- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05864352
The Role of Dietary Titanium Dioxide on the Human Gut Microbiome and Health
Study Overview
Status
Conditions
Detailed Description
The U.S. food supply contains large amounts of the food additive titanium dioxide (TiO2), but its impact on human health is unknown. The widespread use of food-grade TiO2 (E171) includes commonly consumed products, such as sweets, gums, white salad dressings, dairy creamers, pharmaceutical fillers, and toothpaste. Production of TiO2 in the U.S. is expected to increase more than 8.9% from 2016 to 2025. There are major limitations with current estimations of dietary TiO2 intake in humans. Such limitations include assessing TiO2 content solely from white-colored foods and including only foods with TiO¬2 labeled as such on its packaging. Natural food products, however, may also contribute a substantial amount of TiO¬2 to the diet. There is also a large variation in the estimated ingestion of TiO2 between studies which is likely due to differences in populations and varying food supplies, variability in analytical method used for measuring TiO2, and absence of validated dietary estimation tools to measure oral TiO2 exposure. Therefore, estimation of TiO¬2 dietary intake and gut exposure is needed among a free-living U.S. population of adults with a wide variation of intakes.
Pre-clinical models show that greater TiO2 oral exposure may lead to impaired gut health through changes in gut bacterial content and function. TiO2 has been shown to damage intestinal cells where small doses of TiO2 caused changes in normal activity, but not damage to the cell's genetics. After very small particles of TiO2 are taken up by these intestinal cells, it causes mild toxicity and disruption of the cell's function. In addition, very small particles of TiO2 accumulate in intestinal cells and remodel the cell's community in the small intestine, suggesting these particles may get absorbed into the body's blood and general circulation. These results demonstrate that very small particles of TiO2 causes harmful changes to the intestinal cells, is absorbed by the intestinal cells, and once inside, can cause harmfulness and promote abnormal cellular function. There is an urgent need for studies in humans to determine whether high versus low level exposure to TiO¬2 is related to gut inflammation and disruption in gut function.
The current study will fill these research gaps by testing the hypothesis that long term dietary exposure of TiO2 is related to gut inflammation and disturbs gut bacteria in humans. This hypothesis will be tested for the first time via these specific aims: 1) to quantify dietary TiO2 exposure by estimating dietary intake and measuring the fecal output of TiO2 in 80 adults; 2) to establish the relationship of dietary TiO2 with gut bacteria and their activity; and 3) to determine whether dietary TiO2 exposure is related to gut inflammation and associated inflammatory pathways.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
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Massachusetts
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Lowell, Massachusetts, United States, 01854
- University of Massachusetts
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Healthy persons between the ages of 18 to 30 y.
Exclusion Criteria:
- <18 years and >30 years
- antibiotic use in the past 6 months
- laxative use in the past 30 days
- self-reported fever, cancer, or gastrointestinal disease (e.g., inflammatory bowel diseases, C. difficile infection
- use of selective serotonin reuptake inhibitors (SSRI's)
- use of non-steroidal anti-inflammatory drugs (NSAIDs) within 10 days
- daily use of proton pump inhibitors
- history of gastrointestinal alteration (e.g., appendectomy, gastric bypass surgery)
- pregnancy.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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High TiO2 Consumer
Participants with an estimated TiO2 stool content greater than the cohort median content, μg/mg dry stool.
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Low TiO2 Consumer
Participants with an estimated TiO2 stool content less than the cohort median content, μg/mg dry stool.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Gut microbiota taxonomy and expressed pathways
Time Frame: During the study week, three consecutive day period.
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To evaluate the phylogeny and taxonomy of the gut microbiota in each of the three fecal samples per participant, fecal DNA and RNA will be isolated and purified and subject to Illumina-tag PCT to amplify 16S rRNA genes.
Samples will be subject to metatranscriptomics sequencing to compare microbial community level expression signatures associated with fecal TiO2.
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During the study week, three consecutive day period.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Concentration of Intestinal Inflammation Biomarkers in Feces
Time Frame: During the study week, three consecutive day period.
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To evaluate intestinal inflammation, the concentrations of fecal calprotectin, lactoferrin, and myeloperoxidase will be measured in stool using Immundiagnostik ELISA kits.
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During the study week, three consecutive day period.
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Concentration of Intestinal Homeostasis and Permeability Biomarkers in Feces
Time Frame: During the study week, three consecutive day period.
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To evaluate intestinal homeostasis and permeability, the concentrations of fecal α-1-antitrypsin (AAT) and zonulin will be measured in stool using Immundiagnostik ELISA kits.
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During the study week, three consecutive day period.
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Concentration of Intestinal Oxidative Stress Biomarkers in Feces
Time Frame: During the study week, three consecutive day period.
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To evaluate intestinal oxidative stress, the concentrations of leukotriene D4 (LD4) and 3-nitrotyrosine (3-NT) will be measured by liquid chromatography electron spray ionization tandem mass spectrometry (LC-ESIMS/MS).
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During the study week, three consecutive day period.
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Collaborators and Investigators
Investigators
- Principal Investigator: Kelsey M Mangano, PhD, University of Massachusetts, Lowell
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 21-122-MAN-XPD
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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