Clinical trial NCT04100200: Berries, Inflammation, and Gut Microbiome
Official title: Polyphenols and Human Gut Microbiome Interactions: Role of in Ameliorating Inflammation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Overweight or Obesity
Healthy
Keywords: Strawberry
Raspberry
Metabolic responses
Gut microbiome
Inflammatory markers
Lead sponsor: Clinical Nutrition Research Center, Illinois Institute of Technology
Sponsor class: INDUSTRY
Collaborators: name: USDA Beltsville Human Nutrition Research Center
First posted: 2019-09-24
Enrollment: 105
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in plasma biomarkers and measures of inflammation concentration: Nrf2/ NF-κB -response between 4 treatments
timeFrame: Baseline to 4 weeks
measure: Changes in plasma biomarkers and measures of inflammation concentration-response between 4 treatments
timeFrame: Baseline to 4 weeks
measure: Changes in plasma biomarkers and measures of inflammation concentration (GLP-2)-response between 4 treatments
timeFrame: Baseline to 4 weeks
Secondary outcomes:
measure: Changes in gut inflammatory markers between 4 treatments.
timeFrame: Baseline to 4 weeks
measure: Changes in Bile acids between 4 treatments.
timeFrame: Baseline to 4 weeks
Other outcomes:
measure: Characterize metabolite profiles (phenolic acids and urolithin derivatives) in urine and plasma.
timeFrame: Baseline to 4 weeks
Locations:
city: Chicago
country: United States
facility: Clinical Nutrition Research Center
state: Illinois
Study officials:
affiliation: Institue for Food Safety and Health/Illinois Insititute of Technology
name: Amandeep Sandhu, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: