Colon CancerPhase 1PHYTOMENCT04138654
Natural Compounds to Reduce Nitrite in Meat Products
A Phase 1 study testing Processed meat product, White meat wash-out and Processed meat products enriched with natural compounds in people with Colon Cancer, run by Maastricht University at 1 site in Netherlands.
Trial summary
The PHYTOME project (Phytochemicals to reduce nitrite in meat products) is a major European Union (EU) co-funded research project that aims to develop innovative meat products in which the food additive nitrite has been replaced by natural compounds originating from fruits and vegetables. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Colon Cancer
- What is being tested?
- Processed meat product, White meat wash-out and Processed meat products enriched with natural compounds
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteNetherlands
- Study dates
- 17 Apr 2014to 1 Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy with a Body Mass Index (BMI) between 18-25, male or female
- Between 18-70 years old
Who cannot join
- Alcohol abuse up to 6 months before participation in this research
- Current aberrations or insufficiency of kidney, liver, gut, heart or lungs
- Current presence of persistent inflammation in the gut or liver
- Current endocrine or metabolic aberrations
- Current anaemia or infection
- HIV infection or hepatitis
Show all 11Show fewer
- Use of antibiotics and other medication over the last 3 months
- Current smokers
- Vegetarians
- Pregnant women
- Participants of other intervention studies during this intervention period.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Toxicogenomics
Maastricht, (Click to Select US State), 6200MD
About this study
Official title: Natural Compounds to Reduce Nitrite in Meat Products: PHYTOME
The PHYTOME project (Phytochemicals to reduce nitrite in meat products) is a major European Union (EU) co-funded research project that aims to develop innovative meat products in which the food additive nitrite has been replaced by natural compounds originating from fruits and vegetables. These biologically active compounds, also referred to as phytochemicals, are known to contribute to improved gut health and are added to the meat as natural extracts.
In a number of meat products, carefully selected combinations of natural antioxidants and other biologically active compounds occurring in vegetables, fruits and natural extracts such as coffee and tea, will be added during meat processing. Some of these compounds possess an antimicrobial activity allowing them to replace nitrite, whereas others possess a natural red colour that may contribute to the desired appearance of the products. Also, some of these compounds are known to protect colonic cells against damaging effects of cancer causing agents that may be formed in the large intestine after meat consumption.
The PHYTOME project will develop new technologies to introduce the natural extracts during processing to different types of meat products. These techniques will guarantee good sensory quality of the product as well as microbiological safety. Once these techniques have been developed and optimized at laboratory scale, the new type of products will be produced on an industrial scale. The health promoting effects of these products will be evaluated in a human dietary intervention study with healthy volunteers. After consumption of a fully controlled diet with either relatively high amounts of the traditional meat products or products produced following the new concept, faeces and colonic material will be collected and investigated for markers of colorectal cancer risk. These investigations will be performed in close collaboration with Research Institutes in the United Kingdom, Belgium, Italy and Greece, and will make use of the newest genomics techniques that are available.
Read the detailed description
Rationale:
The aim of this project is to develop new meat processing technologies, resulting in innovative meat products that have low or no nitrite and that have been shown to contribute to improved human health. This will be achieved by introducing carefully selected mixtures of biologically compounds originating from natural plant extracts. The new meat products will be evaluated in a human dietary intervention study to establish their positive effect on cancer risk markers in colonic tissues using the newest genomics techniques available.
Objective:
This project aims to evaluate the health impact of newly developed low nitrite containing meat products using genomics markers in a human dietary intervention study.
Study design:
This study has a cross-over design with only healthy volunteers. Each participant will be asked to donate a urinal, faecal and blood sample and undergo endoscopy after each intervention period. All analyses will be done for each study group separately to examine the overall effects of nitrite levels in meat.
Study population:
All subjects will be recruited by the University of Maastricht (UM) in the province of Limburg, the Netherlands, using advertisements in local newspapers as well as other media. Healthy subjects of both sexes will be selected based on predefined inclusion criteria (BMI: 18-25; > 18 years) and randomly assigned to one of the different experimental groups.
