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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05886023




Registration number
NCT05886023
Ethics application status
Date submitted
23/05/2023
Date registered
2/06/2023
Date last updated
16/04/2024

Titles & IDs
Public title
Nitrate INFORMER Vegetable Study
Scientific title
Randomised Controlled Trial to Investigate N-nitrosamine Formation After Vegetable Intake
Secondary ID [1] 0 0
2023-04297-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
Treatment: Other - High nitrate vegetables
Treatment: Other - Low nitrate vegetables

Active comparator: Active Intervention - The intervention comprises vegetable burger containing high nitrate vegetables (100g of spinach, \~1000mg/kg FW nitrate) on white bread sandwich, provided at breakfast and lunch.

Placebo comparator: Control Intervention - The intervention comprises vegetable burger containing low nitrate vegetables (200g of peas, sweet corn, \< 30 mg/kg FW nitrate) on white bread sandwich, provided at breakfast and lunch.


Treatment: Other: High nitrate vegetables
Vegetable burger containing high nitrate vegetables

Treatment: Other: Low nitrate vegetables
Vegetable burger containing to low nitrate vegetables
Intervention code [1] 0 0
Treatment: Other
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 75 years old
* healthy, ambulant, community-dwelling
* with no history of major chronic disease
Minimum age
18 Years
Maximum age
75 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
26/06/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/10/2023
Sample size
Target
Accrual to date
Final
27
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 vegetables with high nitrate content and vegetables with a low nitrate content.
Trial website
https://clinicaltrials.gov/study/NCT05886023
Trial related presentations / publications
Lundberg JO, Weitzberg E. NO-synthase independent NO generation in mammals. Biochem Biophys Res Commun. 2010 May 21;396(1):39-45. doi: 10.1016/j.bbrc.2010.02.136.
Blekkenhorst LC, Bondonno NP, Liu AH, Ward NC, Prince RL, Lewis JR, Devine A, Croft KD, Hodgson JM, Bondonno CP. Nitrate, the oral microbiome, and cardiovascular health: a systematic literature review of human and animal studies. Am J Clin Nutr. 2018 Apr 1;107(4):504-522. doi: 10.1093/ajcn/nqx046.
Spiegelhalder B, Eisenbrand G, Preussmann R. Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds. Food Cosmet Toxicol. 1976 Dec;14(6):545-8. doi: 10.1016/s0015-6264(76)80005-3. No abstract available.
Gangolli SD, van den Brandt PA, Feron VJ, Janzowsky C, Koeman JH, Speijers GJ, Spiegelhalder B, Walker R, Wisnok JS. Nitrate, nitrite and N-nitroso compounds. Eur J Pharmacol. 1994 Nov 1;292(1):1-38. doi: 10.1016/0926-6917(94)90022-1.
Blekkenhorst LC, Prince RL, Ward NC, Croft KD, Lewis JR, Devine A, Shinde S, Woodman RJ, Hodgson JM, Bondonno CP. Development of a reference database for assessing dietary nitrate in vegetables. Mol Nutr Food Res. 2017 Aug;61(8). doi: 10.1002/mnfr.201600982. Epub 2017 May 3.
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05886023