Endotoxin	Week 4 - Fasting	Serum endotoxin concentration

Secondary Outcome Measures

Name	Time	Method
Calprotectin	Week 4	Fecal calprotectin concentration
Gut Permeability - Lactulose to Mannitol Ratio	Week 4 - 6-24 hours	Urinary Lactulose/Mannitol Ratio (mg/mg)
Gut Permeability - Sucralose to Erythritol Ratio	Week 4 - 0-24 hours	Urinary Sucralose/Erythritol Ratio (mg/mg)
Urinary Sucralose/Erythritol Ratio (mg/mg)	Week 4 - 6-24 hours	Ratio of excretion of urinary sugars (Sucralose to Erythritol)
Firmicutes to Bacteroidetes Ratio - Microbiota	Week 4	Ratio of fecal relative Firmicutes (% abundance)/Bacteroidetes (% abundance)
Bioavailability - Epigallocatechin Gallate	Prior to intervention enrollment...0-12 hours post-ingestion of a green tea confection	Area under the curve (AUC) of plasma epigallocatechin calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection. Epigallocatechin gallate is measured in umol/L over time (hours) resulting in the AUC.
Bioavailability - Epigallocatechin	Prior to intervention enrollment...0-12 hours post-ingestion of a green tea confection	Area under the curve (AUC) of plasma epigallocatechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection. Epigallocatechin is measured in umol/L over time (hours) resulting in the AUC.
Bioavailability - Epicatechin Gallate	Prior to the intervention enrollment...0-12 hours post-ingestion of a green tea confection	Area under the curve (AUC) of plasma epicatechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection. Epicatechins is measured in umol/L over time (hours) resulting in the AUC.
Bioavailability - Epicatechin	Prior to intervention enrollment...0-12 hours post-ingestion of a green tea confection	Area under the curve (AUC) of plasma epicatechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection. Epicatechin is measured in umol/L over time (hours) resulting in the AUC.
Cmax of Epigallocatechin Gallate	Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection	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
Cmax of Epigallocatechin	Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection	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
Cmax of Epicatechin Gallate	Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection	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
Cmax of Epicatechin	Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection	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
Tmax of Epigallocatechin Gallate	Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection	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
Tmax of Epigallocatechin	Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection	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
Tmax of Epicatechin Gallate	Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection	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
Tmax of Epicatechin	Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection	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