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Evaluating the Availability of Berry Phytonutrients Post-consumption of Fresh and Processed Blueberry by Healthy Adults (BAM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04175106
Recruitment Status : Suspended (COVID-2019)
First Posted : November 22, 2019
Last Update Posted : April 24, 2020
Sponsor:
Collaborator:
Foundation for Food and Agriculture Research
Information provided by (Responsible Party):
Colin D. Kay, North Carolina State University

Brief Summary:

This study will evaluate the availability of phytonutrients in two blueberry varieties, chosen for their phytonutrient levels. This will be compared to phytonutrient-matched processed protein bar and a macronutrient-matched control meal, in healthy human volunteers. Blueberry phytonutrients will be analyzed in blood and urine over a four-day period, 48h prior to consumption and 48h after. The participants will consume each of the four meals over a 3-month period (4-way crossover design, 4 blocks of 4-day periods). The main objective of this study is to compare the proportions of blueberry phytonutrients recovered in the blood and urine after ingestion of the four treatments. We hypothesize that phytonutrient content will be predictive of human bioavailability and that a berry-enriched processed product will have similar phytonutrient bioavailability to unprocessed berries.

The results of this study may establish if the nutritional value of a berry can be predicted or enhanced to provide elevated nutritional quality, with the ultimate goal of maximizing the health benefits of fruit consumption. As it is challenging for many to increase their fruit and vegetable intake to government recommended levels (5+ servings per day), the present proof-of-concept study explores a reasonable approach to help consumers achieve optimal health associated with high fruit and vegetable intakes, within the context of current consumption patterns, through enhancement of the nutritional density and bioavailability of common fruits and consumer products.


Condition or disease Intervention/treatment Phase
Healthy Other: a non-traditional (i.e., not typically available in the supermarket) blueberry cultivar bred using natural plant breeding techniques and established as having enhanced nutritive value Other: a standard commercially available blueberry variety (i.e., cultivar) Other: a "minimally processed" blueberry-rich protein bar Other: a control shake of matched-nutritive content Not Applicable

Detailed Description:

This study will evaluate the availability of phytonutrients in two blueberry varieties, chosen for their phytonutrient levels. This will be compared to phytonutrient-matched processed protein bar and a macronutrient-matched control meal, in healthy human volunteers. Blueberry phytonutrients will be analyzed in blood and urine over a four-day period, 48h prior to consumption and 48h after. The participants will consume each of the four meals over a 3-month period (4-way crossover design, 4 blocks of 4-day periods).

The main objective of this study is to compare the proportions of blueberry phytonutrients recovered in the blood and urine after ingestion of the four treatments.

After eligibility is confirmed, subjects will be randomly assigned to the four berry related interventions. The consumption of each intervention corresponds to one study period, which are separated by one-week washout. Blood will be collected at baseline and across 48h (1h, 3h, 6h, 9h, 24h, 48h) after intervention consumption while urine will be collected for 48h before and after intervention (-48h, -24h, 0-9h, 9-24h, 24-48h).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Establishing Optimal Nutritional Quality of Blueberries: a Proof of Concept Study to Improve the Nutritional Quality of the Average Diet Using Common Plant Breeding and Processing Practices.
Actual Study Start Date : December 13, 2019
Estimated Primary Completion Date : January 8, 2021
Estimated Study Completion Date : January 8, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: a phytochemical-rich blueberry variety
Single-time consumption of 150 g phytochemical-rich blueberry per participant.
Other: a non-traditional (i.e., not typically available in the supermarket) blueberry cultivar bred using natural plant breeding techniques and established as having enhanced nutritive value

150 g of a non-traditional (i.e., not typically available in the supermarket) blueberry cultivar bred using natural plant breeding techniques and established as having enhanced nutritive value.

Dietary restrictions will be observed (i.e. avoidance of food or supplements containing berry phytonutrients) for 7 days before each arm visit and throughout the study days.


Experimental: a phytochemical-poor blueberry variety
Single-time consumption of 150 g phytochemical-poor blueberry per participant.
Other: a standard commercially available blueberry variety (i.e., cultivar)

150 g of a standard commercially available blueberry variety (i.e., cultivar).

Dietary restrictions will be observed (i.e. avoidance of food or supplements containing berry phytonutrients) for 7 days before each arm visit and throughout the study days.


