Gut-level Antiinflammatory Activities of Green Tea in Metabolic Syndrome

Metabolic Syndrome Clinical Trial

Official title:

Gut-level Antiinflammatory Activities of Green Tea in Metabolic Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03973996
• Other study ID #: 2018H0592
• Status: Completed
• Phase: N/A
• Start date: July 1, 2019
• Est. completion date: March 1, 2021

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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 1, 2021
• Est. primary completion date: March 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Dysbiosis
• Endotoxemia
• Inflammation
• Metabolic Syndrome
• Syndrome

Intervention

Dietary Supplement:
• Green Tea Extract
A gummy confection with catechin-rich green tea extract (1 g/d)
• Placebo
A matched gummy confection formulated without green tea extract

Locations

Country	Name	City	State
United States	The Ohio State University	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Ohio State University	USDA Beltsville Human Nutrition Research Center

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — 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	Change in metabolic endotoxemia	Serum endotoxin concentration (EU/mL) will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.	Day 0, 14, and 28 of the 28-day intervention
Secondary	Gastrointestinal permeability	Lactulose/mannitol ratio will be measured in urine collected 0-5 h post-ingestion to assess small intestinal permeability. Sucralose (%) will be measured in urine collected 0-24 h post-ingestion to assess colonic permeability. Between-treatment differences will be measured in MetS vs. healthy individuals.	Day 28 of the 28-day intervention
Secondary	Plasma inflammatory biomarker: C-reactive protein	Plasma concentration (mg/L) of C-reactive protein will be measured at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.	Day 28 of the 28-day intervention
Secondary	Plasma inflammatory biomarkers: interleukin-6, interleukin-8, and tumor necrosis factor alpha	Plasma concentrations (pg/mL) of interleukin-6, interleukin-8, and tumor necrosis factor alpha will be measured individually at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.	Day 28 of the 28-day intervention
Secondary	Plasma inflammatory biomarker: myeloperoxidase	Plasma concentration (ng/mL) of myeloperoxidase will be measured at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.	Day 28 of the 28-day intervention
Secondary	Pro-inflammatory gene expression from peripheral blood mononuclear cells	Relative expression of toll-like receptor 4, myeloid differentiation factor 88, p65 subunit of NF-kappa B, interleukin-6, interleukin-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1 will be measured individually at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.	Day 28 of the 28-day intervention
Secondary	Intestinal inflammatory biomarker: calprotectin	Fecal concentration (µg/g) of calprotectin will be measured in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.	Days 25-27 of the 28-day intervention
Secondary	Intestinal inflammatory biomarker: myeloperoxidase	Fecal concentration (ng/g) of myeloperoxidase will be measured in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.	Days 25-27 of the 28-day intervention
Secondary	Changes in plasma catechins and their metabolites	Plasma concentrations (nmol/L) of epigallocatechin gallate, epicatechin gallate, epigallocatechin, epicatechin, gamma-valerolactones, and catechin-derivates will be measured individually at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.	Day 0, 14, and 28 of the 28-day intervention
Secondary	Fecal catechins and their metabolites	Fecal concentrations (µmol/kg) of epigallocatechin gallate, epicatechin gallate, epigallocatechin, epicatechin, gamma-valerolactones, and catechin-derivates will be measured individually in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.	Days 25-27 of the 28-day intervention
Secondary	Fecal short-chain fatty acids	Fecal concentrations (mmol/kg) of butyrate, acetate, propionate, isobutyric acid, and isovaleric acid will be measured individually in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.	Days 25-27 of the 28-day intervention
Secondary	Gut microbiota diversity indices	Gut microbiota diversity indices (Shannon species and Chao1) will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.	Days 25-27 of the 28-day intervention
Secondary	Gut microbiota Firmicutes/Bacteroidetes ratio	Gut microbiota Firmicutes/Bacteroidetes ratio will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.	Days 25-27 of the 28-day intervention
Secondary	Gut microbiota relative abundance	Gut microbiota relative abundance (% order, genus, and species level) will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.	Days 25-27 of the 28-day intervention
Secondary	Gut microbiota function proportions	Gut microbiota function proportions (%) based on microbial genome analysis will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.	Days 25-27 of the 28-day intervention
Secondary	Change in plasma glucose	Plasma concentration (mg/dL) of glucose will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.	Day 0, 14, and 28 of the 28-day intervention
Secondary	Change in plasma insulin	Plasma concentration (µIU/mL) of insulin will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.	Day 0, 14, and 28 of the 28-day intervention
Secondary	Change in plasma lipids	Plasma concentrations (mg/dL) of triglyceride and HDL-cholesterol will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.	Day 0, 14, and 28 of the 28-day intervention
Secondary	Changes in serum alanine transaminase and aspartate transaminase	Serum concentrations (U/L) of alanine transaminase and aspartate transaminase will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.	Day 0, 14, and 28 of the 28-day intervention
Secondary	Changes in serum creatinine and blood urea nitrogen	Serum concentrations (U/L) of creatinine and blood urea nitrogen will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.	Day 0, 14, and 28 of the 28-day intervention
Secondary	Change in blood hematocrit	Blood hematocrit (%) will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.	Day 0, 14, and 28 of the 28-day intervention