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Intake-dependent Effect of Cocoa Flavanol Absorption, Metabolism and Excretion in Humans

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: NCT03201822
Recruitment Status : Completed
First Posted : June 28, 2017
Last Update Posted : June 28, 2017
Sponsor:
Collaborator:
Mars, Inc.
Information provided by (Responsible Party):
University of California, Davis

Brief Summary:
A randomized, double-masked and cross-over dietary intervention study in healthy young adult males to evaluate the concentration of F-derived metabolites in plasma and urine after single acute intakes of F-containing drinks on four different test days.

Condition or disease Intervention/treatment Phase
Healthy Other: 100 mg of Cocoa Flavanols/70 kg BW Other: 200 mg of Cocoa Flavanols/70 kg BW Other: 400 mg of Cocoa Flavanols/70 kg BW Other: 1000 mg of Cocoa Flavanols/70 kg BW Not Applicable

Detailed Description:
Flavanols (F) are plant-derived compounds commonly present in the human diet. Examples of F-containing foods and beverages are apples, chocolate, tea, wine, berries, pomegranate and nuts. The consumption of F-containing foods and beverages has been associated with improvements in cardiovascular health. In this context, there exists a great interest in describing the absorption, metabolism and excretion of F in humans, as it is thought that F-derived metabolites present in circulation are the mediators of F-beneficial effects in humans. Recently, we described a series of F-derived metabolites in circulation that are present after the consumption of a single acute intake amount of F in humans. A key question, however, is if the metabolites we observed after a single acute feeding are the same as those that occur in individuals who consume F-rich diets on a regular basis. Studies investigating the metabolism of numerous other xenobiotics have shown that the profile of metabolites can greatly vary over time, as well as with the amount of xenobiotic ingested. In this context, and considering that i) the amount of F-consumed from diet greatly varies among individuals, ii) recent epidemiology studies indicate that the vascular protective effects of F diets primarily occur when daily intake of F are relatively high; and iii) there is evidence of an intake amount-dependency on the vascular effects of F in dietary intervention studies; we submit it is important to assess whether or not there are F intake amount-dependent effects on the levels and profile of F-derived metabolites in humans. This study will provide new information concerning the F-derived metabolites that may be responsible for mediating F-beneficial effects in humans. We suggest the information that will be obtained from the outlined work will be particularly timely given ongoing discussion concerning the possible generation of dietary recommendations for F-rich foods.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Randomized, double-masked and cross-over dietary intervention study in healthy young adult males
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Intake-dependent Effect of Cocoa Flavanol Absorption, Metabolism and Excretion in Humans
Actual Study Start Date : April 1, 2013
Actual Primary Completion Date : May 25, 2013
Actual Study Completion Date : May 25, 2013

Arm Intervention/treatment
Experimental: 100 mg of Cocoa Flavanols/70 kg BW
Fruit flavored non-dairy drink containing 100 cocoa flavanol/70 kg BW
Other: 100 mg of Cocoa Flavanols/70 kg BW
Fruit-flavored non-dairy drink containing 100 cocoa flavanols/70kg BW.

Experimental: 200 mg of Cocoa Flavanols/70 kg BW
Fruit flavored non-dairy drink containing 200 cocoa flavanol/70 kg BW
Other: 200 mg of Cocoa Flavanols/70 kg BW
Fruit-flavored non-dairy drink containing 200 cocoa flavanols/70kg BW.

Experimental: 400 mg of Cocoa Flavanols/70 kg BW
Fruit flavored non-dairy drink containing 400 cocoa flavanol/70 kg BW
Other: 400 mg of Cocoa Flavanols/70 kg BW
Fruit-flavored non-dairy drink containing 400 cocoa flavanols/70kg BW.

Experimental: 1000 mg of Cocoa Flavanols/70 kg BW
Fruit flavored non-dairy drink containing 1000 cocoa flavanol/70 kg BW
Other: 1000 mg of Cocoa Flavanols/70 kg BW
Fruit-flavored non-dairy drink containing 1000 cocoa flavanols/70kg BW.




Primary Outcome Measures :
  1. Change in levels of gut microbiome derived metabolites in urine [ Time Frame: Urine collected 12h previous to intervention and up to 24 h after intervention ]
    Gut microbiome derived metabolites include conjugates of 5-(3',4'-dihydroxyphenyl)-g-valerolatone metabolites

  2. Change in levels of gut microbiome derived metabolites in plasma [ Time Frame: Plasma collected before (0h) and up to 6h post intervention ]
    Gut microbiome derived metabolites include conjugates of 5-(3',4'-dihydroxyphenyl)-g-valerolatone

  3. Change in levels of structurally related epicatechin metabolites in urine [ Time Frame: Urine collected 12h previous to intervention and up to 24 h after intervention ]
    Structurally related epicatechin metabolites include sulfated, glucuronidated and/or methylated metabolites of epicatechin

  4. Change in levels of structurally related epicatechin metabolites in plasma [ Time Frame: Plasma collected before (0h) and up to 6h post intervention ]
    Structurally related epicatechin metabolites include sulfated, glucuronidated and/or methylated metabolites of epicatechin


Secondary Outcome Measures :
  1. Composite of pharmacokinetic (PK) parameters of metabolites Maximum Plasma Concentration (CMax) [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    PK parameters: Cmax: maximum observed concentration in plasma;

  2. Composite of pharmacokinetic (PK) parameters of metabolites Time to Maximum Plasma Concentration [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    tmax: time to maximum concentration in plasma;

  3. Composite of pharmacokinetic (PK) parameters of metabolites Area Under the Curve [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    AUC0-t: area under the plasma concentration-time curve from hour 0 to the last measurable concentration in plasma;

  4. Composite of pharmacokinetic (PK) parameters of metabolites Area Under the Curve extrapolated to infinity [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    AUC0-∞: area under the plasma concentration-time curve extrapolated to infinity;

  5. Composite of pharmacokinetic (PK) parameters of metabolites Elimination Rate Constant [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    λZ: apparent terminal elimination rate constant in plasma;

  6. Composite of pharmacokinetic (PK) parameters of metabolites Elimination Half-Life [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    t1/2: apparent terminal elimination half-life in plasma;

  7. Composite of pharmacokinetic (PK) parameters of metabolites Systemic Clearance [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    CL/F: systemic clearance;

  8. Composite of pharmacokinetic (PK) parameters of metabolites Renal Clearance [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    CLR: renal clearance;sampling interval and the total interval examined;

  9. Composite of pharmacokinetic (PK) parameters of metabolites cumulative Amount Excreted in Feces [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    Aef(0-t): Cumulative amount excreted in the feces over each sampling interval and the total interval examined.

  10. Composite of pharmacokinetic (PK) parameters of metabolites Volume of Distribution [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    Vd/F: apparent volume of distribution;

  11. Composite of pharmacokinetic (PK) parameters of metabolites cumulative Amount Excreted in Urine [ Time Frame: Before intervention (0h) and up to 24 h after intervention ]
    Aeu(0-t): cumulative amount excreted in the urine over each



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • No prescription medications
  • BMI 18.5 - 29.9 kg/m2
  • Weight ≥ 110 pounds
  • previously consumed cocoa and peanut products, with no adverse reactions

Exclusion Criteria:

  • Adults unable to consent
  • Prisoners
  • Non-English speaking*
  • BMI ≥ 30 kg/m2
  • Allergies to nuts, cocoa and chocolate products
  • Active avoidance of coffee and caffeinated soft drinks
  • Under current medical supervision
  • A history of cardiovascular disease, stroke, renal, hepatic, or thyroid disease
  • History of clinically significant depression, anxiety or other psychiatric condition
  • History of Raynaud's disease
  • History of difficult blood draws
  • Indications of substance or alcohol abuse within the last 3 years
  • Current use of herbal, plant or botanical supplements (multi-vitamin/mineral supplements are allowed)
  • Blood Pressure > 140/90 mm Hg
  • GI tract disorders, previous GI surgery (except appendectomy)
  • Self-reported malabsorption (e.g. difficulty digesting or absorbing nutrients from food, potentially leading to bloating, cramping or gas)
  • Diarrhea within the last month, or antibiotic intake within the last month
  • Vegetarian, Vegan, food faddists, individuals using non-traditional diets, on a weight loss diet or individual following diets with significant deviations from the average diet
  • Metabolic panel results or complete blood counts that are outside of the normal reference range and are considered clinically relevant by the study physician
  • Screening LDL ≥ 190 mg/dl for those who have 0-1 major risk factors apart from LDL cholesterol (i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL)
  • Screening LDL ≥ 160 mg/dl for those who have 2 major risk factors apart from LDL cholesterol (i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL).

(using NCEP calculator http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof)

  • Screening LDL ≥ 130 mg/dl for those who have 2 major risk factors apart from LDL cholesterol (i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL), and a Framingham 10-year Risk Score 10-20% (Framingham risk calculated using NCEP calculator http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof)
  • Cold, flu, or upper respiratory condition at screening
  • Currently participating in a clinical or dietary intervention study

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): NCT03201822


Locations
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United States, California
UC Davis
Davis, California, United States, 95616
Sponsors and Collaborators
University of California, Davis
Mars, Inc.
Investigators
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Principal Investigator: Carl L Keen, PhD UC Davis
Study Director: Javier I Ottaviani, PhD Mars, Inc.
Publications:
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Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT03201822    
Other Study ID Numbers: 429275
First Posted: June 28, 2017    Key Record Dates
Last Update Posted: June 28, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Only researchers listed in the protocol and approved by the IRB will have access to IPD.

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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 University of California, Davis:
flavanol
ADME
cocoa flavanols
polyphenols