Clinical trial NCT03413735: Dietary Green Tea Confection For Resolving Gut Permeability-Induced Metabolic Endotoxemia In Obese Adults
Official title: Dietary Green Tea Confection For Resolving Gut Permeability-Induced Metabolic Endotoxemia In Obese Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Endotoxemia
Inflammation
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2018-01-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Endotoxin
timeFrame: Week 0 - Fasting
measure: Endotoxin
timeFrame: Week 2 - Fasting
measure: Endotoxin
timeFrame: Week 4 - Fasting
Secondary outcomes:
measure: Gut Permeability - Lactulose to Mannitol Ratio
timeFrame: Week 0 - 0-5 hours
measure: Gut Permeability - Lactulose to Mannitol Ratio
timeFrame: Week 0 - 6-24 hours
measure: Gut Permeability - Lactulose to Mannitol Ratio
timeFrame: Week 4 - 0-5 hours
measure: Gut Permeability - Lactulose to Mannitol Ratio
timeFrame: Week 4 - 6-24 hours
measure: Gut Permeability - Sucralose to Erythritol Ratio
timeFrame: Week 0 - 6-24 hours
measure: Gut Permeability - Sucralose to Erythritol Ratio
timeFrame: Week 0 - 0-24 hours
measure: Urinary Sucralose/Erythritol Ratio (mg/mg)
timeFrame: Week 4 - 6-24 hours
measure: Gut Permeability - Sucralose to Erythritol Ratio
timeFrame: Week 4 - 0-24 hours
measure: Firmicutes to Bacteroidetes Ratio - Microbiota
timeFrame: Week 0
measure: Firmicutes to Bacteroidetes Ratio - Microbiota
timeFrame: Week 4
measure: Bioavailability - Epigallocatechin Gallate
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of a green tea confection
measure: Bioavailability - Epigallocatechin
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of a green tea confection
measure: Bioavailability - Epicatechin Gallate
timeFrame: Prior to the intervention enrollment...0-12 hours post-ingestion of a green tea confection
measure: Bioavailability - Epicatechin
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of a green tea confection
measure: Cmax of Epigallocatechin Gallate
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection
measure: Cmax of Epigallocatechin
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection
measure: Cmax of Epicatechin Gallate
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection
measure: Cmax of Epicatechin
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection
measure: Tmax of Epigallocatechin Gallate
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection
measure: Tmax of Epigallocatechin
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection
measure: Tmax of Epicatechin Gallate
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection
measure: Tmax of Epicatechin
timeFrame: Prior to intervention enrollment...0-12 hours post-ingestion of green tea confection
measure: Calprotectin
timeFrame: Week 0
measure: Calprotectin
timeFrame: Week 4
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Richard Bruno, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.