Intervention (if applicable):
Subjects will receive a completely controlled diet with 3 different types of meat products according to the study design, with either normal levels, low or no added nitrite. After each of the three intervention periods of 15 days (300 grams meat per day) blood, urine, saliva, mouth wash and faeces will be sampled and stored appropriately at UM for later analysis. Additionally, colonic biopsies will be taken by the department of internal medicine (UM) or at the hospital of Sittard during an endoscopic examination. To evaluate the impact of nitrate in drinking water on the endogenous nitrosation processes in combination with processed red meat intake, there will be and extra intervention period of 7 days were volunteers will be asked to consume drinking water with high nitrate levels according to the Acceptable Daily Intake level (ADI: 3.7mg/kg bodyweight) in combination with 300 grams processed red meat per day. Also after this intervention period volunteers will be asked to collect a blood and saliva sample and 24h urine and faeces samples. Also, colonic biopsies will be taken by the department of internal medicine (UM) or at the hospital of Sittard during an endoscopic examination.
Main study parameters/endpoints:
- Formation of N-nitrosocompounds in human faecal and urine samples
- Reveal differences in transcriptomic and epigenomic markers after consumption of meat products enriched with natural compounds. These markers can be interpreted as an indicator of reduced cancer risk.
- Correlating gene expression changes to changes in genotoxic endpoints (DNA damage, reduction in N-Nitroso compounds (NOC)) to reveal the molecular processes involved in cancer risk reduction. The identification of molecular pathways that are crucial in the carcinogenic process will demonstrate a causal association between dietary changes and markers of carcinogenic risk.
- Conditions
- Colon Cancer
- Being tested
- Processed meat product, White meat wash-out, Processed meat products enriched with natural compounds, Drinking water containing nitrate up to acceptable daily intake level (ADI = 3.7 mg/kg bw) in combination with 300 grams of processed meat, white meat or processed meat enriched with natural compounds
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Processed meat productDietary supplement
300 grams per day during 2 weeks
White meat wash-outDietary supplement
300 grams per day during 2 weeks
Processed meat products enriched with natural compoundsDietary supplement
300 grams per day during 2 weeks
Drinking water containing nitrate up to acceptable daily intake level (ADI = 3.7 mg/kg bw) in combination with 300 grams of processed meat, white meat or processed meat enriched with natural compoundsDietary supplement
3.7 mg nitrate/kg bw per day plus 300 grams of meat for 1 week
| Study group | Role | What they receive |
|---|---|---|
| Normal nitrite levels | Experimental | Processed meat products enriched with natural compounds will contain normal nitrite levels. Receives: Dietary Supplement: Processed meat product; Dietary Supplement: White meat wash-out; Dietary Supplement: Processed meat products enriched with natural compounds; Dietary Supplement: Drinking water containing nitrate up to acceptable daily intake level (ADI = 3.7 mg/kg bw) in combination with 300 grams of processed meat, white meat or processed meat enriched with natural compounds |
| Reduced nitrite levels | Experimental | Processed meat products enriched with natural compounds will contain reduced nitrite levels Receives: Dietary Supplement: Processed meat product; Dietary Supplement: White meat wash-out; Dietary Supplement: Processed meat products enriched with natural compounds; Dietary Supplement: Drinking water containing nitrate up to acceptable daily intake level (ADI = 3.7 mg/kg bw) in combination with 300 grams of processed meat, white meat or processed meat enriched with natural compounds |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in N-nitroso compound (NOC) levels in faeces and urine measured as apparent total nitroso compounds (ATNC) between baseline levels at the start of the intervention and each intervention period
The faecal and urinal level of NOC is measured as Total Apparent Nitroso Compounds (ATNC) and used indicator of colonic endogenous nitrosation. It is known to significantly increase following strictly controlled diets high in red or processed meat.
Measured: At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks
Change in whole genome gene expression analyses in colonic biopsies and blood between baseline levels and each intervention period (transcriptomics)
Colon biopsies and blood will be analysed for transcriptomic responses to the dietary changes. This will provide information on gene expression changes in the colon epithelium that may be linked with other parameters such as faecal NOC levels. This will also identify molecular pathways that can link dietary composition to processes involved in cancer development.
