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Trial registered on ANZCTR


Registration number
ACTRN12615000194561
Ethics application status
Approved
Date submitted
22/01/2015
Date registered
27/02/2015
Date last updated
25/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Vegetable intake and blood pressure study
Scientific title
The effects of daily consumption of vegetables on blood pressure in prehypertensive and stage 1 hypertensive individuals
Secondary ID [1] 286032 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
ViaBP study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular disease 294002 0
Hypertension 294099 0
Condition category
Condition code
Cardiovascular 294299 294299 0 0
Hypertension
Diet and Nutrition 294300 294300 0 0
Other diet and nutrition disorders
Mental Health 294301 294301 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A randomised, controlled, cross-over trial will be conducted to investigate the effects of different types of vegetables on blood pressure and arterial stiffness.

Each participant will complete three intervention diets of 4 weeks each in random sequence. The first intervention diet will be preceded by a 4 week lead in (washout) period. The first, second and third intervention diets will be separated by a 4 week wash out period.

The intervention diets are:
1. High nitrate diet (~400 mg per day) – with an increase in high-nitrate vegetables (lettuce – all types, spinach, rocket, Chinese leafy greens, other leafy greens, celery, and beetroot). This will involve the consumption of two blended high-nitrate vegetable juices each day: one before breakfast and one before dinner.
2. Low nitrate diet (~100-150 mg per day) – with an increase in low-nitrate vegetables (cauliflower, capsicum, sweet potato, cucumber, tomato, and parsnip). This will involve the consumption of two blended low-nitrate vegetable juices each day: one before breakfast and one before dinner.
3. Low nitrate diet (control diet, ~100 mg per day) – without an increase in vegetables. This will involve the consumption of two blended juice drinks without vegetables each day, matched in energy to juices in diets 1 and 2: one before breakfast and one before dinner.

Participants will be provided with personal blenders and advised on which vegetables/ingredients to buy and blend themselves (all meals will be maintained as usual with the exception of limiting nitrate-rich vegetables where possible). Adherence to the intervention diets will be monitored using juice checklist diaries; food intake questionnaires; and blood, urine and saliva samples.

Participants will attend 9 visits over a period of 6-8 months at the School of Medicine and Pharmacology Research Unit at Royal Perth Hospital.
Intervention code [1] 291013 0
Lifestyle
Intervention code [2] 291090 0
Treatment: Other
Intervention code [3] 291091 0
Prevention
Comparator / control treatment
Low nitrate diet (control diet) – without an increase in vegetables. This will involve the consumption of blended juice without vegetables, matched in energy to the two diets with vegetable juices.
Control group
Active

Outcomes
Primary outcome [1] 294104 0
24 hour ambulatory blood pressure measured using a Spacelabs Medical Ambulatory Blood Pressure Monitor.
Timepoint [1] 294104 0
Performed at baseline and post visits of each intervention period (total of 6 time points).
Primary outcome [2] 294105 0
Home blood pressure measured using an automated brachial cuff sphygmomanometer.
Timepoint [2] 294105 0
Performed by participants daily throughout the entire study duration (24 weeks).
Primary outcome [3] 294203 0
Blood pressure response to cognitive stress.

Cognitive stress will be induced using a computerized Cognitive Demand Battery that has been utilized in previous studies and shown to be sensitive to effects of non-pharmaceutical interventions.
Timepoint [3] 294203 0
Performed at baseline and post visits of each intervention period (total of 6 time points). Continuous blood pressure measurements will be performed for 30 minutes using the Finapres NOVA device during the period of cognitive stress.
Secondary outcome [1] 312515 0
Arterial stiffness measured as pulse wave velocity and augmentation index using the SphygomoCor XCEL device.
Timepoint [1] 312515 0
Performed at baseline and post visits of each intervention period (total of 6 time points).
Secondary outcome [2] 312759 0
Measures of working memory. This is a composite outcome assessed using the Cognitive Demand Battery which comprises two computerized serial subtraction tasks and a Rapid Visual Information Processing task.
Timepoint [2] 312759 0
Performed at baseline and post visits of each intervention period (total of 6 time points).
Secondary outcome [3] 313159 0
Measure of mood assessed using the Bond-Lader Visual Analogue Mood Scale.
Timepoint [3] 313159 0
Performed at baseline and post visits of each intervention period (total of 6 time points).

