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 people 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. Food compounds known as flavonoids 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 differs between individuals depending on age, gender, genetic make-up or the bacteria present in the gut.
Who can participate?
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 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 are 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 are then be asked to provide a blood sample on Days 4 and 5 and provide urine samples on Days 3, 4 and 5. They are also asked to provide a faecal sample on either Day 3 or the morning of Day 4 before eating the test meal. All foods are provided on Days 4 and 5. The volunteers 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 take less than 1 hour each except for Day 4 (main study visit) which is about 8 hours long. Travel expenses are reimbursed and the volunteers receive £25 for their time.
What are the possible benefits and risks of participating?
This is a nutritional 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?
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?
July 2013 to September 2014
Who is funding the study?
Biotechnology and Biological Sciences Research Council (BBSRC) (UK)
Who is the main contact?
Prof. Anne Marie Minihane
A.Minihane@uea.ac.uk
Trial website
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.
Ethics approval
East of England, Norfolk, Research Ethics Committee, ref: 13/EE/0066
Study design
Non-randomised interventional trial
Primary study design
Interventional
Secondary study design
Non randomised study
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
Norwich Research Park
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
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
government organisation
Funding Body Subtype
Federal/National Government
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