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

June 26, 2017 updated by: University of California, Davis
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Locations

  • United States
    • California
      • Davis, California, United States, 95616
        • UC Davis

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

25 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Urine collected 12h previous to intervention and up to 24 h after intervention
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
Plasma collected before (0h) and up to 6h post intervention
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
Urine collected 12h previous to intervention and up to 24 h after intervention
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
Plasma collected before (0h) and up to 6h post intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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;
Before intervention (0h) and up to 24 h after intervention
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;
Before intervention (0h) and up to 24 h after intervention
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;
Before intervention (0h) and up to 24 h after intervention
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;
Before intervention (0h) and up to 24 h after intervention
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;
Before intervention (0h) and up to 24 h after intervention
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;
Before intervention (0h) and up to 24 h after intervention
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;
Before intervention (0h) and up to 24 h after intervention
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;
Before intervention (0h) and up to 24 h after intervention
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.
Before intervention (0h) and up to 24 h after intervention
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;
Before intervention (0h) and up to 24 h after intervention
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
Before intervention (0h) and up to 24 h after intervention

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, Davis

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Mars, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 25, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 25, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 19, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 26, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 28, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 28, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 26, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2017

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 429275

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Only researchers listed in the protocol and approved by the IRB will have access to IPD.

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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