Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000417785
Ethics application status
Approved
Date submitted
11/04/2013
Date registered
15/04/2013
Date last updated
10/12/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Short-term effects on blood pressure of reducing nitrate metabolism using antibacterial mouthwash in treated hypertensive individuals
Scientific title
Short-term effects on blood pressure of reducing nitrate metabolism using antibacterial mouthwash in treated hypertensive individuals
Secondary ID [1] 282312 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular disease 288854 0
Hypertension 288855 0
Condition category
Condition code
Cardiovascular 289196 289196 0 0
Hypertension
Diet and Nutrition 289197 289197 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 3 days each in random order. These will be separated by a 10 to 12 day washout period. The 3 day intervention periods will correspond to use of either an antibacterial mouth wash (20 ml with 2mg/mL chlorhexidine gluconate) or plain tap water (20 ml) to rinse the mouth after brushing teeth. This will be performed twice daily: in the morning after breakfast; and in the evening after dinner. On each occasion participants will wash their mouth with 20 ml of mouthwash or plain tap water by swishing and gargling for 30 seconds, and then spitting out. During one of the 3 day periods participants will use the mouthwash and the other 3 day period they will use plain tap water. The order of the two periods will be random. Adherence to use of the moutwash/water will be established by participant diaries and measurement of nitrate reduction in the mouth. Throughout each 3 day intervention period participants will be asked to measure their blood pressure at home each day in the morning (shortly after waking), during the afternoon (at a convenient time) and during the evening (shortly before going to sleep). Three home blood pressure measurements, with a 1 minute interval between measurements, will be performed at each time each day (a total of nine blood pressure measurements each day). Participants will be provided with instructions regarding these measurements. The aim is to determine if reducing nitrate metabolism to nitrite (the precursor of NO) using antibacterial mouthwash will alter blood pressure. The antibacterial mouth wash can temporarily reduce the number of bacterial on the tongue that can reduce nitrate to nitrite. On the morning of day 4, at the end of each 3 day intervention period, (visit 2 and visit 3) participants will visit attend the School of Medicine and Pharmacology at the Royal Perth Hospital once for approximately 1.5 hours. Participants do not need to fast, but are asked to have the same breakfast meal prior to each visit. Prescribed medication will be taken as usual. At each of the two visits participants will: *Have a 15 ml fasting blood sample (approximately 3 teaspoons) taken to measure the metabolism of the nitrate, and to measure biochemical factors related to blood pressure. * Provide a 5 minute saliva sample. *Have the nitrate reduction by the bacteria in the mouth tested. This will involve holding a water and a nitrate solution in the mouth for 5 minutes each, before spitting them into a collection vessel. *Have arterial (blood vessel) stiffness measured using the CR2000 device. * Bring in the home blood pressure monitor for downloading of blood pressure measurements from the previous 3 days.
Intervention code [1] 286927 0
Treatment: Other
Comparator / control treatment
Water
Control group
Placebo

Outcomes
Primary outcome [1] 289308 0
Home blood pressure measured using a home blood pressure monitor.
Timepoint [1] 289308 0
Mean home blood pressure during 3-day intervention period
Secondary outcome [1] 302197 0
Measures of nitrate metabolism. Participants will have a 15 ml fasting blood sample taken and provide a 5 minute saliva sample to measure the metabolism of nitrate, by measuring nitrate and nitrite concentrations. The nitrate reduction by the bacteria in the mouth tested by holding a nitrate solution in the moth and measuring nitrate and nitrite levels.
Timepoint [1] 302197 0
End of 3-day intervention
Secondary outcome [2] 302198 0
Measures of arterial stiffness assessed as large and small artery elasticity index measured using the CR2000 device.
Timepoint [2] 302198 0
End of 3-day intervention.

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
Sex
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
Open (masking not used)
Who is / are masked / blinded?



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
20/05/2013
Actual
1/02/2013
Date of last participant enrolment
Anticipated
27/09/2013
Actual
27/09/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
25
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 287074 0
Government body
Name [1] 287074 0
National Health and Medical Research Council
Country [1] 287074 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] 285849 0
None
Name [1] 285849 0
Address [1] 285849 0
Country [1] 285849 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289089 0
University of Westren Australia Human Research Ethics Committee
Ethics committee address [1] 289089 0
The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009
Ethics committee country [1] 289089 0
Australia
Date submitted for ethics approval [1] 289089 0
Approval date [1] 289089 0
05/04/2013
Ethics approval number [1] 289089 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 importance of nitrate reduction by bacteria in the mouth for the control of level of blood pressure in treated hypertensive individuals.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 39198 0
Prof Jonathan Hodgson
Address 39198 0
University of Western Australia (UWA) School of Medicine and Pharmacology, GPO Box X2213, Perth, WA 6847
Country 39198 0
Australia
Phone 39198 0
61 (0)8 9224 0267
Fax 39198 0
Email 39198 0
Jonathan.Hodgson@uwa.edu.au
Contact person for public queries
Name 39199 0
Prof Jonathan Hodgson
Address 39199 0
UWA School of Medicine and Pharmacology, GPO Box X2213, Perth, WA 6847
Country 39199 0
Australia
Phone 39199 0
61 (0)8 9224 0267
Fax 39199 0
Email 39199 0
Jonathan.Hodgson@uwa.edu.au
Contact person for scientific queries
Name 39200 0
Prof Jonathan Hodgson
Address 39200 0
UWA School of Medicine and Pharmacology, GPO Box X2213, Perth, WA 6847
Country 39200 0
Australia
Phone 39200 0
61 (0)8 9224 0267
Fax 39200 0
Email 39200 0
Jonathan.Hodgson@uwa.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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