Cardiovascular Risk FactorNCT04160481
A Pilot Study to Investigate the Effect of Water-soluble Tomato Extract on TMAO
A study testing FruitFlow in people with Cardiovascular Risk Factor, run by dsm-firmenich Switzerland AG at 1 site in Ireland.
Trial summary
To determine the effect of 4 weeks daily consumption of Fruitflow on changes in plasma levels of fasting Trimethylamine N-oxide concentrations (TMAO) Read more about this study
- Who is it for?
- Ages 35 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Risk Factor
- What is being tested?
- FruitFlow
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteIreland
- Study dates
- 12 Nov 2019to 13 Mar 2020
- Phase
- Interventional
- 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 35 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Be able to give written informed consent;
- Be between 35 and 65 years of age;
- Has a BMI between 28 - 35 Kg/m2;
- Has a stable body weight (≤5% change) over the past 3-months;
- Is in general good health, as determined by the investigator;
- Avoid consuming dietary supplements (prebiotic, probiotic, fibre, resveratrol, fish oil, seed oils, ginkgo biloba, ginseng, fruit powder extracts and DHA) within 4 weeks prior to baseline visit, until the end of the study;
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- Avoid consuming seafood or fish 24h prior to each visit;
- Maintain current level of physical activity;
- Willing to consume the investigational product daily for the duration of the study.
Who cannot join
- Pregnant or breastfeeding women; women planning to become pregnant during the study;
- Are hypersensitive to any of the components of the test product;
- Has taken antibiotics within the previous 3 months;
- Has taken hypolipidemic agents or any treatment for diabetes (type I or II) within the previous 6 months;
- Has a history of drug and/or alcohol abuse at the time of enrolment;
- Consumes greater than 2 servings/day of alcohol (e.g. >28 g ethanol/day);
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- Is a smoker;
- Has made any major dietary changes in the past 3 months;
- Planned major changes in life style (i.e. diet, dieting, exercise level, travelling) during the duration of the study;
- Has an eating disorder;
- Is vegetarian/vegan diet or has food allergies or other issues with foods that would preclude intake of the study products;
- Is using fibre supplements or enemas;
- Has any health conditions that would prevent from fulfilling the study requirements, put the subject at risk or would confound the interpretation of the study results as judged by the investigator on the basis of medical history and routine laboratory test results;
- Have a significant acute or chronic coexisting illness such as cardiovascular disease, chronic kidney or liver disease, gastrointestinal disorder, endocrinological disorder, immunological disorder, metabolic disease or any condition which contraindicates, in the investigator's judgement, entry to the study;
- Current hepatic failure, renal failure, bleeding disorder (haemophilia, Von Willebrand disease, oesophageal varicoses);
- Having a condition or taking a medication that the investigator believes would interfere with the objectives of the study, pose a safety risk or confound the interpretation of the study results; to include Statins (including atorvastatin (Lipitor and Torvast), fluvastatin (Lescol), lovastatin (Mevacor, Altocor, Altoprev), pitavastatin (Livalo, Pitava), pravastatin (Pravachol, Selektine, Lipostat), rosuvastatin (Crestor) and simvastatin (Zocor, Lipex)), Cholesterol Absorption Inhibitors (including Zetia (ezetimibe)), Niacin (nicotinic acid), Fibric acid derivatives (including Atromid-S (clofibrate), Lopid (gemfibrozil), and Tricor (fenofibrate)), Bile Acid Sequestrants (including cholestyramine, sold under the brand names Questran, Prevalite, and LoCholest, and colestipol (Colestid)) or have taken them in the past 28 days;
- Taking a cholesterol lowering supplement, including, example Plant sterols/stanols, Fish Oil supplements, vitamin B supplements (e.g. Niacin and Niacinamide), red rice yeast extract, oat beta glucan, pharmaceutical garlic or have taken them in the past month;
- Has an active gastrointestinal disorder or previous gastrointestinal surgery;
- If taking chronic medications (e.g., anti-hypertensive medications), they must have been taking the product for at least two months prior to screening and agree to maintain the same dosage throughout the study;
- Has a gastrointestinal or chronic infective disease (i.e., diarrhoea, Crohn's disease, ulcerative colitis, irritable bowel syndrome, diverticulosis, stomach or duodenal ulcers, hepatitis, HIV, cancer, etc.), with a history of such diseases;
- Are severely immunocompromised (HIV positive, transplant patient, on antirejection medications, on a steroid for >30 days, or chemotherapy or radiotherapy within the last year);
- Experiences alarm features such as weight loss, rectal bleeding, recent change in bowel habit (<3 months) or abdominal pain;
- Have a malignant disease or any concomitant end-stage organ disease;
- Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the trial;
- Subjects may not be receiving treatment involving experimental drugs. If the subject has been in a recent experimental trial, these must have been completed not less than 60 days prior to this study;
- High habitual intake of tomatoes, and tomato-based products confirmed by FFQ.