Experimental: a "minimally processed" blueberry-rich protein bar
Single-time consumption of blueberry-rich protein bar matched for 150 g blueberry phytochemicals.
Other: a "minimally processed" blueberry-rich protein bar

A "minimally processed" blueberry-rich protein bar matched to the phytonutrient content of the 150 g of the non-traditional blueberry.

Dietary restrictions will be observed (i.e. avoidance of food or supplements containing berry phytonutrients) for 7 days before each arm visit and throughout the study days.


Placebo Comparator: a blueberry control powder of matched-nutritive content
Single-time consumption of control beverage matched for the macronutrient content of the blueberry-rich protein bar.
Other: a control shake of matched-nutritive content

The matched nutritive content of the blueberry-rich protein bar will be dissolved in rice milk.

Dietary restrictions will be observed (i.e. avoidance of food or supplements containing berry phytonutrients) for 7 days before each arm visit and throughout the study days.





Primary Outcome Measures :
  1. Bioavailability of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis [ Time Frame: 4 days collection per intervention; 1 baseline collection, followed by 1,3,6,9,24 and 48 hours post-treatment collections or blood, and -48,-24,0-9, 9-24 and 24-48 hours collections for urine. ]
    Assessment of (poly)phenol bioavailability in the blood and urine after consumption of the treatments, using broad spectrum metabolomic analysis via UPLC-MS/MS (ultra-performance liquid chromatography coupled with tandem mass spectrometry).


Secondary Outcome Measures :
  1. Characterization of maximum serum concentration [Cmax] of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis [ Time Frame: 4 days collection per intervention; 1 baseline collection, followed by 1,3,6,9,24 and 48 hours post-treatment collections or blood, and -48,-24,0-9, 9-24 and 24-48 hours collections for urine. ]
    Characterization of differences in the Cmax of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis via UPLC-MS/MS.


Other Outcome Measures:
  1. Characterization of time at maximum concentration [Tmax] of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis [ Time Frame: 4 days collection per intervention; 1 baseline collection, followed by 1,3,6,9,24 and 48 hours post-treatment collections or blood, and -48,-24,0-9, 9-24 and 24-48 hours collections for urine. ]
    Characterization of differences in the Tmax of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis via UPLC-MS/MS.

  2. Characterization of the half-life [t1/2] of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis [ Time Frame: 4 days collection per intervention; 1 baseline collection, followed by 1,3,6,9,24 and 48 hours post-treatment collections or blood, and -48,-24,0-9, 9-24 and 24-48 hours collections for urine. ]
    Characterization of differences in the t1/2 of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis via UPLC-MS/MS.

  3. Characterization of the area under the curve [AUC] of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis [ Time Frame: 4 days collection per intervention; 1 baseline collection, followed by 1,3,6,9,24 and 48 hours post-treatment collections or blood, and -48,-24,0-9, 9-24 and 24-48 hours collections for urine. ]
    Characterization of differences in the AUC of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis via UPLC-MS/MS.

  4. Characterization of the area under the first moment curve [AUMC] of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis [ Time Frame: 4 days collection per intervention; 1 baseline collection, followed by 1,3,6,9,24 and 48 hours post-treatment collections or blood, and -48,-24,0-9, 9-24 and 24-48 hours collections for urine. ]
    Characterization of differences in the AUMC of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis via UPLC-MS/MS.

  5. Clearance (CL) of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis [ Time Frame: 4 days collection per intervention; 1 baseline collection, followed by 1,3,6,9,24 and 48 hours post-treatment collections or blood, and -48,-24,0-9, 9-24 and 24-48 hours collections for urine. ]
    Characterization of differences in the CL of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis via UPLC-MS/MS.

  6. Volume of distribution (Vd) of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis [ Time Frame: 4 days collection per intervention; 1 baseline collection, followed by 1,3,6,9,24 and 48 hours post-treatment collections or blood, and -48,-24,0-9, 9-24 and 24-48 hours collections for urine. ]
    Characterization of differences in the Vd of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis via UPLC-MS/MS.

