Nitrate INFORMER Nitrosamine Study

March 30, 2022 updated by: Edith Cowan University

Randomised Controlled Trial to Investigate N-nitrosamine Formation After Meat Intake - Pilot Study of the Nitrate INFORMER Studies; Nitrate INFORMER Studies: Is Nitrosamine FORMation dEpenent on souRce

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.

A pilot study will be conducted to determine that endogenous N-nitrosamine formation is observed after ingestion of meat with added nitrate and nitrite and that consumption of vegetables with the meat containing added nitrate and nitrite will inhibit the production of N-nitrosamines.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study design:

A crossover study design will be used with a 1-week washout period. Each participant will complete the scheduled study visits for one of the dietary interventions which will be assigned in random order. Following the washout, the participants will then complete the scheduled study visits for the remaining intervention. Participants will be provided with a low nitrate and N-nitrosamine meal on the preceding evening of each study visit. These meals will be consistent across all study visits. Participants will be asked to refrain from drinking coffee and any alcoholic beverage and doing any exercise 24 hours prior to the study visit.

Dietary interventions:

Meat with added nitrate: Prosciutto/pancetta/Parma ham/salami (all derived from pork) prepared by a commercial butcher with sodium nitrate as an additive.

Meat with added nitrate plus vegetables: The same intervention described above consumed together with mixed vegetables.

Assessments:

At each clinic visit, baseline samples of urine will be collected for measurement of N-nitrosamines, nitrate, and nitrite. After the intervention, all urine within the first 240 minutes and then subsequent 20-hour period will be collected for measurement of N-nitrosamines, nitrate, and nitrite.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Royal Perth Hospital Research Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Six healthy, ambulant, community-dwelling men and women aged between 18 to 55 years old and with no history of major chronic disease will be recruited from the Perth general population.

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Meat with added nitrate
Prosciutto/pancetta/Parma ham/salami (all derived from pork) prepared by a commercial butcher with sodium nitrate as an additive.
Dietary supplement: Meat with added nitrate
Prosciutto/pancetta/Parma ham/salami (all derived from pork) prepared by a commercial butcher with the sodium nitrate and nitrite as an additive.
Experimental: Meat with added nitrate plus vegetables
The same intervention as of Arm "meat with added nitrate" consumed together with mixed vegetables.
Dietary supplement: Meat with added nitrate plus vegetables
The same intervention as of intervention "meat with added nitrate" consumed together with mixed vegetables.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
N-nitrosamines in urine post each intervention after 4 hours up till 24 hours
Time Frame: After each clinic visit, all urine from 4-hour to 24-hour period will be collected.
Participants will be provided with a sterilized container and instructions to collect all urine from 4 hours until 24 hours post intervention. Urine aliquots will be frozen at -80°C until analysis. Level of N-nitrosamines will be measured by gas chromatography mass spectrometry (GCMS).
After each clinic visit, all urine from 4-hour to 24-hour period will be collected.
N-nitrosamines in urine pre each intervention
Time Frame: At each clinic visit, baseline samples of urine will be collected.
Participants will be provided with a sterilized container and instructions to collect the first urine sample of the day which will be brought into the clinic. Urine aliquots will be frozen at -80°C until analysis. Level of N-nitrosamines will be measured by gas chromatography mass spectrometry (GCMS).
At each clinic visit, baseline samples of urine will be collected.
N-nitrosamines in urine post each intervention up to 240 min
Time Frame: At each clinic visit, all urine samples within the first 240 min will be collected.
Participants will be provided with a sterilized container and instructions to collect all urine until 4 hours post intervention. Urine aliquots will be frozen at -80°C until analysis. Level of N-nitrosamines will be measured by gas chromatography mass spectrometry (GCMS).
At each clinic visit, all urine samples within the first 240 min will be collected.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Edith Cowan University

Collaborators

Flinders University
The University of Western Australia

Investigators

  • Principal Investigator: Catherine P Bondonno, PhD, RNutr., Edith Cowan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 11, 2021

Primary Completion (Actual)

December 31, 2021

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

August 30, 2021

First Submitted That Met QC Criteria

September 15, 2021

First Posted (Actual)

September 16, 2021

Study Record Updates

Last Update Posted (Actual)

April 1, 2022

Last Update Submitted That Met QC Criteria

March 30, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

  • 2021-02629-BONDONNO(pilot)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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