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| Name | Class |
|---|---|
| USDA Beltsville Human Nutrition Research Center | FED |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mixed Berries | Active Comparator | Strawberry and red raspberry composite served as a frozen drink |
|
| FOS | Active Comparator | Non-polyphenol, carbohydrate-based fermentable fiber/pre-biotic served as a frozen drink |
|
| Combination | Active Comparator | Mixed berry composite + FOS served as a frozen drink |
|
| Control | Placebo Comparator | Placebo similar in color to mixed berry supplement without any polyphenols served as a frozen drink |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mixed berries | Dietary Supplement | Strawberry and red raspberry |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in plasma biomarkers and measures of inflammation concentration: Nrf2/ NF-κB -response between 4 treatments | 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 | 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 | Analysis of GLP-2 will be done in plasma samples before and after chronic exposure to the study foods. | Baseline to 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in gut inflammatory markers between 4 treatments. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Characterize metabolite profiles (phenolic acids and urolithin derivatives) in urine and plasma. | 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 |
Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Amandeep Sandhu, Ph.D | Institue for Food Safety and Health/Illinois Insititute of Technology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Nutrition Research Center | Chicago | Illinois | 60616 | United States |
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| ID | Term |
|---|---|
| D050177 | Overweight |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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| FOS |
| Dietary Supplement |
Fructo-oligosaccharide |
|
| Control | Dietary Supplement | Placebo similar in color to mixed berry supplement without any polyphenols |
|
| Combination | Dietary Supplement | Mixed berry composite + FOS |
|
Bile acids in plasma and fecal samples will be determined using UHPLC-QQQ-MS. |
| Baseline to 4 weeks |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |