Berries, Inflammation, and Gut Microbiome

Polyphenols and Human Gut Microbiome Interactions: Role of in Ameliorating Inflammation

The primary objectives are to characterize changes in indices of systemic and gut inflammation, assess host- and microbial-derived metabolite pools, and describe and link functional metagenomics and metatranscriptomic alterations in the gut microbiome with metabolite and inflammatory outcomes after acute (24hr) and chronic (4 week) intake of anthocyanins and ellagitannins from strawberry and red raspberries compared to a control diet (negative control), FOS (positive control, non-polyphenol, carbohydrate-based fermentable fiber/pre-biotic), or combination diet (berry composite + FOS) in human participants with low-grade inflammation.

Study Overview

Detailed Description

The proposed study will be conducted in humans according to Good Clinical Practice (GCP) guidelines. All subjects will review and sign an Informed Consent Form approved by the Illinois Institute of Technology's Institutional Review Boards (IRB) prior to screening.

This is a single-center, randomized, single-blinded, 4-arm, placebo-controlled clinical trial. It features an acute single exposure 24-h protocol and a chronic 4-week daily intake protocol to evaluate the effects of anthocyanins and ellagitannins from strawberry and red raspberry intake compared to a control diet, FOS, or FOS and berries combined on gut inflammation, in adults with chronic low-grade inflammation.

A planned sample size of 88 will be enrolled in the study. This study will require one initial screening visit, a pre-study visit, and 5 study visits. This study will take 5 weeks per subject to complete.

The initial screening visit will provide subject with their site-specific, IRB-approved informed consent document prior to the start of any study-related procedures. Subject eligibility will be determined through a high sensitivity C-Reactive Protein (hs-CRP) marker value, anthropometric measurements, vital signs, fasting blood glucose test (finger prick), and completion of a survey related to general eating, health, mood and exercise habits.

Eligible subjects will follow a limited polyphenolic diet throughout the duration of their participation, although stricter guidelines will be imposed during the 3 days prior to a study visit that involved blood/urine/fecal collection. Shopping lists and meal plans will be provided to subjects, along with counseling by the investigator's study investigators, to help subjects adhere to the limited polyphenolic diet. The trial will initiate with a 3-day food diary to assess background (pre-study) dietary intake followed by counseling to follow a diet relatively low in (poly)phenolic rich-beverages/foods, which will be maintained for the duration of the experiment. After an initial 7-day wash-in period on the limited polyphenolic diet, subjects will be randomized to 1 of 4 treatment sequences in the form of a drink: a mixed berries diet (raspberries and strawberries), a FOS diet (non-polyphenol, carbohydrate-based fermentable fiber/pre-biotic), a combination diet (mixed berries + FOS), or a control diet (negative control). Subjects will receive the same treatment for the duration of the study. Treatment codes will be maintained by the principal investigator.

Each visit will last ~2 hours and subjects will be required to remain at the Clinical Nutrition Research Center for the duration of the visit. Fasting blood samples will be collected at the 0 and 24h time points via a butterfly needle placed by a certified phlebotomist.

Study Type

Interventional

Enrollment (Actual)

105

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 Contact

Study Locations

    • Illinois
      • Chicago, Illinois, United States, 60616
        • Clinical Nutrition Research Center

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

20 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria

  • C-Reactive Protein (hs-CRP) > 1.0 and ≤ 10 ng/L
  • BMI ≥ 25 kg/m2
  • Aged 20-60 years
  • Able to provide informed consent and comply with study procedures
  • Willing to maintain stable body weight and follow his/her habitual diet and physical activity patterns throughout the trial.
  • Judged by the Investigator to be in general good health on the basis of medical history and screening laboratory tests.
  • People with no documented disease condition that would interfere with the study endpoints (ie., CVD, diabetes, hypertension, major organ diseases) or taking medication or dietary supplements that may interfere with study endpoints

