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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05710341




Registration number
NCT05710341
Ethics application status
Date submitted
24/01/2023
Date registered
2/02/2023
Date last updated
13/09/2023

Titles & IDs
Public title
Nitrate INFORMER Water Study
Scientific title
Randomised Controlled Trial to Investigate N-nitrosamine Formation After Water Intake
Secondary ID [1] 0 0
2022-03891-BONDONNO
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Health Risk Behaviors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Water with added nitrate
Other interventions - Water without added nitrate

Active Comparator: Water with added nitrate - 137 mg sodium nitrate or 164 mg potassium nitrate (100mg of nitrate) in a 500 mL water bottle (200 mg/L) provided twice, one with breakfast and one with lunch. This is equivalent to 200mg nitrate in total.

Placebo Comparator: Water without added nitrate - 137 mg sodium chloride or 164 mg potassium chloride in a 500 mL water bottle provided twice, one with breakfast and one with lunch.


Other interventions: Water with added nitrate
Water with added nitrate

Other interventions: Water without added nitrate
Water without added nitrate
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
N-nitrosamines in urine post intervention (up to 24 hours)
Timepoint [1] 0 0
At each clinic visit, all urine from the start of intervention up till 24 hours will be collected.
Primary outcome [2] 0 0
N-nitrosamines in stool samples post intervention (up to 24 hours)
Timepoint [2] 0 0
At each clinic visit, all stool samples from the start of intervention up till 24 hours will be collected.

Eligibility
Key inclusion criteria
The recruitment will be as inclusive as possible so that the results are relevant to much
of the general population. Twenty-five men and women will be recruited from the Perth
general population according to the following criteria:

- aged between 18 to 70 years old

- healthy, ambulant, community-dwelling

- with no history of major chronic disease
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Individuals volunteering to participate in the study will be excluded according to the
following criteria:

- current or recent (<12 months) smoking

- body mass index (BMI) <18 or > 35 kg/m2

- systolic blood pressure > 160 mmHg

- diastolic blood pressure > 100 mmHg

- any major illness such as cancer, psychiatric illness, diagnosed diabetes

- use of any of the following medications: statins, antihypertensives, nitric oxide
donors, antithrombotic medication, anti-coagulant medication, anti-arrhythmic drugs,
beta-blockers, regular aspirin use, regular proton pump inhibitor use

- alcohol consumption > 30g/day

- who are pregnant, lactating, or wishing to become pregnant during the study

- use of antibiotics within the previous 12 weeks of the study

- regular use of mouthwash and not willing to cease mouthwash use for the duration of
the study participation on other research studies

- major gastrointestinal tract condition e.g. Crohns disease and inflammatory bowel
disease 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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/05/2023
Sample size
Target
Accrual to date
Final
25
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Royal Perth Hospital Research Foundation - Perth
Recruitment postcode(s) [1] 0 0
6000 - Perth

Funding & Sponsors
Primary sponsor type
Other
Name
Edith Cowan University
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The University of Western Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Flinders University
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Nitrate is a controversial component of vegetables, meat, and drinking water. The now
well-established benefits of nitrate, through the enterosalivary nitrate-nitrite-nitric oxide
(NO) pathway, on cardiovascular risk factors and long-term cardiovascular disease risk are
tarnished by a continuing concern about a link between nitrate ingestion and cancer. This can
result in misguided advice to avoid consumption of high-nitrate leafy green vegetables by
both the media and the scientific literature. A recent media headline stated, "Cancer alert
over rocket: trendy salad leaves exceed safe levels of carcinogenic nitrates in one in every
ten samples". One scientific review stated, "the presence of nitrate in vegetables, as in
water and generally in other foods, is a serious threat to man's health". Controversy in the
literature, and gaps in the knowledge are leading to confusing messages around vegetables
that may play a critical role in cardiovascular health.

The major dietary sources of nitrate are vegetables, meat, and drinking water. Source of
nitrate could be a crucial factor determining whether the consumption of nitrate is linked
with beneficial (such as improving cardiovascular health) versus harmful (N-nitrosamine
formation) effects. For example, unlike meat and water-derived nitrate, vegetables contain
high levels of vitamin C and/or polyphenols that may inhibit the production of
N-nitrosamines. So far, no study has investigated the formation of N-nitrosamines after
consumption of these different sources in humans. This study will compare N-nitrosamine
formation after intake of water with and without added nitrate.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05710341
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Catherine Bondonno, PhD
Address 0 0
Edith Cowan University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries