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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammation; Obesity; Endotoxemia
• Intervention / Treatment: Other: Placebo; Other: Green Tea Extract

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 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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo Confection; Confection without green tea extract consumed daily for 4 weeks	Other: Placebo; Confections containing no green tea extract that will be ingested daily for 4 weeks
EXPERIMENTAL: Green Tea Extract-Confection; Confection with green tea extract consumed daily for 4 weeks	Other: Green Tea Extract; Confections containing green tea extract that will be ingested daily for 4 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ohio State University

Publications and helpful links

General Publications

• Li J, Sapper TN, Mah E, Moller MV, Kim JB, Chitchumroonchokchai C, McDonald JD, Bruno RS. Green tea extract treatment reduces NFkappaB activation in mice with diet-induced nonalcoholic steatohepatitis by lowering TNFR1 and TLR4 expression and ligand availability. J Nutr Biochem. 2017 Mar;41:34-41. doi: 10.1016/j.jnutbio.2016.12.007. Epub 2016 Dec 21.
• Li J, Sasaki GY, Dey P, Chitchumroonchokchai C, Labyk AN, McDonald JD, Kim JB, Bruno RS. Green tea extract protects against hepatic NFkappaB activation along the gut-liver axis in diet-induced obese mice with nonalcoholic steatohepatitis by reducing endotoxin and TLR4/MyD88 signaling. J Nutr Biochem. 2018 Mar;53:58-65. doi: 10.1016/j.jnutbio.2017.10.016. Epub 2017 Nov 3.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 29, 2018
• Primary Completion (ANTICIPATED): March 30, 2022
• Study Completion (ANTICIPATED): March 30, 2023

Study Registration Dates

• First Submitted: January 22, 2018
• First Submitted That Met QC Criteria: January 22, 2018
• First Posted (ACTUAL): January 29, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 7, 2021
• Last Update Submitted That Met QC Criteria: December 4, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Sepsis; Bacteremia; Toxemia; Inflammation; Endotoxemia
• Other Study ID Numbers: 2017H0246

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data will be published as aggregate only. Data sharing may be possible pending institutional agreements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No