Measured: At baseline, at 2 weeks, at 4 weeks, and at 6 weeks
Secondary outcomes (5)
Change in urinary nitrate and creatine levels between baseline levels at the start of the intervention and each intervention period.
Urine samples (0.25 mL) will be analysed for nitrate and urinary creatinine. Nitrate concentrations (ng/ml) will be divided by creatinine concentrations (mg/100ml) to adjust for the variable hydration of participants.
Measured: At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks
Genotyping of DNA
Blood will be collected which will be used for genotyping of single nucleotide polymorphisms associated with oxidative stress, biotransformation and DNA repair. This will provide information on the relation between genetic variations linked with other tested parameters such as faecal NOC levels.
Measured: At baseline
Change in DNA methylation analyses of DNA isolated from colonic biopsies and blood (epigenetics) between baseline levels at the start of the intervention and each intervention period
Colon biopsies and blood will be analysed for epigenomic responses to the dietary changes. This will provide information on the genes of which the DNA methylation status has changed which might explain their change in gene expression. Epigenetic changes and gene expression changes will be integrated during the analyses.
Measured: At baseline, at 2 weeks, at 4 weeks, at 6 weeks
Change in enzyme activity of nitrate reductase in saliva between baseline levels at the start of the intervention and each intervention period
Microorganisms in the mouth are able to convert nitrate to nitrite and it has been estimated that about 70% of ingested nitrite is formed in this way. Dietary interventions containing nitrate have shown to infuence the activity of the enzyme nitrate reductase.
Measured: At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks
Change in the microbiome in feacal samples and in saliva between baseline levels at the start of the intervention and each intervention period
Both saliva and fecal specimens will be used for DNA extraction and subsequent analyses. The microbiome is sensitive for dietary changes, and its composition can alter due to different exposures.
Measured: At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2019
- Study start17 Apr 2014
- Primary completion30 Jun 2015
- Study completion1 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (38)Papers the sponsor has linked to this study.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04138654
- Sponsor's protocol ID
- NL43956.068.13
- Acronym
- PHYTOME
- Status last verified
- Jan 2014
- First submitted
- 8 Jan 2014
- Last updated
- 24 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
de Oliveira CE, Stamford TL, Gomes Neto NJ, de Souza EL. Inhibition of Staphylococcus aureus in broth and meat broth using synergies of phenolics and organic acids. Int J Food Microbiol. 2010 Feb 28;137(2-3):312-6. doi: 10.1016/j.ijfoodmicro.2009.11.019. Epub 2009 Dec 3.
PubMed 20004993Burt S. Essential oils: their antibacterial properties and potential applications in foods--a review. Int J Food Microbiol. 2004 Aug 1;94(3):223-53. doi: 10.1016/j.ijfoodmicro.2004.03.022.
PubMed 15246235Cheng KW, Chen F, Wang M. Inhibitory activities of dietary phenolic compounds on heterocyclic amine formation in both chemical model system and beef patties. Mol Nutr Food Res. 2007 Aug;51(8):969-76. doi: 10.1002/mnfr.200700032.
PubMed 17628877Hughes R, Cross AJ, Pollock JR, Bingham S. Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation. Carcinogenesis. 2001 Jan;22(1):199-202. doi: 10.1093/carcin/22.1.199.
PubMed 11159760Lunn JC, Kuhnle G, Mai V, Frankenfeld C, Shuker DE, Glen RC, Goodman JM, Pollock JR, Bingham SA. The effect of haem in red and processed meat on the endogenous formation of N-nitroso compounds in the upper gastrointestinal tract. Carcinogenesis. 2007 Mar;28(3):685-90. doi: 10.1093/carcin/bgl192. Epub 2006 Oct 19.
