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

NCT03201822 | Completed

• 1 other identifier: 429275
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

flavanol; ADME; cocoa flavanols; polyphenols

Outcome Measures

Primary Outcomes (4)

• Change in levels of gut microbiome derived metabolites in urine

  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

  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

  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

  Structurally related epicatechin metabolites include sulfated, glucuronidated and/or methylated metabolites of epicatechin

  Plasma collected before (0h) and up to 6h post intervention

Secondary Outcomes (11)

• Composite of pharmacokinetic (PK) parameters of metabolites Maximum Plasma Concentration (CMax)

  Before intervention (0h) and up to 24 h after intervention

• Composite of pharmacokinetic (PK) parameters of metabolites Time to Maximum Plasma Concentration

  Before intervention (0h) and up to 24 h after intervention

• Composite of pharmacokinetic (PK) parameters of metabolites Area Under the Curve

  Before intervention (0h) and up to 24 h after intervention

• Composite of pharmacokinetic (PK) parameters of metabolites Area Under the Curve extrapolated to infinity

  Before intervention (0h) and up to 24 h after intervention

• Composite of pharmacokinetic (PK) parameters of metabolites Elimination Rate Constant

  Before intervention (0h) and up to 24 h after intervention

Study Arms (4)

100 mg of Cocoa Flavanols/70 kg BW

EXPERIMENTAL

Fruit flavored non-dairy drink containing 100 cocoa flavanol/70 kg BW

Other: 100 mg of Cocoa Flavanols/70 kg BW

200 mg of Cocoa Flavanols/70 kg BW

EXPERIMENTAL

Fruit flavored non-dairy drink containing 200 cocoa flavanol/70 kg BW

Other: 200 mg of Cocoa Flavanols/70 kg BW

400 mg of Cocoa Flavanols/70 kg BW

EXPERIMENTAL

Fruit flavored non-dairy drink containing 400 cocoa flavanol/70 kg BW

Other: 400 mg of Cocoa Flavanols/70 kg BW

1000 mg of Cocoa Flavanols/70 kg BW

EXPERIMENTAL

Fruit flavored non-dairy drink containing 1000 cocoa flavanol/70 kg BW

Other: 1000 mg of Cocoa Flavanols/70 kg BW

Interventions

100 mg of Cocoa Flavanols/70 kg BW OTHER

Fruit-flavored non-dairy drink containing 100 cocoa flavanols/70kg BW.

100 mg of Cocoa Flavanols/70 kg BW

200 mg of Cocoa Flavanols/70 kg BW OTHER

Fruit-flavored non-dairy drink containing 200 cocoa flavanols/70kg BW.

200 mg of Cocoa Flavanols/70 kg BW

400 mg of Cocoa Flavanols/70 kg BW OTHER

Fruit-flavored non-dairy drink containing 400 cocoa flavanols/70kg BW.

400 mg of Cocoa Flavanols/70 kg BW

1000 mg of Cocoa Flavanols/70 kg BW OTHER

Fruit-flavored non-dairy drink containing 1000 cocoa flavanols/70kg BW.

1000 mg of Cocoa Flavanols/70 kg BW

Eligibility Criteria

• Age: 25 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of California, Davis: lead
• Mars, Inc.: collaborator

Study Sites (1)

UC Davis

Davis, California, 95616, United States

Location

Related Publications (5)

• Schroeter H, Heiss C, Spencer JP, Keen CL, Lupton JR, Schmitz HH. Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs. Mol Aspects Med. 2010 Dec;31(6):546-57. doi: 10.1016/j.mam.2010.09.008. Epub 2010 Sep 18.

  PMID: 20854838 BACKGROUND

• Ottaviani JI, Momma TY, Kuhnle GK, Keen CL, Schroeter H. Structurally related (-)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards. Free Radic Biol Med. 2012 Apr 15;52(8):1403-12. doi: 10.1016/j.freeradbiomed.2011.12.010. Epub 2011 Dec 23.

  PMID: 22240152 BACKGROUND

• Koster H, Halsema I, Scholtens E, Knippers M, Mulder GJ. Dose-dependent shifts in the sulfation and glucuronidation of phenolic compounds in the rat in vivo and in isolated hepatocytes. The role of saturation of phenolsulfotransferase. Biochem Pharmacol. 1981 Sep 15;30(18):2569-75. doi: 10.1016/0006-2952(81)90584-0. No abstract available.

  PMID: 6946775 BACKGROUND

• McCullough ML, Chevaux K, Jackson L, Preston M, Martinez G, Schmitz HH, Coletti C, Campos H, Hollenberg NK. Hypertension, the Kuna, and the epidemiology of flavanols. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S103-9; discussion 119-21. doi: 10.1097/00005344-200606001-00003.

  PMID: 16794446 BACKGROUND

• Heiss C, Kleinbongard P, Dejam A, Perre S, Schroeter H, Sies H, Kelm M. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J Am Coll Cardiol. 2005 Oct 4;46(7):1276-83. doi: 10.1016/j.jacc.2005.06.055.

  PMID: 16198843 BACKGROUND

Study Officials

• Carl L Keen, PhD

  UC Davis

  PRINCIPAL INVESTIGATOR

• Javier I Ottaviani, PhD

  Mars, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-masked and cross-over dietary intervention study in healthy young adult males

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 28, 2017
• Study Start: April 1, 2013
• Primary Completion: May 25, 2013
• Study Completion: May 25, 2013
• Last Updated: June 28, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)