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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05075720




Registration number
NCT05075720
Ethics application status
Date submitted
30/08/2021
Date registered
13/10/2021
Date last updated
1/02/2023

Titles & IDs
Public title
Nitrate INFORMER Meat Study
Scientific title
Randomised Controlled Trial to Investigate N-nitrosamine Formation After Meat Intake - Meat Study of the Nitrate INFORMER Studies; Nitrate INFORMER Studies: Is Nitrosamine FORMation dEpenent on souRce
Secondary ID [1] 0 0
2021-02629-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 - Meat with added nitrate
Treatment: Other - Meat without added nitrate
Treatment: Other - Control

Experimental: Dietary Supplement: Meat with added nitrate - The intervention comprises 50 g salami and 35 g ham on white bread sandwich at breakfast and lunch.

This intervention will allow us to determine both endogenous formation of N-nitrosamines as well as N-nitrosamines present in the commercially prepared meat.

Experimental: Dietary Supplement: Meat without added nitrate - The intervention comprises 65 g Pork mince on white bread sandwich at breakfast and lunch. Nitrate is not an allowed additive in pork mince.

This intervention will allow us to determine if there is endogenous formation of N-nitrosamines as well as N-nitrosamines present in the prepared meat due to the natural content of nitrate in meat.

Sham comparator: Dietary Supplement: Control - The control comprises low nitrate vegetable protein burger on white bread. Protein content matched to interventions 1 and 2.


Treatment: Other: Meat with added nitrate
The intervention comprises 50 g salami and 35 g ham on white bread sandwich at breakfast and lunch.

This intervention will allow us to determine both endogenous formation of N-nitrosamines as well as N-nitrosamines present in the commercially prepared meat.

Treatment: Other: Meat without added nitrate
The intervention comprises 65 g Pork mince on white bread sandwich at breakfast and lunch. Nitrate is not an allowed additive in pork mince.

This intervention will allow us to determine if there is endogenous formation of N-nitrosamines as well as N-nitrosamines present in the prepared meat due to the natural content of nitrate in meat.

Treatment: Other: Control
The control comprises low nitrate vegetable protein burger on white bread. Protein content matched to interventions 1 and 2.
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 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
27/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/12/2022
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 meat with and without added nitrate.
Trial website
https://clinicaltrials.gov/study/NCT05075720
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.
Bondonno CP, Blekkenhorst LC, Liu AH, Bondonno NP, Ward NC, Croft KD, Hodgson JM. Vegetable-derived bioactive nitrate and cardiovascular health. Mol Aspects Med. 2018 Jun;61:83-91. doi: 10.1016/j.mam.2017.08.001. Epub 2017 Sep 7.
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.
Tannenbaum SR, Weisman M, Fett D. The effect of nitrate intake on nitrite formation in human saliva. Food Cosmet Toxicol. 1976 Dec;14(6):549-52. doi: 10.1016/s0015-6264(76)80006-5. 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.
Mirvish SS. Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC. Cancer Lett. 1995 Jun 29;93(1):17-48. doi: 10.1016/0304-3835(95)03786-V. Erratum In: Cancer Lett 1995 Nov 6;97(2):271.
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. IARC monographs on the evaluation of carcinogenic risks to humans. Ingested nitrate and nitrite, and cyanobacterial peptide toxins. IARC Monogr Eval Carcinog Risks Hum. 2010;94:v-vii, 1-412. No abstract available.
Hord NG, Tang Y, Bryan NS. Food sources of nitrates and nitrites: the physiologic context for potential health benefits. Am J Clin Nutr. 2009 Jul;90(1):1-10. doi: 10.3945/ajcn.2008.27131. Epub 2009 May 13.
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.
Bartsch H, Ohshima H, Pignatelli B. Inhibitors of endogenous nitrosation. Mechanisms and implications in human cancer prevention. Mutat Res. 1988 Dec;202(2):307-24. doi: 10.1016/0027-5107(88)90194-7.
Levallois P, Ayotte P, Van Maanen JM, Desrosiers T, Gingras S, Dallinga JW, Vermeer IT, Zee J, Poirier G. Excretion of volatile nitrosamines in a rural population in relation to food and drinking water consumption. Food Chem Toxicol. 2000 Nov;38(11):1013-9. doi: 10.1016/s0278-6915(00)00089-2.
Bartholomew B, Hill MJ. The pharmacology of dietary nitrate and the origin of urinary nitrate. Food Chem Toxicol. 1984 Oct;22(10):789-95. doi: 10.1016/0278-6915(84)90116-9.
Bondonno CP, Croft KD, Puddey IB, Considine MJ, Yang X, Ward NC, Hodgson JM. Nitrate causes a dose-dependent augmentation of nitric oxide status in healthy women. Food Funct. 2012 May;3(5):522-7. doi: 10.1039/c2fo10206d. Epub 2012 Feb 16.
Bondonno CP, Downey LA, Croft KD, Scholey A, Stough C, Yang X, Considine MJ, Ward NC, Puddey IB, Swinny E, Mubarak A, Hodgson JM. The acute effect of flavonoid-rich apples and nitrate-rich spinach on cognitive performance and mood in healthy men and women. Food Funct. 2014 May;5(5):849-58. doi: 10.1039/c3fo60590f.
Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016 Jul;13(7):581-3. doi: 10.1038/nmeth.3869. Epub 2016 May 23.
Cole JR, Wang Q, Fish JA, Chai B, McGarrell DM, Sun Y, Brown CT, Porras-Alfaro A, Kuske CR, Tiedje JM. Ribosomal Database Project: data and tools for high throughput rRNA analysis. Nucleic Acids Res. 2014 Jan;42(Database issue):D633-42. doi: 10.1093/nar/gkt1244. Epub 2013 Nov 27.
Parks DH, Chuvochina M, Waite DW, Rinke C, Skarshewski A, Chaumeil PA, Hugenholtz P. A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life. Nat Biotechnol. 2018 Nov;36(10):996-1004. doi: 10.1038/nbt.4229. Epub 2018 Aug 27.
Public notes

Contacts
Principal investigator
Name 0 0
Catherine P Bondonno, PhD, RNutr.
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/NCT05075720