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Trial registered on ANZCTR


Registration number
ACTRN12611000609954
Ethics application status
Approved
Date submitted
13/06/2011
Date registered
14/06/2011
Date last updated
12/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Can nitrate-rich green leafy vegetables lower blood pressure?
Scientific title
Can nitrate-rich green leafy vegetables lower blood pressure in men and women with high-normal blood pressure?
Secondary ID [1] 262364 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Blood pressure 268068 0
Vascular function 268069 0
Condition category
Condition code
Cardiovascular 268213 268213 0 0
Hypertension
Diet and Nutrition 268214 268214 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A randomised, controlled, cross-over design trial will be performed.

Trial periods
1. Run-in (washout) period: 1 week.
All participants will begin the trial consuming a low nitrate/low green leafy vegetable (usual) diet (containing less than ~100 mg/d of nitrate).

2. First intervention period: 1 week.
Participants will then either: continue on the low nitrate diet; or increase the intake of green leafy vegetables resulting in an estimated nitrate intake of greater than 400 mg/d.

3. Washout period: 1 week.
As for 1 above

4. Second intervention period: 1 week.
As for 2 above

The order of the two interventions (low nitrate; high nitrate) will be randomized.


Diets
1. The low nitrate (usual) diet will involve reducing green leafy vegetables as well as a limited number of other foods rich in nitrate (beetroot, celery, parsley) in the diet, but only if this is required to limit nitrate intake to less than ~100 mg/d. The average nitrate intake in Western populations is often well under 100 mg/d, so for most participants there will be minimal change to their diet and nitrate intake; and

2. The high nitrate diet will involve adding green leafy vegetables to the diet. Leafy greens added to the diet will include: spinach (dried and powdered, fresh and frozen); lettuce (all types); rocket; and Chinese greens (such as bok choy; choy sum, Chinese cabbage). To enhance compliance participants will be provided with all intervention foods (frozen and fresh).The objective will be to include at least 300 g/d of green leafy vegetables into the diet, increasing estimated nitrate intake to greater than 400 mg/d. A dietitian will provide individual advice on how to include the green leafy vegetables without altering energy or macronutrient intakes.
Intervention code [1] 266758 0
Treatment: Other
Intervention code [2] 266765 0
Prevention
Intervention code [3] 266766 0
Lifestyle
Comparator / control treatment
Low nitrate diet
Control group
Active

Outcomes
Primary outcome [1] 268951 0
Blood pressure: ambulatory blood pressure assessed using a Spacelabs monitor (Spacelabs Medical Inc. Redmond, WA, USA)
Timepoint [1] 268951 0
Measured at the end of each 1 week washout and intervention period as 10-hour day time ambulatory blood pressure, with blood pressure and heart rate measured every 20 minutes.
Primary outcome [2] 268952 0
Blood pressure: home monitored blood pressure assessed using an A&D home blood pressure monitor
Timepoint [2] 268952 0
Measured twice daily thoughout the entire study period
Secondary outcome [1] 276675 0
Vascular function assessed as arterial pulse wave velocity using the SphygmoCor CPV system
Timepoint [1] 276675 0
Measured at the end of each 1 week washout and intervention period
Secondary outcome [2] 276676 0
Blood plasma and saliva nitrogen oxides and related compounds.
Timepoint [2] 276676 0
Measured at the end of each 1 week washout and intervention period and 48 hour after the end of each 1 week intervention period
Secondary outcome [3] 276677 0
Biomarkers of inflammation such as HS-CRP assessed using routine methods and oxidative stress assessed by measuring plasma isoprostanes using GC-MS
Timepoint [3] 276677 0
Measured at the end of each 1 week washout and intervention period

Eligibility
Key inclusion criteria
Men and women aged 20 to 70 years with high-normal blood pressure (systolic blood pressure 120-139 mm Hg or diastolic blood pressure 80-89 mm Hg)
Minimum age
20 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Use of antihypertensive medication; systolic blood pressure < 120 mm Hg or > 139 mm Hg and diastolic blood pressure <80 mm Hg or >89 mm Hg; a diet high in green leafy vegetables; use of antibacterial mouth wash (which kills bacteria responsible for nitrate reduction in the mouth); use of antibiotics (within previous 2 months); current or recent (<12 months) smoking; history of cardiovascular or peripheral vascular disease; recent history of a psychiatric illness or other major illnesses such as cancer; recent history of asthma, renal, liver or gastrointestinal disease, or gout; a change in drug therapy within the previous 3 months, or the likelihood that drug therapy would change during the study; current or recent (within previous 6 months) significant weight loss or gain (> 6% of body weight); alcohol intake > 140 g per wk; reported participation in night shift work during the study period; and inability or unwillingness to follow the study protocol.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The treatment order for eligible individuals will be randomly assigned using computer generated random numbers. The treatment order allocation will be sealed in numbered envelopes. The envelopes will be used for randomisation by opening an envelope, in consecutive order, as participants are entered into the study. The envelopes will be held by an independent person within the University of Western Australia. The study coordinator will contact the independent person 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

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)

Funding & Sponsors
Funding source category [1] 267241 0
Government body
Name [1] 267241 0
National Health and Medical Research Council
Address [1] 267241 0
National Health and Medical Research Council, GPO Box 1421, Canberra, ACT 2601
Country [1] 267241 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009
Country
Australia
Secondary sponsor category [1] 266306 0
None
Name [1] 266306 0
Address [1] 266306 0
Country [1] 266306 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269232 0
University of Westren Australia Human Research Ethics Committee
Ethics committee address [1] 269232 0
The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009
Ethics committee country [1] 269232 0
Australia
Date submitted for ethics approval [1] 269232 0
Approval date [1] 269232 0
28/04/2011
Ethics approval number [1] 269232 0
RA/4/4669

Summary
Brief summary
The primary objective of this study is to determine if regular consumption of nitrate-rich green leafy vegetables can reduce blood pressure in men and women with high-normal blood pressure. We will also investigate the claim that dietary nitrate contributes to the body’s NO stores and that these stores represent a physiologically relevant reservoir of NO.
Trial website
Trial related presentations / publications
Bondonno CP, Liu AH, Croft KD, Ward NC, Yang X, Considine MJ, Puddey IB, Woodman RJ, Hodgson JM. Short-term effects of nitrate-rich green leafy vegetables on blood pressure and arterial stiffness in individuals with high-normal blood pressure. Free Rad Biol Med 2014; 77:353-362.
Public notes

Contacts
Principal investigator
Name 32735 0
A/Prof Jonathan Hodgson
Address 32735 0
UWA School of Medicine and Pharmacology, GPO Box X2213, Perth, WA 6847
Country 32735 0
Australia
Phone 32735 0
61 (0)8 9224 0267
Fax 32735 0
Email 32735 0
Jonathan.Hodgson@uwa.edu.au
Contact person for public queries
Name 15982 0
A/Prof Jonathan Hodgson
Address 15982 0
UWA School of Medicine and Pharmacology, GPO Box X2213, Perth, WA 6847
Country 15982 0
Australia
Phone 15982 0
61 (0)8 9224 0267
Fax 15982 0
61 (0)8 9224 0246
Email 15982 0
Jonathan.Hodgson@uwa.edu.au
Contact person for scientific queries
Name 6910 0
A/Prof Jonathan Hodgson
Address 6910 0
UWA School of Medicine and Pharmacology, GPO Box X2213, Perth, WA 6847
Country 6910 0
Australia
Phone 6910 0
61 (0)8 9224 0267
Fax 6910 0
61 (0)8 9224 0246
Email 6910 0
Jonathan.Hodgson@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