- Known history of allergies to tomatoes or tomato-based products;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Double-blinded, Cross-over, Placebo- Controlled Pilot Study to Investigate the Effect of Tomato Extract on TMAO in Overweight or Obese Adults
To determine the effect of 4 weeks daily consumption of Fruitflow on changes in plasma levels of fasting Trimethylamine N-oxide concentrations (TMAO)
Read the detailed description
Tomatoes contain a range of polyphenols that are of low bioavailability and reach the colon. Data from animal studies suggest that certain polyphenols are extensively metabolized by the gut microbiota which may impact bioactivity including TMA/TMAO production. It was previously shown that a polyphenol-rich cranberry extract attenuated diet-induced metabolic syndrome in mice in a gut microbiota-dependent manner. In another mouse study the polyphenol resveratrol attenuated TMAO-induced atherosclerosis by decreasing TMAO levels and increasing hepatic bile acid neosynthesis via gut microbiota remodelling. However, human studies on polyphenol effect on TMAO levels and the gut microbiome are sparse. In a recent study TMAO serum levels were reduced in healthy subjects upon supplementation with a grape pomace polyphenolic extract.
This clinical study will provide new insight into the effect of tomato extract on TMAO levels and the gut microbiota composition and thus potential new mechanisms responsible for the cardiovascular protective effects.
- Conditions
- Cardiovascular Risk Factor
- Being tested
- FruitFlow, Placebo
- Keywords
- gut microbiome, carciovascular risk factor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FruitFlowDietary supplement
300mg tomato extract
PlaceboDietary supplement
Maltodextrin
| Study group | Role | What they receive |
|---|---|---|
| Tomato extract | Active comparator | Not described Receives: Dietary Supplement: FruitFlow |
| Placebo | Placebo comparator | Not described Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in TMAO concentrations
Changes in plasma levels of fasting Trimethylamine N-oxide concentrations (TMAO) at baseline.
Measured: 4 weeks
Secondary outcomes (6)
Changes in the relative abundance of common human gut microbes in stool samples
Bifidobacterium sp. Blautia sp. Clostridium sp. Collinsella sp. Dorea sp. Eubacterium sp. Faecalibacterium prausnitziiLachnospira sp. Lactobacillus sp. Parabacteroides sp. Akkermansia Roseburia sp. Ruminococcus sp. Streptococcus sp. Bacillus sp. E. coli PseudomonasStaphylococcus sp. Bacteroides fragilis Salmonella sp. Shigella sp.Campylobacter sp. Yersinia sp
Measured: 4 weeks
Urinary TMAO
Changes in urine levels of fasting TMAO
Measured: 4 weeks
LPS
Changes in plasma levels of lipopolysaccharide (LPS)
Measured: 4 weeks
Stool consistency
Changes in stool consistency as determined by the Bristol Stool Scale Stool Chart (BSC)
Measured: 4 weeks
Stool microbiota composition alpha diversity
Changes in total (DNA) and active (RNA) microbiome in stool as measured by: Observed number of taxa, Shannon index of diversity, Chao I, ACE, Evenness
Measured: 4 weeks
Stool microbiota composition beta diversity
Global changes in standing and active microbial communities between baseline and end of treatment as measured by beta diversity indices (Bray-Curtis and Jaccard distances).