PubMed 17052997Cross AJ, Major JM, Sinha R. Urinary biomarkers of meat consumption. Cancer Epidemiol Biomarkers Prev. 2011 Jun;20(6):1107-11. doi: 10.1158/1055-9965.EPI-11-0048. Epub 2011 Apr 28.
PubMed 21527577Hall CN, Badawi AF, O'Connor PJ, Saffhill R. The detection of alkylation damage in the DNA of human gastrointestinal tissues. Br J Cancer. 1991 Jul;64(1):59-63. doi: 10.1038/bjc.1991.239.
PubMed 1854628Povey AC, Badawi AF, Cooper DP, Hall CN, Harrison KL, Jackson PE, Lees NP, O'Connor PJ, Margison GP. DNA alkylation and repair in the large bowel: animal and human studies. J Nutr. 2002 Nov;132(11 Suppl):3518S-3521S. doi: 10.1093/jn/132.11.3518S.
PubMed 12421880Georgiadis P, Kaila S, Makedonopoulou P, Fthenou E, Chatzi L, Pletsa V, Kyrtopoulos SA. Development and validation of a new, sensitive immunochemical assay for O(6)-methylguanine in DNA and its application in a population study. Cancer Epidemiol Biomarkers Prev. 2011 Jan;20(1):82-90. doi: 10.1158/1055-9965.EPI-10-0788. Epub 2010 Nov 16.
PubMed 21081711MAQC Consortium; Shi L, Reid LH, Jones WD, Shippy R, Warrington JA, Baker SC, Collins PJ, de Longueville F, Kawasaki ES, Lee KY, Luo Y, Sun YA, Willey JC, Setterquist RA, Fischer GM, Tong W, Dragan YP, Dix DJ, Frueh FW, Goodsaid FM, Herman D, Jensen RV, Johnson CD, Lobenhofer EK, Puri RK, Schrf U, Thierry-Mieg J, Wang C, Wilson M, Wolber PK, Zhang L, Amur S, Bao W, Barbacioru CC, Lucas AB, Bertholet V, Boysen C, Bromley B, Brown D, Brunner A, Canales R, Cao XM, Cebula TA, Chen JJ, Cheng J, Chu TM, Chudin E, Corson J, Corton JC, Croner LJ, Davies C, Davison TS, Delenstarr G, Deng X, Dorris D, Eklund AC, Fan XH, Fang H, Fulmer-Smentek S, Fuscoe JC, Gallagher K, Ge W, Guo L, Guo X, Hager J, Haje PK, Han J, Han T, Harbottle HC, Harris SC, Hatchwell E, Hauser CA, Hester S, Hong H, Hurban P, Jackson SA, Ji H, Knight CR, Kuo WP, LeClerc JE, Levy S, Li QZ, Liu C, Liu Y, Lombardi MJ, Ma Y, Magnuson SR, Maqsodi B, McDaniel T, Mei N, Myklebost O, Ning B, Novoradovskaya N, Orr MS, Osborn TW, Papallo A, Patterson TA, Perkins RG, Peters EH, Peterson R, Philips KL, Pine PS, Pusztai L, Qian F, Ren H, Rosen M, Rosenzweig BA, Samaha RR, Schena M, Schroth GP, Shchegrova S, Smith DD, Staedtler F, Su Z, Sun H, Szallasi Z, Tezak Z, Thierry-Mieg D, Thompson KL, Tikhonova I, Turpaz Y, Vallanat B, Van C, Walker SJ, Wang SJ, Wang Y, Wolfinger R, Wong A, Wu J, Xiao C, Xie Q, Xu J, Yang W, Zhang L, Zhong S, Zong Y, Slikker W Jr. The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements. Nat Biotechnol. 2006 Sep;24(9):1151-61. doi: 10.1038/nbt1239.
PubMed 16964229Jetten MJ, Gaj S, Ruiz-Aracama A, de Kok TM, van Delft JH, Lommen A, van Someren EP, Jennen DG, Claessen SM, Peijnenburg AA, Stierum RH, Kleinjans JC. 'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):320-8. doi: 10.1016/j.taap.2012.01.009. Epub 2012 Jan 20.