Exclusion Criteria

  • Current smoker or marijuana user
  • No history or presence of atherosclerosis/cardiovascular disease, inflammatory disease, diabetes mellitus, or other systemic diseases, psychological or psychiatric disorders that may interfere with study outcomes.
  • Taking any medications and/or supplements that would interfere with outcomes of the study (i.e., lipid-lowering medications, anti-inflammatory drugs, etc)
  • Take part in prebiotics, probiotics or drugs active on gastrointestinal motility or a laxative of any class within 1 month
  • Unstable use of any medication/supplement, this could include marijuana used as -needed for medical reasons
  • Have a history of cancer, except for non-melanoma skin cancer in past 5 years
  • Addicted to drugs and/or alcohol (>4 drinks/day)
  • Have been exposed to any non-registered drug product within last 30 days.
  • Working overnight (e.g. 3rd shift of overnight workers)
  • Excessive exercisers or trained athletes
  • Have allergies/intolerances to any of the study products.
  • Extreme dietary habits (ie. vegetarian/vegan)
  • Excessive coffee/tea drinker (>4 cups/day)
  • Actively losing weight/ trying to lose weight (unstable body weight fluctuations of > 5 kg in 3 months)
  • Donated blood within last 3 months
  • Participated in a clinical trial within 1 month
  • Female who is pregnant, planning to be pregnant, breastfeeding
  • Any condition the Investigator believes would interfere with his or her ability to provide informed consent or comply with the study protocol, or which might confound

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: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Mixed Berries
Strawberry and red raspberry composite served as a frozen drink
Strawberry and red raspberry
Active Comparator: FOS
Non-polyphenol, carbohydrate-based fermentable fiber/pre-biotic served as a frozen drink
Fructo-oligosaccharide
Active Comparator: Combination
Mixed berry composite + FOS served as a frozen drink
Mixed berry composite + FOS
Placebo Comparator: Control
Placebo similar in color to mixed berry supplement without any polyphenols served as a frozen drink
Placebo similar in color to mixed berry supplement without any polyphenols

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in plasma biomarkers and measures of inflammation concentration: Nrf2/ NF-κB -response between 4 treatments
Time Frame: Baseline to 4 weeks
Plasma biomarkers and measures of inflammation: Nrf2/ NF-κB activation in monocytes will be analyzed.
Baseline to 4 weeks
Changes in plasma biomarkers and measures of inflammation concentration-response between 4 treatments
Time Frame: Baseline to 4 weeks
Inflammatory cytokines (Interleukin-6 (IL-6), High Sensitivity C-Reactive Protein (hs-CRP), Tumor Necrosis Factor-α (TNF-α)) will be measured.
Baseline to 4 weeks
Changes in plasma biomarkers and measures of inflammation concentration (GLP-2)-response between 4 treatments
Time Frame: Baseline to 4 weeks
Analysis of GLP-2 will be done in plasma samples before and after chronic exposure to the study foods.
Baseline to 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in gut inflammatory markers between 4 treatments.
Time Frame: Baseline to 4 weeks
The concentration of calprotectin, zonulin, and IgA in fecal samples will be determined by enzyme-linked immunosorbent assay (ELISA) before and after chronic exposure to study foods.
Baseline to 4 weeks
Changes in Bile acids between 4 treatments.
Time Frame: Baseline to 4 weeks
Bile acids in plasma and fecal samples will be determined using UHPLC-QQQ-MS.
Baseline to 4 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterize metabolite profiles (phenolic acids and urolithin derivatives) in urine and plasma.
Time Frame: Baseline to 4 weeks
Polyphenolic metabolites (anthocyanin, ellagitannins and other phenolic components) will be identified and quantified in urine and plasma.Metabolites in samples will be identified and quantified using an Agilent 6550 iFunnel UHPLC-QTOF-MS and 6460 UHPLC-QQQ-MS, respectively.
Baseline to 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Amandeep Sandhu, Ph.D, Institue for Food Safety and Health/Illinois Insititute of Technology

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)

October 7, 2019

Primary Completion (Actual)

March 31, 2023

Study Completion (Estimated)

February 1, 2024

Study Registration Dates

First Submitted

September 18, 2019

First Submitted That Met QC Criteria

September 19, 2019

First Posted (Actual)

September 24, 2019

Study Record Updates

Last Update Posted (Estimated)

December 18, 2023

Last Update Submitted That Met QC Criteria

December 15, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

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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