The Effects of Types of Fruits and Vegetables on Vascular Function (CIRCUS)

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

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.

Study Overview

• Status: Completed
• Conditions: Blood Pressure; Vascular Stiffness; Cardiovascular Risk Factor
• Intervention / Treatment: Other: LFV; Other: HFV; Other: CC

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom
    • Cambridge Epidemiology & Trials Unit
  • London, United Kingdom, W12 0HS
    • Imperial/NIHR Clinical Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Low Fruits and Vegetables (LFV); 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; 1 apple/banana/small bunch of grapes per day plus 1 portion of carrot/pepper/tomato per day
Experimental: High Fruits and Vegetables (HFV); 4 portions of fruits plus 4 portions of vegetables, of commonly consumed types per day excluding citrus fruits, cruciferous and allium vegetables.	Other: HFV; 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.
Experimental: High Citrus fruits and Cruciferous vegetables (CC); 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; 4 portions of citrus fruits (clementines, grapefruits, lemons, oranges) plus 4 portions of cruciferous vegetables (broccoli, brussels sprouts, cauliflower, kale, savoy cabbage) per day.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Cambridge
• Collaborators: Imperial College London
• Investigators: Principal Investigator: Linda Oude Griep, PhD, MRC Epidemiology Unit, University of Cambridge

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2017
• Primary Completion (Actual): June 21, 2021
• Study Completion (Actual): June 21, 2021

Study Registration Dates

• First Submitted: December 3, 2017
• First Submitted That Met QC Criteria: January 24, 2018
• First Posted (Actual): January 25, 2018

Study Record Updates

• Last Update Posted (Actual): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Blood Pressure; Vascular Stiffness; Cardiovascular Risk Factor; Fruit and vegetable
• Other Study ID Numbers: 17HH3878; Research Ethics Committee (Registry Identifier: 17/LO/0862)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: As describe in study protocol
• IPD Sharing Time Frame: In a timely manner when results have been published in peer-reviewed journals.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No