Absorption, Metabolism, and Excretion of (-)-[2-14C]Epicatechin in Humans

NCT ID: NCT01969994

Last Updated: 2013-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2009-12-31

Brief Summary

The purpose of this study is to determine the absorption, metabolism and excretion of (-)-epicatechin using the radiolabeled tracer (-)-[2-14C]epicatechin in healthy male volunteers observing a flavanol-/procyanidin-controlled background diet.

Detailed Description

Flavanols and their oligomeric derivatives, the procyanidins, are plant-derived compounds commonly present in the human diet. Accumulating data demonstrate a causal role for dietary flavanols in mediating the cardiovascular benefits associated with the consumption of flavanol-/procyanidin-containing foods. In this context, there exists a great interest in understanding the absorption, distribution, metabolism and excretion (ADME) of flavanols in humans. While significant advances in understanding the ADME of flavanols were made, the data obtained thus far remain fairly preliminary and with significant shortfalls and seeming contradictions. Aimed at addressing the challenges and gaps of previous investigations, this study will investigate the ADME of (-)-epicatechin, one of the most abundant dietary flavanols, following the intake of radiolabeled (-)-[2-14C]epicatechin by healthy humans observing a flavanol-/procyanidin-controlled background diet.

Conditions

ADME

Keywords

Epicatechin; Flavanols; Procyanidins; Polyphenols; Phytonutrients; AMDE; Antioxidants

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

Controlled dietary background & (-)-[2-14C]epicatechin intake

Group Type: EXPERIMENTAL

Controlled dietary background

Intervention Type: OTHER

Controlled dietary flavanol-/procyanidin- background, consisting of daily intake for 14 days (day -17 to -4) of a commercially available flavanol-/procyanidin-containing cocoa-based drink (250 mg cocoa flavanols; 40 mg of (-)-epicatechin) followed by a 4-day period (day -4 to 0) of a low-flavanol diet.

(-)-[2-14C]epicatechin intake

Intervention Type: OTHER

Single oral intake of an aqueous solution of a mixture of non-radiolabeled (-)-epicatechin and a single-carbon-14 radiolabeled (-)-\[2-14C\]epicatechin. The target amount of EC delivered with test drink will be 60 mg, 58.5 mg of which consist of non-radiolabled EC and 1.54 mg (300 µCi) consist of (-)-\[2-14C\]epicatechin.

Interventions

Controlled dietary background

Controlled dietary flavanol-/procyanidin- background, consisting of daily intake for 14 days (day -17 to -4) of a commercially available flavanol-/procyanidin-containing cocoa-based drink (250 mg cocoa flavanols; 40 mg of (-)-epicatechin) followed by a 4-day period (day -4 to 0) of a low-flavanol diet.

Intervention Type: OTHER

(-)-[2-14C]epicatechin intake

Single oral intake of an aqueous solution of a mixture of non-radiolabeled (-)-epicatechin and a single-carbon-14 radiolabeled (-)-\[2-14C\]epicatechin. The target amount of EC delivered with test drink will be 60 mg, 58.5 mg of which consist of non-radiolabled EC and 1.54 mg (300 µCi) consist of (-)-\[2-14C\]epicatechin.

Intervention Type: OTHER

Other Intervention Names

(-)-cis-3,3',4',5,7-Pentahydroxyflavane; (2R,3R) - 2- (3,4- Dihydroxyphenyl) - 3,4- dihydro- 1(2H) - benzopyran- 3,5,7- triol

Eligibility Criteria

Inclusion Criteria

1. males, in good health, between 18 and 50 years of age and between 60 and 100 kg;

2. body mass index (BMI) between 19 and 30 kg/m2.

3. clinical laboratory evaluations (including clinical chemistry [fasted at least 10 hours], hematology, and urinalysis) within the reference range for the testing laboratory, unless deemed not clinically significant by the Investigator;

4. negative hepatitis panel (including hepatitis B surface antigen [HbsAg] and hepatitis C virus antibody [anti-HCV]) and human immunodeficiency virus (HIV) antibody screens;

5. a minimum of 1 bowel movement per day.

Exclusion Criteria

1. history or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urological, or psychiatric disorders;

2. allergies to peanuts, nuts, or other foods;

3. lactose intolerance;

4. history of stomach or intestinal surgery, except that appendectomy or hernia were allowed;

5. history of alcoholism or drug addiction within 1 year prior to study entry (ie, at Screening);

6. use of any tobacco products (including cigarette, pipe, cigar, chewing, nicotine patch, or nicotine gum) within 6 months prior to study entry;

7. use of any agents (excluding those provided as part of this study procedure) affecting the liver enzymes;

8. use of aspirin-containing drugs and any other over-the-counter, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) during the study, unless deemed acceptable by the Investigator;

9. use of any alcohol-containing or caffeine-containing products/medications within 72 hours prior to (-)-[2-14C]epicatechin ingestion;

10. regular consumption of more than 2 alcoholic drinks per day;

11. vegans, vegetarians and/or anyone who consumed less than 1 to 2 servings of fruits and or vegetables per day;

12. participation in more than one other radiolabeled investigational study drug trial within 12 months prior to study entry or exposure to significant radiation within 12 months prior to study entry;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Covance

INDUSTRY

Sponsor Role: collaborator

Mars, Inc.

INDUSTRY

Sponsor Role: collaborator

The Institutes for Pharmaceutical Discovery, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christine L Hale, MD

Role: PRINCIPAL_INVESTIGATOR

Covance Clinical Pharmacology Inc.

Michael Fare

Role: STUDY_DIRECTOR

IPD, LLC

Javier I Ottaviani, Ph.D.

Role: STUDY_DIRECTOR

Mars, Inc.

Locations

Covance Clinical Pharmacology Inc.

Madison, Wisconsin, United States

Countries

United States

References

Ottaviani JI, Borges G, Momma TY, Spencer JP, Keen CL, Crozier A, Schroeter H. The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives. Sci Rep. 2016 Jul 1;6:29034. doi: 10.1038/srep29034.

Reference Type: DERIVED

PMID: 27363516 (View on PubMed)

Other Identifiers

8215022

Identifier Type: -

Identifier Source: org_study_id