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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03413735
• Other study ID #: 2017H0246
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 29, 2018
• Est. completion date: March 30, 2023

Study information

• Verified date: December 2021
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: March 30, 2023
• Est. primary completion date: March 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Endotoxemia
• Inflammation
• Obesity

Intervention

Other:
• Green Tea Extract
Confections containing green tea extract that will be ingested daily for 4 weeks
• Placebo
Confections containing no green tea extract that will be ingested daily for 4 weeks

Locations

Country	Name	City	State
United States	Ohio State University	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University

Country where clinical trial is conducted

United States, 

References & Publications (2)

Li J, Sapper TN, Mah E, Moller MV, Kim JB, Chitchumroonchokchai C, McDonald JD, Bruno RS. Green tea extract treatment reduces NF?B 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. — View Citation

Li J, Sasaki GY, Dey P, Chitchumroonchokchai C, Labyk AN, McDonald JD, Kim JB, Bruno RS. Green tea extract protects against hepatic NF?B 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endotoxin	Serum endotoxin concentration	Week 0 - Fasting
Primary	Endotoxin	Serum endotoxin concentration	Week 2 - Fasting
Primary	Endotoxin	Serum endotoxin concentration	Week 4 - Fasting
Secondary	Gut Permeability - Lactulose to Mannitol Ratio	Ratio of excretion of urinary sugars	Week 0 - 0-5 hours
Secondary	Gut Permeability - Lactulose to Mannitol Ratio	Ratio of excretion of urinary sugars	Week 0 - 6-24 hours
Secondary	Gut Permeability - Lactulose to Mannitol Ratio	Ratio of excretion of urinary sugars	Week 4 - 0-5 hours
Secondary	Gut Permeability - Lactulose to Mannitol Ratio	Ratio of excretion of urinary sugars	Week 4 - 6-24 hours
Secondary	Gut Permeability - Sucralose to Erythritol Ratio	Ratio of excretion of urinary sugars	Week 0 - 0-5 hours
Secondary	Gut Permeability - Sucralose to Erythritol Ratio	Ratio of excretion of urinary sugars	Week 0 - 6-24 hours
Secondary	Gut Permeability - Sucralose to Erythritol Ratio	Ratio of excretion of urinary sugars	Week 4 - 0-5 hours
Secondary	Gut Permeability - Sucralose to Erythritol Ratio	Ratio of excretion of urinary sugars	Week 4 - 6-24 hours
Secondary	Firmicutes to Bacteroidetes Ratio - Microbiota	Ratio of relative abundances of Firmicutes to Bacteroidetes in feces	Week 0
Secondary	Firmicutes to Bacteroidetes Ratio - Microbiota	Ratio of relative abundances of Firmicutes to Bacteroidetes in feces	Week 4
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Calprotectin	Fecal calprotectin concentration	Week 0
Secondary	Calprotectin	Fecal calprotectin concentration	Week 4