Clinical trial NCT03973996: Gut-level Antiinflammatory Activities of Green Tea in Metabolic Syndrome
Official title: Gut-level Antiinflammatory Activities of Green Tea in Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dysbiosis
Endotoxemia
Metabolic Syndrome
Inflammation
Keywords: Green tea
Gut barrier function
Gut dysbiosis
Inflammation
Metabolic endotoxemia
Metabolic syndrome
Microbiome
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: United States Department of Agriculture (USDA)
First posted: 2019-06-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: This study evaluates dietary green tea extract to improve gut health and inflammation in persons with metabolic syndrome and healthy adults. Participants will complete two phases of intervention in random order in which they will consume green tea extract or placebo for one month and then switch to the opposite treatment for an additional month.

Detailed description: Tea is the most abundantly consumed prepared beverage in the world. Green tea, containing catechins, exerts antiinflammatory activities. However, a fundamental gap exists concerning its intestinal-level targets that can prevent metabolic syndrome (MetS) development and progression. Studies in obese rodents indicate that green tea inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activation by limiting gut-derived endotoxin translocation to the portal circulation and decreasing hepatic Toll-like receptor-4 (TLR4) pro-inflammatory signaling. The objective of this clinical investigation is to establish evidence-based recommendations for green tea, based on improvements in endotoxemia and restored gut barrier function, that promote optimal health. The hypothesis is that green tea catechins function to limit metabolic endotoxemia by ameliorating gut dysbiosis-mediated inflammation that otherwise provokes intestinal permeability. This will be tested by conducting a double-blind, placebo-controlled, randomized-order, crossover trial in MetS and healthy persons to examine the efficacy of green tea on metabolic endotoxemia. Each treatment will be one-month in duration and separated by a washout period. The anticipated outcomes are expected to be of significance, because they will advance a dietary strategy to help avert MetS complications attributed to metabolic endotoxemia by establishing antiinflammatory prebiotic and antimicrobial bioactivities of catechins that promote intestinal health.

Eligibility criteria: Inclusion criteria:

Individuals with ≥3 of the following established criteria for metabolic syndrome:

* Fasting glucose 100-126 mg/dL
* Waist circumference \>89/\>102 cm for females/males
* HDL-C \<50/\<40 mg/dL for females/males
* Triglyceride \>150 mg/dL
* Blood pressure \>130/85 mmHg

Healthy adults:

* Body weight 19-25 kg/m2
* Fasting glucose \<100 mg/dL
* HDL-C \>50/\>40 mg/dL for females/males
* Triglyceride \<150 mg/dL
* Blood pressure \<120/80 mmHg

Exclusion criteria:

* Concurrent tea consumption
* Use of dietary supplements, prebiotics, or probiotics
* Use of antibiotics or antiinflammatory agents
* History of liver disease, cardiovascular disease, hypertension (blood pressure \>140/90 mmHg), or cancer
* History of gastrointestinal disorders, chronic diarrhea, or surgeries
* Hemochromatosis
* Parkinson's disease
* Use of medications to manage diabetes, hypertension, or hyperlipidemia
* Use of antipsychotic medications \[Clozapine, lithium, Diazepam\]
* Use of blood thinning medications \[Warfarin\]
* Use of high blood pressure medications \[nadolol\]
* Use of monoamine oxidase inhibitors \[selegiline\]
* Alcohol consumption \>2 drinks/d
* Smoking tobacco
* Vegetarian
* Pregnancy, lactation, or recent changes in birth control use for women

Primary outcomes:
measure: Change in metabolic endotoxemia
timeFrame: Day 0, 14, and 28 of the 28-day intervention
Secondary outcomes:
measure: Gastrointestinal permeability
timeFrame: Day 28 of the 28-day intervention
measure: Plasma inflammatory biomarker: C-reactive protein
timeFrame: Day 28 of the 28-day intervention
measure: Plasma inflammatory biomarkers: interleukin-6, interleukin-8, and tumor necrosis factor alpha
timeFrame: Day 28 of the 28-day intervention
measure: Plasma inflammatory biomarker: myeloperoxidase
timeFrame: Day 28 of the 28-day intervention
measure: Pro-inflammatory gene expression from peripheral blood mononuclear cells
timeFrame: Day 28 of the 28-day intervention
measure: Intestinal inflammatory biomarker: calprotectin
timeFrame: Days 25-27 of the 28-day intervention
measure: Intestinal inflammatory biomarker: myeloperoxidase
timeFrame: Days 25-27 of the 28-day intervention
measure: Changes in plasma catechins and their metabolites
timeFrame: Day 0, 14, and 28 of the 28-day intervention
measure: Fecal catechins and their metabolites
timeFrame: Days 25-27 of the 28-day intervention
measure: Fecal short-chain fatty acids
timeFrame: Days 25-27 of the 28-day intervention
measure: Gut microbiota diversity indices
timeFrame: Days 25-27 of the 28-day intervention
measure: Gut microbiota Firmicutes/Bacteroidetes ratio
timeFrame: Days 25-27 of the 28-day intervention
measure: Gut microbiota relative abundance
timeFrame: Days 25-27 of the 28-day intervention
measure: Gut microbiota function proportions
timeFrame: Days 25-27 of the 28-day intervention
measure: Change in plasma glucose
timeFrame: Day 0, 14, and 28 of the 28-day intervention
measure: Change in plasma insulin
timeFrame: Day 0, 14, and 28 of the 28-day intervention
measure: Change in plasma lipids
timeFrame: Day 0, 14, and 28 of the 28-day intervention
measure: Changes in serum alanine transaminase and aspartate transaminase
timeFrame: Day 0, 14, and 28 of the 28-day intervention
measure: Changes in serum creatinine and blood urea nitrogen
timeFrame: Day 0, 14, and 28 of the 28-day intervention
measure: Change in blood hematocrit
timeFrame: Day 0, 14, and 28 of the 28-day intervention
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Richard S Bruno, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dey P, Sasaki GY, Wei P, Li J, Wang L, Zhu J, McTigue D, Yu Z, Bruno RS. Green tea extract prevents obesity in male mice by alleviating gut dysbiosis in association with improved intestinal barrier function that limits endotoxin translocation and adipose inflammation. J Nutr Biochem. 2019 May;67:78-89. doi: 10.1016/j.jnutbio.2019.01.017. Epub 2019 Feb 8.
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.