PubMed 22285215Mathijs K, Brauers KJ, Jennen DG, Boorsma A, van Herwijnen MH, Gottschalk RW, Kleinjans JC, van Delft JH. Discrimination for genotoxic and nongenotoxic carcinogens by gene expression profiling in primary mouse hepatocytes improves with exposure time. Toxicol Sci. 2009 Dec;112(2):374-84. doi: 10.1093/toxsci/kfp229. Epub 2009 Sep 21.
PubMed 19770486Mathijs K, Brauers KJ, Jennen DG, Lizarraga D, Kleinjans JC, van Delft JH. Gene expression profiling in primary mouse hepatocytes discriminates true from false-positive genotoxic compounds. Mutagenesis. 2010 Nov;25(6):561-8. doi: 10.1093/mutage/geq040. Epub 2010 Jul 21.
PubMed 20650930Tannenbaum SR, Sinskey AJ, Weisman M, Bishop W. Nitrite in human saliva. Its possible relationship to nitrosamine formation. J Natl Cancer Inst. 1974 Jul;53(1):79-84. No abstract available.
PubMed 4835100Shechter H, Gruener N, Shuval HI. A micromethod for the determination of nitrite in blood. Anal Chim Acta. 1972 Jun;60(1):93-9. doi: 10.1016/S0003-2670(01)81887-0. No abstract available.
PubMed 4667452
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural Compounds to Reduce Nitrite in Meat Products: PHYTOME
- ClinicalTrials.gov ID
- NCT04138654
- Acronym / sponsor ID
- PHYTOME / NL43956.068.13
- Conditions
- Colon Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Study start
- 17 Apr 2014 (actual)
- Primary completion
- 30 Jun 2015 (actual)
- Study completion
- 1 Dec 2015 (actual)
- First posted
- 24 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The PHYTOME project (Phytochemicals to reduce nitrite in meat products) is a major European Union (EU) co-funded research project that aims to develop innovative meat products in which the food additive nitrite has been replaced by natural compounds originating from fruits and vegetables. These biologically active compounds, also referred to as phytochemicals, are known to contribute to improved gut health and are added to the meat as natural extracts.
In a number of meat products, carefully selected combinations of natural antioxidants and other biologically active compounds occurring in vegetables, fruits and natural extracts such as coffee and tea, will be added during meat processing. Some of these compounds possess an antimicrobial activity allowing them to replace nitrite, whereas others possess a natural red colour that may contribute to the desired appearance of the products. Also, some of these compounds are known to protect colonic cells against damaging effects of cancer causing agents that may be formed in the large intestine after meat consumption.
The PHYTOME project will develop new technologies to introduce the natural extracts during processing to different types of meat products. These techniques will guarantee good sensory quality of the product as well as microbiological safety. Once these techniques have been developed and optimized at laboratory scale, the new type of products will be produced on an industrial scale. The health promoting effects of these products will be evaluated in a human dietary intervention study with healthy volunteers. After consumption of a fully controlled diet with either relatively high amounts of the traditional meat products or products produced following the new concept, faeces and colonic material will be collected and investigated for markers of colorectal cancer risk. These investigations will be performed in close collaboration with Research Institutes in the United Kingdom, Belgium, Italy and Greece, and will make use of the newest genomics techniques that are available.
Detailed description
Rationale:
The aim of this project is to develop new meat processing technologies, resulting in innovative meat products that have low or no nitrite and that have been shown to contribute to improved human health. This will be achieved by introducing carefully selected mixtures of biologically compounds originating from natural plant extracts. The new meat products will be evaluated in a human dietary intervention study to establish their positive effect on cancer risk markers in colonic tissues using the newest genomics techniques available.
Objective:
This project aims to evaluate the health impact of newly developed low nitrite containing meat products using genomics markers in a human dietary intervention study.
Study design:
This study has a cross-over design with only healthy volunteers. Each participant will be asked to donate a urinal, faecal and blood sample and undergo endoscopy after each intervention period. All analyses will be done for each study group separately to examine the overall effects of nitrite levels in meat.
