The Effects of Types of Fruits and Vegetables on Vascular Function

Study Overview
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Brief Summary
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The CIRCUS study is a randomised controlled, cross-over trial to evaluate the effects of increased intakes of citrus fruits and cruciferous vegetables on vascular function in 36 untreated, prehypertensive participants.

Detailed Description
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The study comprises three 14-day dietary intervention periods, preceded by one week run-in period and separated by one week wash-out periods, 9 weeks in total. The diet will be fully controlled and provided by the researchers. Participants will receive in random order three interventions: 1 portion of fruits plus 1 portion of vegetables, of commonly consumed types per day. Intakes are at 25th percentile of UK consumption and will exclude citrus fruits, cruciferous and allium vegetables. 4 portions of fruits plus 4 portions of vegetables, of commonly consumed types per day excluding citrus fruits, cruciferous and allium vegetables. 4 portions of citrus fruits plus 4 portions of cruciferous vegetables per day.

Official Title
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The Effects of Types of Fruits and Vegetables on Vascular Function in Prehypertensive Participants: a Pilot Study

Conditions
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Blood Pressure, Vascular Stiffness, Cardiovascular Risk Factor

Intervention / Treatment
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* Other: LFV
* Other: HFV
* Other: CC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 40 - 65 years Average systolic blood pressure of 125-140 mmHg at 2 measurements separated by >30 minutes No use of antihypertensive medication No reported current or previous diabetes mellitus, (secondary) hypertension, or metabolic, cardiovascular, renal, liver, thyroid, gastrointestinal diseases Body Mass Index between 20 - 35 kg/m2 Non-smoker Average fruit and vegetable consumption of <4 portions per day (UK average, 40-65 years), or willing to reduce habitual daily fruit and vegetable intake. Exclusion Criteria: Any medication likely to interfere with energy metabolism, appetite regulation and hormonal balance. Excessive alcohol intake of > 21 units per week (females) or >28 units per week (male) and not willing to limit alcohol intake to maximum of 1 unit/day Physical activity of >=10 hours/week of moderate to vigorous physical activity Weight loss or gain of >=3 kg in the preceding 3 months Use of dietary supplements or unwilling to stop supplement use >= 2 weeks before enrolment and during intervention Pregnancy or lactation Intervention specific factors, including: Unable or unwilling to consume provided diets during the intervention Unsufficient storage space for provided diets Food sensitivities or vegetarian/vegan diet by choice Participation in another intervention study at the same time Living > 15 miles from the Imperial/NIHR Clinical Research Facility at Hammersmith Hospital No signed informed consent

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Low Fruits and Vegetables (LFV)<br>1 portion of fruits plus 1 portion of vegetables, of commonly consumed types per day. Intakes are at 25th percentile of UK consumption (NDNS) and will exclude citrus fruits, cruciferous and allium vegetables. | Other: LFV<br>* 1 apple/banana/small bunch of grapes per day plus 1 portion of carrot/pepper/tomato per day<br>|
| Experimental: High Fruits and Vegetables (HFV)<br>4 portions of fruits plus 4 portions of vegetables, of commonly consumed types per day excluding citrus fruits, cruciferous and allium vegetables. | Other: HFV<br>* 4 portions of fruits (apples, bananas, grapes, pears) plus 4 portions of vegetables (carrots, cucumber, sweet peppers, tomatoes), of commonly consumed types per day excluding citrus fruits, cruciferous and allium vegetables.<br>|
| Experimental: High Citrus fruits and Cruciferous vegetables (CC)<br>4 portions of citrus fruits plus 4 portions of cruciferous vegetables per day excluding any other types of fruits and vegetables including allium vegetables. | Other: CC<br>* 4 portions of citrus fruits (clementines, grapefruits, lemons, oranges) plus 4 portions of cruciferous vegetables (broccoli, brussels sprouts, cauliflower, kale, savoy cabbage) per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Changes in systolic and diastolic blood pressure (mmHg) measured by automated oscillometric device (average of 3 measurements). | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial stiffness | Changes (end minus baseline values) in arterial stiffness (pulse wave analysis) | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 
| Markers of cardiometabolic health measured in fasted blood samples | e.g. high-density lipoprotein | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 
| Markers of endothelial function measured in fasted blood samples | e.g. C-Reactive Protein | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 
| Markers of low-grade inflammation measured in fasted blood samples | e.g. Interleukin-6 | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 
| Urinary metabolic profiles | (Un)targeted metabolic profiling by NMR and MS | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 
| Circulatory metabolic profiles | (Un)targeted metabolic profiling by NMR and MS | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 
| Established objective markers of food intake | e.g. vitamin C | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 
| Faecal microbiome composition | Measured by 16SrRNA gene sequencing | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 
| Cognitive function | e.g. Stroop-test | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 
| Self-rated general health and mental well-being | e.g. Positive and Negative Affect Schedule (PANAS) that consists of two 10-item scales to measure both positive and negative affect. Each item is rated on a Likert scale of 1 (not at all) to 5 (very much). Positive and negative affect scores are added seperately to a reange from 10 to 50. Higher positive scores represents higher levels of positive affect. Lower negative scores respresaent lower levels of negative affect. | Measured on the morning after each of three recurring run-in periods and after each of three recurring 2-week intervention periods, 6 times total during 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood Pressure, Vascular Stiffness, Cardiovascular Risk Factor, Fruit and vegetable