NCT02353234

Brief Summary

The consumption of wholemeal cereals has been associated with the reduction of several chronic diseases. The mechanisms behind these protective effects may be linked, besides dietary fiber and micronutrients, to an increased intake of phenolic compounds, mainly, hydroxycinnamates contained in the bran. Among bran fractions, aleurone usually contains the highest concentration of ferulic acid, principally contained as monomeric form and diferulic acid esters linked to arabinoxylans, representing the most relevant subclasses. The aim of the study was to evaluate the absorption of hydroxycinnamates by measuring the urinary excretion of phenolic metabolites in humans fed with two different kind of a commercial bread, as wholegrain bread and a white bread enriched with aleurone fraction. Moreover, the pharmacokinetics of the main phenolic compounds was also evaluated by measuring the circulating metabolites in plasma samples.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Dec 2014

Shorter than P25 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2014

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

January 27, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

February 2, 2015

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2015

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2015

Completed
Last Updated

December 2, 2015

Status Verified

December 1, 2015

Enrollment Period

6 months

First QC Date

January 27, 2015

Last Update Submit

December 1, 2015

Conditions

Keywords

PhenolicsAleuroneBioavailabilityPharmacokinetics

Outcome Measures

Primary Outcomes (1)

  • Phenolic compound bioavailability in wholegrain bread compared with bread enriched with aleurone fraction (urine samples will be filtered and diluted and phenolic compound metabolites will be identified)

    Volunteers will collect urine before consuming bread (T0) and for 48 hours after the consumption of the meal test, in each study arms. Urine samples will be collected and stored at -80°C until uHPLC/MS analysis. Prior analysis, urine samples will be filtered and diluted and phenolic compound metabolites will be identified. Expected Metabolites: Coumaric acid, Hydroxyphenylpropionic acid, Dihydroxyphenylacetic acid, Hippuric acid, Enterolactone, Enterodiol, Coumaric acid sulphate, Phenylpropionic acid sulphate, Vanillic acid sulphate, Hydroxyphenylpropionic acid sulphate, Ferulic acid sulphate, Dihydroferulic acid sulphate, Hydroxyphenylpropionic acid glucuronide, Ferulic acid glucuronide, Enterolactone sulphate, Enterodiol sulphate, Enterolactone glucuronide, Enterodiol glucuronide.

    0h; 0-3h; 3-6h; 6-10h; 10-14h; 14-24h; 24-28h; 28-34h; 34-48h.

Secondary Outcomes (1)

  • Phenolic compound pharmacokinetics in wholegrain bread compared with bread enriched with aleurone fraction (metabolites identified in Plasma samples that will be collected prior (T0) and after bread consumption in each study arms.)

    0h; 0.5h; 1h; 2h; 4h; 7h; 24h.

Study Arms (3)

WHOLEGRAIN BREAD

ACTIVE COMPARATOR

Subjects feed with wholegrain bread, for which ferulic acid content has been quantified.

Other: Bread

WHITE BREAD WITH ALEURONE - 4

ACTIVE COMPARATOR

Subjects feed with white bread with aleurone fraction in the same portion as wholegrain bread.

Other: Bread

WHITE BREAD WITH ALEURONE - 8

ACTIVE COMPARATOR

Subjects feed with white bread with aleurone fraction, which contains the same quantity of ferulic acid as wholegrain bread.

Other: Bread

Interventions

BreadOTHER

In each arm subjects consume bread

WHITE BREAD WITH ALEURONE - 4WHITE BREAD WITH ALEURONE - 8WHOLEGRAIN BREAD

Eligibility Criteria

Age18 Years - 30 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • BMI 18-25 kg/m2

You may not qualify if:

  • Pregnancy and breastfeeding
  • diagnosis of celiac disease
  • diagnosed methabolic diseases (diabetes and disorders of glycaemic control, hypertension, dyslipidemia)
  • sustained use of nutritional supplements of vitamins, in particular E and C, at the recruitment step
  • chronic pharmacological therapy
  • antibiotic therapy during the last 40 days

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Parma - Department of Food Science

Parma, 43125, Italy

Location

Related Publications (11)

  • Anson NM, Selinheimo E, Havenaar R, Aura AM, Mattila I, Lehtinen P, Bast A, Poutanen K, Haenen GR. Bioprocessing of wheat bran improves in vitro bioaccessibility and colonic metabolism of phenolic compounds. J Agric Food Chem. 2009 Jul 22;57(14):6148-55. doi: 10.1021/jf900492h.