Study population:
All subjects will be recruited by the University of Maastricht (UM) in the province of Limburg, the Netherlands, using advertisements in local newspapers as well as other media. Healthy subjects of both sexes will be selected based on predefined inclusion criteria (BMI: 18-25; > 18 years) and randomly assigned to one of the different experimental groups.
Intervention (if applicable):
Subjects will receive a completely controlled diet with 3 different types of meat products according to the study design, with either normal levels, low or no added nitrite. After each of the three intervention periods of 15 days (300 grams meat per day) blood, urine, saliva, mouth wash and faeces will be sampled and stored appropriately at UM for later analysis. Additionally, colonic biopsies will be taken by the department of internal medicine (UM) or at the hospital of Sittard during an endoscopic examination. To evaluate the impact of nitrate in drinking water on the endogenous nitrosation processes in combination with processed red meat intake, there will be and extra intervention period of 7 days were volunteers will be asked to consume drinking water with high nitrate levels according to the Acceptable Daily Intake level (ADI: 3.7mg/kg bodyweight) in combination with 300 grams processed red meat per day. Also after this intervention period volunteers will be asked to collect a blood and saliva sample and 24h urine and faeces samples. Also, colonic biopsies will be taken by the department of internal medicine (UM) or at the hospital of Sittard during an endoscopic examination.
Main study parameters/endpoints:
- Formation of N-nitrosocompounds in human faecal and urine samples
- Reveal differences in transcriptomic and epigenomic markers after consumption of meat products enriched with natural compounds. These markers can be interpreted as an indicator of reduced cancer risk.
- Correlating gene expression changes to changes in genotoxic endpoints (DNA damage, reduction in N-Nitroso compounds (NOC)) to reveal the molecular processes involved in cancer risk reduction. The identification of molecular pathways that are crucial in the carcinogenic process will demonstrate a causal association between dietary changes and markers of carcinogenic risk.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal nitrite levels | Experimental | Dietary Supplement: Processed meat product, Dietary Supplement: White meat wash-out, Dietary Supplement: Processed meat products enriched with natural compounds, Dietary Supplement: Drinking water containing nitrate up to acceptable daily intake level (ADI = 3.7 mg/kg bw) in combination with 300 grams of processed meat, white meat or processed meat enriched with natural compoundsProcessed meat products enriched with natural compounds will contain normal nitrite levels. |
| Reduced nitrite levels | Experimental | Dietary Supplement: Processed meat product, Dietary Supplement: White meat wash-out, Dietary Supplement: Processed meat products enriched with natural compounds, Dietary Supplement: Drinking water containing nitrate up to acceptable daily intake level (ADI = 3.7 mg/kg bw) in combination with 300 grams of processed meat, white meat or processed meat enriched with natural compoundsProcessed meat products enriched with natural compounds will contain reduced nitrite levels |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy with a Body Mass Index (BMI) between 18-25, male or female
- Between 18-70 years old
Key exclusion criteria (11 listed)
- Alcohol abuse up to 6 months before participation in this research
- Current aberrations or insufficiency of kidney, liver, gut, heart or lungs
- Current presence of persistent inflammation in the gut or liver
- Current endocrine or metabolic aberrations
- Current anaemia or infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Processed meat product300 grams per day during 2 weeks | Dietary supplement | Normal nitrite levels, Reduced nitrite levels |
| White meat wash-out300 grams per day during 2 weeks | Dietary supplement | Normal nitrite levels, Reduced nitrite levels |
| Processed meat products enriched with natural compounds300 grams per day during 2 weeks | Dietary supplement | Normal nitrite levels, Reduced nitrite levels |
| Drinking water containing nitrate up to acceptable daily intake level (ADI = 3.7 mg/kg bw) in combination with 300 grams of processed meat, white meat or processed meat enriched with natural compounds3.7 mg nitrate/kg bw per day plus 300 grams of meat for 1 week | Dietary supplement | Normal nitrite levels, Reduced nitrite levels |
Primary outcome
Change in N-nitroso compound (NOC) levels in faeces and urine measured as apparent total nitroso compounds (ATNC) between baseline levels at the start of the intervention and each intervention period
Time frame: At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks
The faecal and urinal level of NOC is measured as Total Apparent Nitroso Compounds (ATNC) and used indicator of colonic endogenous nitrosation. It is known to significantly increase following strictly controlled diets high in red or processed meat.
