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Trial registered on ANZCTR


Registration number
ACTRN12613000116729
Ethics application status
Approved
Date submitted
29/01/2013
Date registered
31/01/2013
Date last updated
14/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Short-term effects of a high nitrate intake on blood pressure in treated hypertensive individuals
Scientific title
Short-term effects of a high nitrate intake on blood pressure in treated hypertensive individuals
Secondary ID [1] 281862 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cardiovascular disease 288236 0
Hypertension 288237 0
Condition category
Condition code
Cardiovascular 288595 288595 0 0
Hypertension
Diet and Nutrition 288596 288596 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A randomised, controlled, cross-over designed trial will be performed. Each participant will complete 2 intervention periods of 1 week each in random order. These will be separated by a 2 week washout period. The two 1 week intervention periods will correspond to:
1. Active – high nitrate intake: consumption of 1X70 ml/d (35 ml with breakfast and 35 ml with dinner) of a concentrated beetroot juice beverage containing approximately 200 mg of nitrate per dose (400 mg total for the day)
2. Placebo – control: consumption of 1X70 ml/d (35 ml with breakfast and 35 ml with dinner) of a concentrated beetroot juice containing <5 mg of nitrate (<10 mg total for the day)
Participants and researchers will be blinded to treatment. The 400 mg dose of nitrate represents an upper level of nitrate intake achievable via dietary means.
At the end of each 1 week intervention period, participants will collect a 24 h urine sample, then attend School of Medicine and Pharmacology Research Unit at Royal Perth Hospital in the morning (after a 12 h fast) for approximately 3 h. During this time:
* A fasting blood sample will be collected for measurement of nitrate and nitrite concentrations, and biochemical markers related to vascular function.
* Participants will then be provided with a standard low nitrate breakfast to be consumed over 20 minutes.
* Participants will consume one 70 ml dose of the assigned beverage with breakfast.
* An ambulatory blood pressure monitor will be fitted 30 minutes after breakfast. The monitor will record blood pressure every 20 min during the day and every 30 min overnight for the following 24 h.
* A saliva sample will be collected 2 h after breakfast for measurement of nitrate and nitrite concentrations.
* Participants will then go about normal daily activities, avoiding vigorous physical activity.
* A second dose of the assigned beverage will be taken with dinner, and a third dose will be taken with breakfast the next morning.
* For each participant, the timing of the visits will be on the same day of the week at the same time of day as far as possible.
* Participants will return to the School of Medicine and Pharmacology Research Unit the next morning, after breakfast, to have the blood pressure monitor removed.
In addition, daily throughout each 1 week intervention period participants will perform home blood pressure monitoring. These measurements will be performed between 2 and 3 hours after the dinner meal, shortly before going to sleep. Five home blood pressure measurements will be performed at this time each day. This will provide information regarding the time-course of any effects on blood pressure. Throughout the study period the background diet will be the participant’s usual diet.
Intervention code [1] 286423 0
Treatment: Other
Comparator / control treatment
Placebo (beetroot juice with nitrate removed)
Control group
Placebo

Outcomes
Primary outcome [1] 288747 0
24 h ambulatory blood pressure
Timepoint [1] 288747 0
1 week
Secondary outcome [1] 300894 0
Home blood pressure level measured daily throughout the intervention using a validated home blood pressure measurement device
Timepoint [1] 300894 0
mean during 1 week intervention period

Eligibility
Key inclusion criteria
* Men and women will be aged between 50 and 70 years
* Regular use of at least one antihypertensive medication for elevated blood pressure
* Clinic/office systolic blood pressure will be >120 mmHg
Minimum age
50 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Use of more than 3 antihypertensive medications
* A change in antihypertensive medication within the past 1 month
* Inability to attend clinic/office visits
* Clinic/office systolic blood pressure greater than 160 mm Hg or less than 120 mm Hg; or diastolic blood pressure greater than 100 mm Hg;
* Use of antibiotics (within previous 1 months);
* current or recent (<6 months) smoking;
* body mass index < 18 or > 35 kg/m2;
* current cardiovascular or peripheral vascular disease, or diagnosed diabetes, or history of a cardiovascular event;
* a psychiatric illness, or presence of other major illnesses such as cancer;
* current or recent (within previous 6 months) significant weight loss or gain (> 6% of body weight);
* alcohol intake > 210 g per wk for women and > 280 g per wk for men;
* pregnant or lactating women;
* inability or unwillingness to consume beverages provided.

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)
There are two treatments in the cross-over design study. 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
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)
WA

Funding & Sponsors
Funding source category [1] 286641 0
Government body
Name [1] 286641 0
National Health and Medical Research Council
Address [1] 286641 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 286641 0
Australia
Primary sponsor type
University
Name
The University of Western Australia
Address
The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009
Country
Australia
Secondary sponsor category [1] 285424 0
None
Name [1] 285424 0
Address [1] 285424 0
Country [1] 285424 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288718 0
University of Westren Australia Human Research Ethics Committee
Ethics committee address [1] 288718 0
The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009
Ethics committee country [1] 288718 0
Australia
Date submitted for ethics approval [1] 288718 0
Approval date [1] 288718 0
14/11/2012
Ethics approval number [1] 288718 0
RA/4/1/5624

Summary
Brief summary
There is now consistent and convincing evidence that dietary inorganic nitrate plays an important role in the physiological control of blood pressure. Clinical trials have established that an increase in nitrate intake, either from supplements or vegetables, results in a dose-related decrease in blood pressure in healthy normotensive individuals. This trial will address the question: "Can ingestion of a diet high in nitrate lower blood pressure in treated hypertensive individuals?"
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 37450 0
Prof Jonathan Hodgson
Address 37450 0
UWA School of Medicine and Pharmacology, GPO Box X2213, Perth, WA 6847
Country 37450 0
Australia
Phone 37450 0
61 (0)8 9224 0267
Fax 37450 0
61 (0)8 9224 0246
Email 37450 0
Jonathan.Hodgson@uwa.edu.au
Contact person for public queries
Name 37451 0
Prof Jonathan Hodgson
Address 37451 0
UWA School of Medicine and Pharmacology, GPO Box X2213, Perth, WA 6847
Country 37451 0
Australia
Phone 37451 0
61 (0)8 9224 0267
Fax 37451 0
61 (0)8 9224 0246
Email 37451 0
Jonathan.Hodgson@uwa.edu.au
Contact person for scientific queries
Name 37452 0
Prof Jonathan Hodgson
Address 37452 0
UWA School of Medicine and Pharmacology, GPO Box X2213, Perth, WA 6847
Country 37452 0
Australia
Phone 37452 0
61 (0)8 9224 0267
Fax 37452 0
61 (0)8 9224 0246
Email 37452 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