Eligibility
Key inclusion criteria
Ambulant men and women;
21-75 years; and
Systolic blood pressure 120-160 mm Hg.
Minimum age
21 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Systolic blood pressure less than 120 mm Hg or greater than 160 mm Hg;
Diastolic blood pressure greater than 100 mm Hg;
Diagnosed type 1 or 2 diabetes or fasting glucose greater than 7.0mmol/L;
Consumption of a diet estimated to contain greater than 200 mg/day of nitrate (volunteers willing to limit nitrate-rich vegetables for a period of 4 weeks before their lead in visit may be included);
Consumption of greater than or equal to 5 serves of vegetables per day;
Being vegan or vegetarian;
Body mass index less than 18.5 kg/m2 and body mass index greater than or equal to 35 kg/m2;
Use of antihypertensive medication;
Use of nitric oxide donors, organic nitrites and nitrates, sildenafil and/or related drugs;
Use of antibacterial mouth wash (volunteers willing to cease using antibacterial mouth wash for a period of 4 weeks before their lead in visit may be included);
Use of antibiotics (within previous 2 months);
Current or recent (less than 12 months) smoking;
History of symptomatic cardiovascular or peripheral vascular disease or chronic kidney disease;
Recent history of a psychiatric illness or other major illnesses such as cancer;
A change in drug therapy likely to influence blood pressure or major secondary outcomes within the previous 3 months, and/or the likelihood that drug therapy would change during the study;
Current or recent (within previous 6 months) significant weight loss or gain (greater than 6% of body weight);
Alcohol intake greater than 140 g per week for women or greater than 210 g per week for men and/or binge drinking behaviour;
Reported participation in night shift work during the study period;
Breastfeeding, pregnancy or planning of pregnancy; and
Inability or unwillingness to follow the study protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible participants will be randomly assigned to one of 6 sequence orders using computer generated random numbers. 50 sealed opaque envelopes, numbered 1-50, each containing one of the 6 sequence orders for intervention diets will be used for randomisation by opening an envelope, in consecutive order, as participants are entered into the study. The computer generated random numbers and sealed opaque envelopes will be completed and held by a person independent of study researchers within the University of Western Australia. The study coordinator will contact the person independent of study researchers to obtain the next available envelope once an individual is deemed eligible. The envelope will be opened and the code will be recorded
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated random numbers using Microsoft Excel.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical analyses will be performed according to a pre-specified statistical analysis plan using IBM SPSS Statistics Version 21 (2012, Armonk, NY: IBM Corp.); SAS software (Version 9.3: SAS Institute Inc); or STATA 12 (StataCorp). The primary analysis will be modified intention to treat (all randomised participants for which we have collected baseline data). Analysis will be performed using mixed models (including all available data). The level of significance will be set at p < 0.05 for a two-tailed test.
A sample size of 25 participants has been calculated on the primary outcome of blood pressure assessed as 24-hr ambulatory blood pressure. 25 participants will provide >80% power to detect a 2.0 mm Hg difference in mean 24-hour systolic blood pressure assuming a within-group SD of 15 mm Hg, and a minimum of 50 blood pressure measurements over 24 hours per subject. This calculation is based on a between group comparison of means using a type I error rate of 0.05/3 (0.017).
In addition, we will have >80% power to detect a 2.0 mm Hg difference in mean home systolic blood pressure assuming a within-group SD of 15 mm Hg based on our previous studies, and a minimum of 50 blood pressure measurements per subject at each time point (baseline and post).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 3358 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 9137 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 290622 0
Government body
Name [1] 290622 0
National Health and Medical Research Council
Address [1] 290622 0
GPO Box 1421
Canberra ACT 2601
Country [1] 290622 0
Australia
Primary sponsor type
University
Name
The University of Western Australia
Address
35 Stirling Highway
Crawley WA 6009
Country
Australia
Secondary sponsor category [1] 289307 0
None
Name [1] 289307 0
Address [1] 289307 0
Country [1] 289307 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292250 0
The University of Western Australia Human Research Ethics Committee
Ethics committee address [1] 292250 0
35 Stirling Highway
Crawley WA 6009
Ethics committee country [1] 292250 0
Australia
Date submitted for ethics approval [1] 292250 0
Approval date [1] 292250 0
18/06/2014
Ethics approval number [1] 292250 0
RA/4/1/6782

Summary
Brief summary
High blood pressure is a leading risk factor for mortality. Diet and lifestyle change, which can reduce the need for costly blood pressure medication, can have the largest potential impact on high blood pressure in the community. Large randomised controlled trials demonstrate that consumption of diets rich in plant foods (fruits, vegetables, legumes and whole grains) lower blood pressure. We propose that the amount and type of vegetables consumed is important for blood pressure, and that focused advice to consume nitrate-rich vegetables will result in lower blood pressure. Acute and very short-term studies clearly demonstrate that an increase in nitrate intake can significantly reduce blood pressure. The objective of this study is to establish if these effects on blood pressure are sustained over a 4 week period. In a separate investigation we also wish to determine if daily consumption of nitrate-rich vegetables can lower the cardiovascular response to stress. Secondary objectives of this study are to explore the role of nitrate-rich vegetables in improving blood vessel stiffness and cognitive function and mood.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 54322 0
Prof Jonathan Hodgson
Address 54322 0
The University of Western Australia
School of Medicine and Pharmacology
GPO Box X2213
Perth WA 6847
Country 54322 0
Australia
Phone 54322 0
+61 8 9224 0267
Fax 54322 0
Email 54322 0
jonathan.hodgson@uwa.edu.au
Contact person for public queries
Name 54323 0
Ms Lauren Blekkenhorst
Address 54323 0
The University of Western Australia
School of Medicine and Pharmacology
GPO Box X2213
Perth WA 6847
Country 54323 0
Australia
Phone 54323 0
+61 8 9224 0381
Fax 54323 0
Email 54323 0
lauren.blekkenhorst@research.uwa.edu.au
Contact person for scientific queries
Name 54324 0
Ms Lauren Blekkenhorst
Address 54324 0
The University of Western Australia
School of Medicine and Pharmacology
GPO Box X2213
Perth WA 6847
Country 54324 0
Australia
Phone 54324 0
+61 8 9224 0381
Fax 54324 0
Email 54324 0
lauren.blekkenhorst@research.uwa.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary