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Gut-level Antiinflammatory Activities of Green Tea in Metabolic Syndrome

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ClinicalTrials.gov Identifier: NCT03973996
Recruitment Status : Recruiting
First Posted : June 4, 2019
Last Update Posted : July 19, 2019
Sponsor:
Collaborator:
USDA Beltsville Human Nutrition Research Center
Information provided by (Responsible Party):
Richard Bruno, Ohio State University

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.

Condition or disease Intervention/treatment Phase
Dysbiosis Endotoxemia Metabolic Syndrome Inflammation Dietary Supplement: Green Tea Extract Dietary Supplement: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Gut-level Antiinflammatory Activities of Green Tea in Metabolic Syndrome
Actual Study Start Date : July 1, 2019
Estimated Primary Completion Date : October 31, 2020
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Green Tea
Participants consuming gummy confections with catechin-rich green tea extract daily for 4 weeks
Dietary Supplement: Green Tea Extract
A gummy confection with catechin-rich green tea extract (1 g/d)
Other Name: Camellia sinesis plant extract

Placebo Comparator: Placebo
Participants consuming matched gummy confections formulated without green tea extract daily for 4 weeks
Dietary Supplement: Placebo
A matched gummy confection formulated without green tea extract




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03973996


Contacts
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Contact: Richard S Bruno, PhD, RD 6142925522 bruno.27@osu.edu
Contact: Joanna K Hodges, PhD 6142924004 hodges.466@osu.edu

Locations
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United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Richard Bruno, PhD    614-292-4004    bruno.27@osu.edu   
Contact: Joanna Hodges, PhD    614-292-4004    hodges.466@osu.edu   
Principal Investigator: Richard Bruno, PhD         
Sub-Investigator: Joanna Hodges, PhD         
Sponsors and Collaborators
Ohio State University
USDA Beltsville Human Nutrition Research Center
Investigators
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Principal Investigator: Richard S Bruno, PhD, RD Ohio State University

Publications:
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Responsible Party: Richard Bruno, Principal Investigator, Ohio State University
ClinicalTrials.gov Identifier: NCT03973996     History of Changes
Other Study ID Numbers: 2018H0592
First Posted: June 4, 2019    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Richard Bruno, Ohio State University:
Green tea
Gut barrier function
Gut dysbiosis
Inflammation
Metabolic endotoxemia
Metabolic syndrome
Microbiome

Additional relevant MeSH terms:
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Syndrome
Inflammation
Metabolic Syndrome
Endotoxemia
Dysbiosis
Disease
Pathologic Processes
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Bacteremia
Sepsis
Infection
Toxemia
Systemic Inflammatory Response Syndrome
Anti-Inflammatory Agents