Change in whole genome gene expression analyses in colonic biopsies and blood between baseline levels and each intervention period (transcriptomics)
Time frame: At baseline, at 2 weeks, at 4 weeks, and at 6 weeks
Colon biopsies and blood will be analysed for transcriptomic responses to the dietary changes. This will provide information on gene expression changes in the colon epithelium that may be linked with other parameters such as faecal NOC levels. This will also identify molecular pathways that can link dietary composition to processes involved in cancer development.
5 secondary outcomes
Change in urinary nitrate and creatine levels between baseline levels at the start of the intervention and each intervention period.
Time frame: At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks
Genotyping of DNA
Time frame: At baseline
Change in DNA methylation analyses of DNA isolated from colonic biopsies and blood (epigenetics) between baseline levels at the start of the intervention and each intervention period
Time frame: At baseline, at 2 weeks, at 4 weeks, at 6 weeks
Change in enzyme activity of nitrate reductase in saliva between baseline levels at the start of the intervention and each intervention period
Time frame: At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks
Change in the microbiome in feacal samples and in saliva between baseline levels at the start of the intervention and each intervention period
Time frame: At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2019.
- Background: PubMed 20004993de Oliveira CE, Stamford TL, Gomes Neto NJ, de Souza EL. Inhibition of Staphylococcus aureus in broth and meat broth using synergies of phenolics and organic acids. Int J Food Microbiol. 2010 Feb 28;137(2-3):312-6. doi: 10.1016/j.ijfoodmicro.2009.11.019. Epub 2009 Dec 3.
- Background: PubMed 15246235Burt S. Essential oils: their antibacterial properties and potential applications in foods--a review. Int J Food Microbiol. 2004 Aug 1;94(3):223-53. doi: 10.1016/j.ijfoodmicro.2004.03.022.
- Background: PubMed 17628877Cheng KW, Chen F, Wang M. Inhibitory activities of dietary phenolic compounds on heterocyclic amine formation in both chemical model system and beef patties. Mol Nutr Food Res. 2007 Aug;51(8):969-76. doi: 10.1002/mnfr.200700032.
- Background: PubMed 11159760Hughes R, Cross AJ, Pollock JR, Bingham S. Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation. Carcinogenesis. 2001 Jan;22(1):199-202. doi: 10.1093/carcin/22.1.199.
- Background: PubMed 17052997Lunn JC, Kuhnle G, Mai V, Frankenfeld C, Shuker DE, Glen RC, Goodman JM, Pollock JR, Bingham SA. The effect of haem in red and processed meat on the endogenous formation of N-nitroso compounds in the upper gastrointestinal tract. Carcinogenesis. 2007 Mar;28(3):685-90. doi: 10.1093/carcin/bgl192. Epub 2006 Oct 19.
- Background: PubMed 21527577Cross AJ, Major JM, Sinha R. Urinary biomarkers of meat consumption. Cancer Epidemiol Biomarkers Prev. 2011 Jun;20(6):1107-11. doi: 10.1158/1055-9965.EPI-11-0048. Epub 2011 Apr 28.
- Background: PubMed 1854628Hall CN, Badawi AF, O'Connor PJ, Saffhill R. The detection of alkylation damage in the DNA of human gastrointestinal tissues. Br J Cancer. 1991 Jul;64(1):59-63. doi: 10.1038/bjc.1991.239.
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- PHYTOME websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Processed meat product, White meat wash-out and Processed meat products enriched with natural compounds in people with Colon Cancer, run by Maastricht University at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in N-nitroso compound (NOC) levels in faeces and urine measured as apparent total nitroso compounds (ATNC) between baseline levels at the start of the intervention and each intervention period (time frame: At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04138654, which also lists 38 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2019.