Condition category
Mental and Behavioural Disorders
Date applied
22/07/2013
Date assigned
22/07/2013
Last edited
30/06/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The era of general dietary recommendations for the whole population may be coming to an end, as it is becoming apparent that we are all unique and do not respond in the same way to the same foods. Within a decade it is believed that individuals at risk of specific conditions will be easily identified and accordingly may be recommended personalised nutrition based on their genetic make-up. At the University of East Anglia we are interested in particular food compounds known as flavonoids which can be found in plant-based foods including fruits, tea and chocolate. The aim of this study is to determine whether the processing of flavonoids in the human body (absorption, distribution, metabolism and elimination [ADME]) differs between individuals depending on age, gender, genetic make-up or the bacteria present in the gut.

Who can participate?
As part of this study, the researchers are aiming to recruit European Caucasian men and women (non-smokers) who are aged either 18-30 or 65-77 years and are generally healthy.

What does the study involve?
Volunteers involved in the study will first follow a dietary restriction by avoiding fruits, vegetables, wholegrain foods, tea, coffee or fruit juice for 3 days before the main study day (Day 4). On Day 4 they will be asked to have a test meal consisting of a bar of chocolate and a glass of juice made from freeze dried blackberries and an extract of orange, which are rich in flavonoids. They will then be asked to donate blood on Days 4 and 5 and provide urine samples on Days 3, 4 and 5. They will also be asked to provide a faecal sample on either Day 3 or the morning of Day 4 before consumption of the test meal. All foods will be provided on Days 4 and 5. The volunteers will need to visit the clinical research facility a total of five times for the entire study (including a consent visit and a screening visit). Most of the visits will take less than 1 hour each except for Day 4 (main study visit) which will be about 8 hours long. Travel expenses will be reimbursed and the volunteers will receive £25 for their time.

What are the possible benefits and risks of participating?
This is a nutritional intervention study and as such there will be no direct benefit to the participants in taking part in this study. However, the volunteers may benefit from knowing their blood chemistry and blood pressure results as part of the screening process for this study. There are no expected adverse effects of the intervention in this study, as the naturally occurring compounds are presented in food sources readily consumed in the habitual diet and at doses which can be readily achieved through normal dietary practices. As a safeguard, participants will be asked at screening whether they have known allergy to the study foods (chocolate, orange juice, blackberries).

Where is the study run from?
The study will be conducted within the Clinical Research Facility at the Medical School of the University of East Anglia, Norwich (UK).

When is the study starting and how long is it expected to run for?
The study will start in July 2013 and is expected to be completed by September 2014.

Who is funding the study?
The study has been funded by the Biotechnology and Biological Sciences Research Council (BBSRC), UK.

Who is the main contact?
Professor Anne Marie Minihane
A.Minihane@uea.ac.uk

Trial website

http://www.cobstudy.org/

Contact information

Type

Scientific

Primary contact

Prof Anne Marie Minihane

ORCID ID

Contact details

Department of Nutrition
Norwich Research Park
Medical School
Norwich
NR4 7 TJ
United Kingdom
A.Minihane@uea.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01922869

Protocol/serial number

14638

Study information

Scientific title

A human acute flavonoid intervention study to examine flavonoid metabolism and the effect on memory/cognition

Acronym

COB

Study hypothesis

Investigation of the genetic and phenotypic determinants of flavonoid absorption and metabolism. Assessing the influence of age, sex, gut microbiota and host genetics on inter-personal differences in flavonoid metabolism.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=14638

Ethics approval

East of England, Norfolk, Research Ethics Committee, 13/EE/0066

Study design

Non-randomised interventional trial

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

GP practices

Trial type

Treatment

Patient information sheet

Participants information can be found at http://www.cobstudy.org/what-is-the-study-about

Condition

Topic: Primary Care Research Network for England; Subtopic: Not Assigned; Disease: All Diseases

Intervention

Mixed flavonoid source, food source of a mixture of flavonoids.

The study will be an acute nutritional intervention study. Volunteers will be asked to consume one dose of a flavonoid rich test meal, consisting of chocolate and a juice made from freeze dried blackberry powder and an extract of orange, providing approximately 640 mg of flavan-3-ols, 390 mg of anthocyanins and 342 mg of flavanones. The study takes 5 days in total, including 3 days of dietary restriction and 2 days of follow-up after the flavonoid rich test meal administration.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

The primary outcome measure for the study will be the measurement of the concentrations of flavonoids and their metabolites in blood and urine. They will be assessed in samples provided before the administration of the flavonoid rich test meal (24 hour pre-administration urine and a blood sample immediately before test meal administration) and several times after the test meal administration (7 regular blood samples over a 24 hour period and 2 x 24 hour urine, to be collected up to 48 hours after the test meal administration).

Flavonoids and their metabolites will be assessed using state-of-the-art liquid chromatography-tandem mass spectrometry (LC-MS/MS) and quantified against commercially available standards. Serum and urine will be acidified and then extracted by solid phase extraction (SPE). Metabolite identification will be performed using a QTrap 4000 linear ion trap mass spectrometer (ABSciex, Canada) by multi-reaction monitoring (MRM) optimized for the detection of pure standards. Metabolites will be confirmed on the basis of retention time and parent-daughter ion fragmentation transitions.

Secondary outcome measures

The secondary outcome measure for the study will be to investigate the influence of gut microbiota variation on flavonoid absorption and metabolism. To do this, we will collect faecal samples and determine gut-microflora using faecal bacterial phylogenetic analysis using PCR to amplify 16S rDNA genes. Faecal samples will be collected within 24 hours before the administration of the flavonoid rich test meal.

Overall trial start date

08/07/2013

Overall trial end date

31/07/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Men and women
2. 18-30 years or 65-77 years
3. White Caucasian, of European origin
4. Non-smokers
5. Gnerally healthy

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 240; UK Sample Size: 240; Description: 18-30yrs (n=120) and 65-77yrs (n=120). Generally healthy, caucasian and non-smoker.

Participant exclusion criteria

1. Smoke
2. Are pregnant, have been pregnant in the last year or are breastfeeding
3. Have any existing medical conditions or significant past medical history likely to affect study measurements e.g., type 2 diabetes, cardiovascular, renal, liver, gastrointestinal diseases
4. Are on medication that may affect the study outcome
5. Have used antibiotics within the last three months
6. Have had vaccinations within the last three months
7. Take certain dietary supplements or herbal remedies and are unwilling to stop taking them
8. Have been involved in another research project within the last 3 months
9. Are unable to provide written informed consent
10. Have donated blood in the 16 weeks prior to the start of this study or intend to donate blood in the 16 weeks following this study
11. Have body mass index (BMI, kg/m2) <18.5
12. Have body mass index (BMI, kg/m2) >30
13. Have blood pressure < 90/60 mmHg
14. Have blood pressure > 140/90 mmHg

Recruitment start date

08/07/2013

Recruitment end date

31/07/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Nutrition
Norwich
NR4 7 TJ
United Kingdom

Sponsor information

Organisation

University of East Anglia (UK)

Sponsor details

Research and Enterprise Services
Norwich
NR4 7 TJ
United Kingdom
Deborah.Graver@uea.ac.uk

Sponsor type

University/education

Website

http://www.uea.ac.uk/

Funders

Funder type

Research council

Funder name

Biotechnology and Biological Sciences Research Council (BBSRC) (UK) Grant Codes: BB-J004545-1

Alternative name(s)

BBSRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes