Effect of Apple Flavanols on Risk of Cardiovascular Disease (FLAVO)

March 5, 2013 updated by: Quadram Institute Bioscience

A randomised three period cross over trial will be carried out in adults (19-64 years) to assess the acute and chronic effects of a large dose of apple procyanidin (PA) compared with a low dose of apple PA (negative control) and aspirin (positive control), on platelet function and other risk factors of cardiovascular disease. Platelet function will be assessed prior to a run in diet and at the start and end of each intervention. Volunteers will be assigned at random to consume 230grams of low PA apple puree or high PA apple puree or aspirin (75mg) each day for 2 weeks followed by a minimum 14 day wash out.

Hypothesis: Consuming apple PA reduces platelet function consistent with reduced risk of cardiovascular disease.

Study Overview

Detailed Description

A randomised 3-period cross-over trial will be carried out to assess the acute and chronic effects of a large dose of apple PA compared with a low dose of apple PA (negative control) and aspirin (positive control), on platelet function (flow cytometry) and other risk factors of CVD (endothelial function, plasma antioxidants, inflammatory markers, lipid profile). Once recruited, volunteers will be assigned at random to consume 230g of low PA apple puree or high PA apple puree or aspirin (75mg) each day for 14 days in period 1. Following a minimum 14 day wash-out volunteers will then be crossed over for period 2 and after another 14-day wash-out volunteers will be crossed over to complete period 3 of the intervention (flow chart I). The acute effect of each treatment will be investigated on day 15 of each period. A fasting blood sample will be obtained prior to consumption of a standard breakfast and the apple puree or aspirin. Further blood samples will then be obtained at 2, 6 and 24 hours post-dosing. The chronic effect of all three treatments will be determined by measuring CVD risk factors in fasting blood samples obtained on day 1, 15 and 29. Flow chart II provides a more detailed overview of the design of each period which is identical for the apple puree treatments and differs only in the omission of urine collections and PWV measurements for the aspirin period. During the apple puree interventions phenolic acids will be analysed in 24-hour urine pools collected on the day prior to the start of each period, as well as on day 14, 15, and 28. PWV measurements will be carried on day 15 and 29 after a 12-hour overnight fast for each of the 2 apple intervention periods.

For the intervention to be successful it is necessary to exclude some food sources that contribute significantly to total PA intake (e.g. cocoa, berries, grapes, red wine, apples, legumes) and limit other PA food sources (tea/coffee) to levels that support compliance and are unlikely to mask any effects of the intervention. Because of its well documented effect on platelet function alcohol will be restricted to a maximum of 2 units per day and excluded completely for the 48 hours prior to blood sampling appointments. Oily fish consumption will be limited to 2 portions per week and will not be allowed for 48 hours prior to blood sampling. These dietary restrictions may have significant effects on platelet function in individuals that consume these foods regularly. Therefore, dietary restrictions will apply during a 14-day run-in diet prior to and for the duration of each intervention period. Platelet function will be assessed prior to the start of the run-in diet as well as at the start and end of each PA/aspirin intervention (flow chart II).

Male and female volunteers aged 19 to 64 will be recruited and screened for eligibility for up to 2 months prior to the start of the intervention. Those meeting the study criteria will be randomly assigned to one out of the six possible treatment orders, i.e. ABC, ACB, BAC, CAB, BCA, CBA. Randomisation will be stratified by sex.

Volunteers will be given a user friendly booklet (Run-in diet/Apple/Aspirin diary) for each intervention period to record apple puree/aspirin consumption and volunteers will also be prompted to record their alcohol, tea/coffee and oily fish intake (Annex 2). Foods not allowed during each intervention period are listed. Volunteers will be reminded not to consume oily fish (as listed), alcohol, coffee and tea 48 hours prior to a blood sampling appointment.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Norfolk
      • Norwich, Norfolk, United Kingdom, NR4 7UA
        • Institue of Food Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • male and female aged 19-64

Exclusion Criteria:

  • Smokers, very low or high pressure (<90/50 or <95/55 if symptomatic or >160/100), BMI <18.5 or >35, pregnant or have been pregnant in last 12 months, diagnosed with gastrointestinal disease, history of ulcers and gastrointestinal bleeding, diagnosed with a long term illness requiring active treatment, history of stroke, on regularly prescribed medication known to have a profound effect on cardiovascular disease risk factors, using non steroidal anti inflammatory cream, sufferers of asthma or hay fever, known intolerance to aspirin, allergic to apples or birch pollen, regular use of aspirin, antacids or laxatives, unwillingness to discontinue specific dietary or herbal supplements less than 1 month prior to the start of the study, blood donation within 16 weeks of the first study sample, antibiotic use within 4 weeks prior to starting the study, those who receive or plan to receive any type of immunisation within 4 weeks of the start of the study, parallel participation in any other research project.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low PA apple puree
230grams of low PA apple puree (Golden Delicious) consumed daily for 14 days.
Golden Delicious apple puree 230grams consumed daily for 14 days
Experimental: High PA apple puree
High PA apple puree (Mitchalin) 230grams consumed daily for 14 days
High PA apple puree (Mitchalin) consumed daily for 14 days
Placebo Comparator: Aspirin
75mg dispersable aspirin taken daily for 14 days
75mg dispersable aspirin taken daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The aim of this trial is to investigate the effect of consuming apple PA on platelet function.
Time Frame: 16 weeks
16 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
To measure the bioavailability of PA and metabolites from two well characterised apple purees providing a low and high dose of PA.
Time Frame: 16 weeks
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Paul Kroon, Quadram Institute Bioscience
  • Principal Investigator: Amy Gasper, Quadram Institute Bioscience

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

December 4, 2007

First Submitted That Met QC Criteria

December 4, 2007

First Posted (Estimate)

December 5, 2007

Study Record Updates

Last Update Posted (Estimate)

March 6, 2013

Last Update Submitted That Met QC Criteria

March 5, 2013

Last Verified

March 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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