- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03973996
Gut-level Antiinflammatory Activities of Green Tea in Metabolic Syndrome
December 16, 2021 updated by: Richard Bruno, Ohio State University
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- The Ohio State University
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Green Tea
Participants consuming gummy confections with catechin-rich green tea extract daily for 4 weeks
|
A gummy confection with catechin-rich green tea extract (1 g/d)
Other Names:
|
Placebo Comparator: Placebo
Participants consuming matched gummy confections formulated without green tea extract daily for 4 weeks
|
A matched gummy confection formulated without green tea extract
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in metabolic endotoxemia
Time Frame: Day 0, 14, and 28 of the 28-day intervention
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Gastrointestinal permeability
Time Frame: Day 28 of the 28-day intervention
|
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
|
Plasma inflammatory biomarker: C-reactive protein
Time Frame: Day 28 of the 28-day intervention
|
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
|
Plasma inflammatory biomarkers: interleukin-6, interleukin-8, and tumor necrosis factor alpha
Time Frame: Day 28 of the 28-day intervention
|
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
|
Plasma inflammatory biomarker: myeloperoxidase
Time Frame: Day 28 of the 28-day intervention
|
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
|
Pro-inflammatory gene expression from peripheral blood mononuclear cells
Time Frame: Day 28 of the 28-day intervention
|
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
|
Intestinal inflammatory biomarker: calprotectin
Time Frame: Days 25-27 of the 28-day intervention
|
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
|
Intestinal inflammatory biomarker: myeloperoxidase
Time Frame: Days 25-27 of the 28-day intervention
|
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
|
Changes in plasma catechins and their metabolites
Time Frame: Day 0, 14, and 28 of the 28-day intervention
|
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
|
Fecal catechins and their metabolites
Time Frame: Days 25-27 of the 28-day intervention
|
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
|
Fecal short-chain fatty acids
Time Frame: Days 25-27 of the 28-day intervention
|
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
|
Gut microbiota diversity indices
Time Frame: Days 25-27 of the 28-day intervention
|
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
|
Gut microbiota Firmicutes/Bacteroidetes ratio
Time Frame: Days 25-27 of the 28-day intervention
|
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
|
Gut microbiota relative abundance
Time Frame: Days 25-27 of the 28-day intervention
|
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
|
Gut microbiota function proportions
Time Frame: Days 25-27 of the 28-day intervention
|
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
|
Change in plasma glucose
Time Frame: Day 0, 14, and 28 of the 28-day intervention
|
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
|
Change in plasma insulin
Time Frame: Day 0, 14, and 28 of the 28-day intervention
|
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
|
Change in plasma lipids
Time Frame: Day 0, 14, and 28 of the 28-day intervention
|
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
|
Changes in serum alanine transaminase and aspartate transaminase
Time Frame: Day 0, 14, and 28 of the 28-day intervention
|
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
|
Changes in serum creatinine and blood urea nitrogen
Time Frame: Day 0, 14, and 28 of the 28-day intervention
|
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
|
Change in blood hematocrit
Time Frame: Day 0, 14, and 28 of the 28-day intervention
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Richard S Bruno, PhD, RD, Ohio State University
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 1, 2019
Primary Completion (Actual)
March 1, 2021
Study Completion (Actual)
March 1, 2021
Study Registration Dates
First Submitted
May 30, 2019
First Submitted That Met QC Criteria
June 3, 2019
First Posted (Actual)
June 4, 2019
Study Record Updates
Last Update Posted (Actual)
December 17, 2021
Last Update Submitted That Met QC Criteria
December 16, 2021
Last Verified
December 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2018H0592
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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