    PMID: 19537710BACKGROUND
  • Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A. Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal. 2013 May 10;18(14):1818-92. doi: 10.1089/ars.2012.4581. Epub 2012 Aug 27.

    PMID: 22794138BACKGROUND
  • Gabrielsson J, Weiner D. Non-compartmental analysis. Methods Mol Biol. 2012;929:377-89. doi: 10.1007/978-1-62703-050-2_16.

    PMID: 23007438BACKGROUND
  • Kikuzaki H, Hisamoto M, Hirose K, Akiyama K, Taniguchi H. Antioxidant properties of ferulic acid and its related compounds. J Agric Food Chem. 2002 Mar 27;50(7):2161-8. doi: 10.1021/jf011348w.

    PMID: 11902973BACKGROUND
  • Calani L, Ounnas F, Salen P, Demeilliers C, Bresciani L, Scazzina F, Brighenti F, Melegari C, Crozier A, de Lorgeril M, Del Rio D. Bioavailability and metabolism of hydroxycinnamates in rats fed with durum wheat aleurone fractions. Food Funct. 2014 Aug;5(8):1738-46. doi: 10.1039/c4fo00328d.

    PMID: 24977665BACKGROUND
  • Luceri C, Giannini L, Lodovici M, Antonucci E, Abbate R, Masini E, Dolara P. p-Coumaric acid, a common dietary phenol, inhibits platelet activity in vitro and in vivo. Br J Nutr. 2007 Mar;97(3):458-63. doi: 10.1017/S0007114507657882.

    PMID: 17313706BACKGROUND
  • Mateo Anson N, Hemery YM, Bast A, Haenen GR. Optimizing the bioactive potential of wheat bran by processing. Food Funct. 2012 Apr;3(4):362-75. doi: 10.1039/c2fo10241b. Epub 2012 Feb 15. No abstract available.

    PMID: 22336890BACKGROUND
  • Stalmach A, Mullen W, Barron D, Uchida K, Yokota T, Cavin C, Steiling H, Williamson G, Crozier A. Metabolite profiling of hydroxycinnamate derivatives in plasma and urine after the ingestion of coffee by humans: identification of biomarkers of coffee consumption. Drug Metab Dispos. 2009 Aug;37(8):1749-58. doi: 10.1124/dmd.109.028019. Epub 2009 May 21.

    PMID: 19460943BACKGROUND
  • Stalmach A, Steiling H, Williamson G, Crozier A. Bioavailability of chlorogenic acids following acute ingestion of coffee by humans with an ileostomy. Arch Biochem Biophys. 2010 Sep 1;501(1):98-105. doi: 10.1016/j.abb.2010.03.005. Epub 2010 Mar 11.

    PMID: 20226754BACKGROUND
  • Truswell AS. Cereal grains and coronary heart disease. Eur J Clin Nutr. 2002 Jan;56(1):1-14. doi: 10.1038/sj.ejcn.1601283.

    PMID: 11840174BACKGROUND
  • Zaupa M, Scazzina F, Dall'Asta M, Calani L, Del Rio D, Bianchi MA, Melegari C, De Albertis P, Tribuzio G, Pellegrini N, Brighenti F. In vitro bioaccessibility of phenolics and vitamins from durum wheat aleurone fractions. J Agric Food Chem. 2014 Feb 19;62(7):1543-9. doi: 10.1021/jf404522a. Epub 2014 Feb 6.

    PMID: 24450764BACKGROUND

MeSH Terms

Interventions

Bread

Intervention Hierarchy (Ancestors)

FoodDiet, Food, and NutritionPhysiological PhenomenaFood and Beverages

Study Officials

  • Daniele Del Rio, Professor

    University of Parma

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

January 27, 2015

First Posted

February 2, 2015

Study Start

December 1, 2014

Primary Completion

June 1, 2015

Study Completion

July 1, 2015

Last Updated

December 2, 2015

Record last verified: 2015-12

Locations