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2019
- Study start12 Nov 2019
- Primary completion13 Mar 2020
- Study completion13 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular Risk FactorStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, double-blind, placebo-controlled, cross-over
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- dsm-firmenich Switzerland AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04160481
- Sponsor's protocol ID
- 2018-08-07-RESV
- Status last verified
- Mar 2020
- First submitted
- 8 Nov 2019
- Last updated
- 26 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Miller CA, Corbin KD, da Costa KA, Zhang S, Zhao X, Galanko JA, Blevins T, Bennett BJ, O'Connor A, Zeisel SH. Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study. Am J Clin Nutr. 2014 Sep;100(3):778-86. doi: 10.3945/ajcn.114.087692. Epub 2014 Jun 18.
PubMed 24944063Annunziata G, Maisto M, Schisano C, Ciampaglia R, Narciso V, Tenore GC, Novellino E. Effects of Grape Pomace Polyphenolic Extract (Taurisolo(R)) in Reducing TMAO Serum Levels in Humans: Preliminary Results from a Randomized, Placebo-Controlled, Cross-Over Study. Nutrients. 2019 Jan 10;11(1):139. doi: 10.3390/nu11010139.
PubMed 30634687Bergeron N, Williams PT, Lamendella R, Faghihnia N, Grube A, Li X, Wang Z, Knight R, Jansson JK, Hazen SL, Krauss RM. Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a gut microbiome metabolite associated with CVD risk. Br J Nutr. 2016 Dec;116(12):2020-2029. doi: 10.1017/S0007114516004165. Epub 2016 Dec 20.
PubMed 27993177Cassidy A, Minihane AM. The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids. Am J Clin Nutr. 2017 Jan;105(1):10-22. doi: 10.3945/ajcn.116.136051. Epub 2016 Nov 23.
PubMed 27881391Cardona F, Andres-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuno MI. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem. 2013 Aug;24(8):1415-22. doi: 10.1016/j.jnutbio.2013.05.001.
PubMed 23849454Rehman A, Tyree SM, Fehlbaum S, DunnGalvin G, Panagos CG, Guy B, Patel S, Dinan TG, Duttaroy AK, Duss R, Steinert RE. A water-soluble tomato extract rich in secondary plant metabolites lowers trimethylamine-n-oxide and modulates gut microbiota: a randomized, double-blind, placebo-controlled cross-over study in overweight and obese adults. J Nutr. 2023 Jan;153(1):96-105. doi: 10.1016/j.tjnut.2022.11.009. Epub 2022 Dec 23.
PubMed 36913483
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blinded, Cross-over, Placebo- Controlled Pilot Study to Investigate the Effect of Tomato Extract on TMAO in Overweight or Obese Adults
- ClinicalTrials.gov ID
- NCT04160481
- Acronym / sponsor ID
- 2018-08-07-RESV
- Conditions
- Cardiovascular Risk Factor
- Keywords
- gut microbiome, carciovascular risk factor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- dsm-firmenich Switzerland AGIndustry (pharma, biotech, devices)
- Study start
- 12 Nov 2019 (actual)
- Primary completion
- 13 Mar 2020 (actual)
- Study completion
- 13 Mar 2020 (actual)
- First posted
- 13 Nov 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.
To determine the effect of 4 weeks daily consumption of Fruitflow on changes in plasma levels of fasting Trimethylamine N-oxide concentrations (TMAO)
Detailed description
Tomatoes contain a range of polyphenols that are of low bioavailability and reach the colon. Data from animal studies suggest that certain polyphenols are extensively metabolized by the gut microbiota which may impact bioactivity including TMA/TMAO production. It was previously shown that a polyphenol-rich cranberry extract attenuated diet-induced metabolic syndrome in mice in a gut microbiota-dependent manner. In another mouse study the polyphenol resveratrol attenuated TMAO-induced atherosclerosis by decreasing TMAO levels and increasing hepatic bile acid neosynthesis via gut microbiota remodelling. However, human studies on polyphenol effect on TMAO levels and the gut microbiome are sparse. In a recent study TMAO serum levels were reduced in healthy subjects upon supplementation with a grape pomace polyphenolic extract.
This clinical study will provide new insight into the effect of tomato extract on TMAO levels and the gut microbiota composition and thus potential new mechanisms responsible for the cardiovascular protective effects.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind, placebo-controlled, cross-over
| Arm | Type | Receives |
|---|---|---|
| Tomato extract | Active comparator | Dietary Supplement: FruitFlow |
| Placebo | Placebo comparator | Dietary Supplement: Placebo |
Who may qualify
- Ages
- 35 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Be able to give written informed consent;
- Be between 35 and 65 years of age;
- Has a BMI between 28 - 35 Kg/m2;
- Has a stable body weight (≤5% change) over the past 3-months;
- Is in general good health, as determined by the investigator;
Key exclusion criteria (27 listed)
- Pregnant or breastfeeding women; women planning to become pregnant during the study;
- Are hypersensitive to any of the components of the test product;
- Has taken antibiotics within the previous 3 months;
- Has taken hypolipidemic agents or any treatment for diabetes (type I or II) within the previous 6 months;
- Has a history of drug and/or alcohol abuse at the time of enrolment;
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 |
|---|---|---|
| FruitFlow300mg tomato extract | Dietary supplement | Tomato extract |
| PlaceboMaltodextrin | Dietary supplement | Placebo |
Primary outcome
Change in TMAO concentrations
Time frame: 4 weeks
Changes in plasma levels of fasting Trimethylamine N-oxide concentrations (TMAO) at baseline.
6 secondary outcomes
Changes in the relative abundance of common human gut microbes in stool samples
Time frame: 4 weeks
Urinary TMAO
Time frame: 4 weeks
LPS
Time frame: 4 weeks
Stool consistency
Time frame: 4 weeks
Stool microbiota composition alpha diversity
Time frame: 4 weeks
Stool microbiota composition beta diversity
Time frame: 4 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 26 Mar 2020.
- Background: PubMed 24944063Miller CA, Corbin KD, da Costa KA, Zhang S, Zhao X, Galanko JA, Blevins T, Bennett BJ, O'Connor A, Zeisel SH. Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study. Am J Clin Nutr. 2014 Sep;100(3):778-86. doi: 10.3945/ajcn.114.087692. Epub 2014 Jun 18.
- Background: PubMed 30634687Annunziata G, Maisto M, Schisano C, Ciampaglia R, Narciso V, Tenore GC, Novellino E. Effects of Grape Pomace Polyphenolic Extract (Taurisolo(R)) in Reducing TMAO Serum Levels in Humans: Preliminary Results from a Randomized, Placebo-Controlled, Cross-Over Study. Nutrients. 2019 Jan 10;11(1):139. doi: 10.3390/nu11010139.
- Background: PubMed 27993177Bergeron N, Williams PT, Lamendella R, Faghihnia N, Grube A, Li X, Wang Z, Knight R, Jansson JK, Hazen SL, Krauss RM. Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a gut microbiome metabolite associated with CVD risk. Br J Nutr. 2016 Dec;116(12):2020-2029. doi: 10.1017/S0007114516004165. Epub 2016 Dec 20.
- Background: PubMed 27881391Cassidy A, Minihane AM. The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids. Am J Clin Nutr. 2017 Jan;105(1):10-22. doi: 10.3945/ajcn.116.136051. Epub 2016 Nov 23.
- Background: PubMed 23849454Cardona F, Andres-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuno MI. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem. 2013 Aug;24(8):1415-22. doi: 10.1016/j.jnutbio.2013.05.001.
- Derived from this study: PubMed 36913483Rehman A, Tyree SM, Fehlbaum S, DunnGalvin G, Panagos CG, Guy B, Patel S, Dinan TG, Duttaroy AK, Duss R, Steinert RE. A water-soluble tomato extract rich in secondary plant metabolites lowers trimethylamine-n-oxide and modulates gut microbiota: a randomized, double-blind, placebo-controlled cross-over study in overweight and obese adults. J Nutr. 2023 Jan;153(1):96-105. doi: 10.1016/j.tjnut.2022.11.009. Epub 2022 Dec 23.
- 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 study testing FruitFlow in people with Cardiovascular Risk Factor, run by dsm-firmenich Switzerland AG at 1 site in Ireland.
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 9 inclusion and 27 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 26 Mar 2020. 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 Ireland. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 TMAO concentrations (time frame: 4 weeks). 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 NCT04160481, which also lists 6 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 26 Mar 2020.