  7. Mean residence time (MRT) of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis [ Time Frame: 4 days collection per intervention; 1 baseline collection, followed by 1,3,6,9,24 and 48 hours post-treatment collections or blood, and -48,-24,0-9, 9-24 and 24-48 hours collections for urine. ]
    Characterization of differences in the MRT of (poly)phenols and microbial metabolites in the blood and urine between the treatments, using broad spectrum metabolomic analysis via UPLC-MS/MS.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   30 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • male and female adults between 30-60 years;
  • non-smokers, non-tobacco users (no vaping nor deeping), or who ceased it ≥ 6 months ago;
  • who present no allergies to fruits or vegetables containing polyphenolic (e.g. anthocyanins, flavonoids) and phenolic acids such as blueberries, red apple, strawberry, red orange, purple onion and broccoli;
  • who present no allergies to dairy products, specifically whey protein, fructose or salicylates;
  • who are generally healthy and without chronic diseases including cancer, type 1 and 2 diabetes;
  • who are not prescribed thyroid or hypoglycemic medication or hormone replacement therapy (HRT) (due to the likely concomitant effects that these medications cause on the primary endpoint in the trial);
  • who has not been consuming any phytonutrient-containing supplements (e.g. with cocoa, coffee, berry, polyphenol, flavonoid, or anthocyanin extracts) for at least a month before the study and willing to not consume it during the study;
  • who lives within 40 miles from the North Carolina Research Campus (NCRC) campus;
  • those agreeing to restrict dietary intake of rich sources of phytonutrients targeted on the study during the wash-out and clinical sampling periods, agreeing to comply with a biological sampling protocol involving the collection of urine and blood samples, and to record their additional dietary intake over 2 days before each intervention, and two days after the intake of the intervention treatments;
  • who have BMI ≥18.5 and ≤ 30 (lbs/in2x703);
  • who have a successful (i.e., within normal range for healthy individuals) biochemical, hematological and urine analyses assessed by the clinical advisor as established during the screening period prior to final enrollment.

Exclusion Criteria:

  • current smokers (vaping and deeping included), or ex-smokers ceasing < 6 months before recruitment;
  • pregnant or breastfeeding;
  • subjects with existing or significant past medical history of vascular disease or medical conditions likely to affect the study measures i.e. vascular disease, circulatory (i.e. Reynaud's), diabetes, hepatic, renal, digestive, hematological, cancer, or thyroid disease;
  • fructose intolerant subjects or those with known allergy to salicylates, dairy products, specifically whey protein, or to berries;
  • those unprepared to adhere to dietary restrictions for 1 week preceding and during each intervention or unwilling to comply with the assessments per protocol;
  • who are in parallel participation in another research project involving dietary intervention and/or sampling of biological fluids/material;
  • those on therapeutic diets or having experienced substantial weight loss (to be judged by clinical advisor) within 3 months of screening;
  • those taking phytonutrient-containing supplements (e.g. with cocoa, coffee, berry, polyphenol, flavonoid, or anthocyanin extracts), unwilling to cease intake during, and 1 month preceding the trial, or unwilling to stop existing intake of other supplements or regular use of large-dose nutrient, herbal, and dietary supplements during the past one to two weeks, or planning to use them during the study;
  • prescribed thyroid, hypoglycemic medication or HRT medication -other medications will be assessed for suitability by the clinical advisor;
  • those having donated blood in the last month;
  • individuals that consume more than 1 and 2 drinks of alcohol per day for women and men, respectively, or more than 7 and 14 drinks per week for women and men, respectively (U.S. Department of Health and Human Services and U.S. Department of Agriculture Dietary guidelines 2015-2020);
  • currently on a weight-reducing plan or using weight-loss medications (e.g., selective serotonin reuptake inhibitors, steroids, Ritalin, appetite suppressants such as Diethylpropion or Amfepramone, and weight loss medications such as Alli, Xenical, Qsymia, Belviq, Contrave, and Saxenda), or planning to continue this treatment during the 10-week period of the study;
  • who has BMI<18.5 and >30 (lbs/in2x703);
  • who presents abnormal biochemical, hematological or urinary results, and measurements considered to be counter-indicative for the study, including: kidney and liver function, fasting glucose (especially if indicative of diabetes), lipid abnormalities, full blood count as established during the screening period prior to final enrollment.

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): NCT04175106


Locations
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United States, North Carolina
Plants for Human Health Institute, North Carolina State University
Kannapolis, North Carolina, United States, 28081
Sponsors and Collaborators
North Carolina State University
Foundation for Food and Agriculture Research
Investigators
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Principal Investigator: Colin D Kay, PhD North Carolina State University
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Responsible Party: Colin D. Kay, Associate Professor in Nutrition Science, PhD, North Carolina State University
ClinicalTrials.gov Identifier: NCT04175106    
Other Study ID Numbers: 19138
First Posted: November 22, 2019    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: April 2020

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