Mercury--ToxicologyNCT04060212
Mercury Metabolism by Bacteria in Humans
A study testing Tuna fish and prebiotic in people with Mercury--Toxicology, run by University of Rochester at 1 site in United States.
Trial summary
The purpose of this study is to evaluate how the bacteria in your gut can improve the break-down and de-toxification of non-harmful levels of a naturally occurring form of mercury (methylmercury) that comes with eating fish. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Mercury--Toxicology
- What is being tested?
- Tuna fish and prebiotic
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2019to 31 Aug 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects must be 18-80 years in age.
- Subjects must be in good general health based on self-reported health status, with the exception of self-reported conditions listed in the exclusion criteria.
- Subject must be willing to comply with study procedures.
Who cannot join
- Known allergy to fish.
- Pregnant or lactating women.
- Use of hair dyes or chemical treatments within the prior month and/or intent to use such treatments during the two trial periods. (Hair treatment during the washout period up to one month prior to the second trial is acceptable).
- Known gastrointestinal or renal disorders.
- Subjects with diminished mental capacity.
- Use of antibiotics within two months leading up to the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Rochester Medical Center
Rochester, New York, 14642
About this study
Official title: Microbial Mechanisms of Methylmercury Metabolism in Humans
The purpose of this study is to evaluate how the bacteria in your gut can improve the break-down and de-toxification of non-harmful levels of a naturally occurring form of mercury (methylmercury) that comes with eating fish. This research could help scientists and doctors understand whether or not mercury in fish that we are likely to eat poses any concern for the health of people.
Read the detailed description
The overall objective of this study is to investigate the role of gut microbes in mediating how humans metabolize and excrete the environmental neurotoxicant methylmercury (MeHg). Exposure to MeHg through consumption of fish continues to pose a health risk for many populations globally. There remains considerable uncertainty in advising the public on mercury risks associated with fish consumption. A great deal of uncertainty stems from the fact that the MeHg metabolism and elimination rate is known to vary widely from individual to individual. This translates into the possibility that two individuals consuming the same amount of fish with the same frequency could, unknowingly, experience as much as 4-fold difference in accumulation of MeHg in their bodies. Thus, there is a need for greater understanding of the mechanisms of MeHg metabolism and elimination, as well as for development of tools to assess these characteristics in people. Our scientific premise is that symbiotic microbes in the human gut are required for the efficient biotransformation (demethylation) and excretion of toxic MeHg. In this prospective intervention study we will examine the variation in the rate at which MeHg is excreted, both between human subjects and within subjects over time, and relate it to the MeHg demethylation activity that is harbored in their respective gut microbes. Furthermore, through intervention with a prebiotic dietary supplement, we will induce a change in the gut microbial composition within the same individual and evaluate if slower of faster MeHg metabolism ensues. With these approaches we will obtain gut microbiome samples that correlate with faster or slower MeHg elimination kinetics. We then aim to identify specific genera and species of bacteria in the human gut responsible for MeHg metabolism. We will do this by feeding volunteers fish meals with documented trace levels of MeHg that are below any harmful level of exposure. We will subsequently measure kinetic rates of MeHg elimination via mass-spectrometry analysis of hair strands. We will also sample feces from the subjects as a source of the gut microbiota and as a medium to analyze the extent of MeHg metabolism (demethylation) that parallels its elimination. Study team members at Montana State University will directly examine the ability of the human gut microbiota to induce MeHg metabolizing activity in germ-free mice at rates that correspond with that seen in the human subject it was derived from. In parallel, we will use metagenomic sequence-informed strategies to bring isolated strains of the human gut bacteria to culture and subsequently interrogate their MeHg demethylating activity. We anticipate our results will lead to a clearer understanding of the microbial basis of human MeHg metabolism.
- Conditions
- Mercury--Toxicology
- Being tested
- Tuna fish, prebiotic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tuna fishOther
Six meals of tunafish (~200gms) will be consumed. Three meals will be consumed in a period of 14 days, and a subsequent 3 meals will be consumed within a 14 day period six month after the first 3 meals.
prebioticDietary supplement
Prebiotin brand prebiotic will be consumed at 8grms/day for a period of 75 days. The prebiotic administration will begin with the second grouping of 3 fish meals.
| Study group | Role | What they receive |
|---|---|---|
| All Participants | Experimental | All participant will eat 6 meals of tuna fish. All participants will take a prebiotic dietary supplement. Receives: Other: Tuna fish; Dietary Supplement: prebiotic |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mercury Elimination Rate Before Pre-biotic
Mercury elimination rate will be determined for each individual at the beginning of the study, prior to any prebiotic administration. This determination will take place over the first 75 days of the study, wherein the first three fish meals are consumed, a eliminaiton period follows and then hair is sampled and analyzed. Time-resolved levels of mercury will be determined by longitudinal analysis of single hair strands using mass spectrometry methods. The values will be used to calculate the mercury elimination rate for each individual. The average elimination rate across the cohort before prebiotic will be reported. This total analysis will require approximately 2.5 months.
Measured: 2.5 months
Mercury Elimination Rate After Pre-biotic
Mercury elimination rate will be determined for each individual after commencing prebiotic self-administration for a period of 75 days, contemporaneously with the second set of fish meal consumption. This will begin approximately 6 months after the finish of the first round of fish meals and elimination (i.e. approximately 8.5 months after the participant starts the study). This second round will last approximately 2.5 months. Time-resolved levels of mercury will be determined by longitudinal analysis of single hair strands using mass spectrometry methods. The values will be used to calculate the mercury elimination rate for each individual. The average elimination rate across the cohort after prebiotic, from approximately 8.5 to 11 months will be reported.
Measured: 11 months
Secondary outcomes (1)
Change in Mercury Metabolism Ratio
Mercury metabolism ratio, i.e. conversion of methylmercury to inorganic mercury, will be determined for each individual before and after prebiotic administration. The difference in average metabolism ratio across the cohort before and after prebiotic will be reported. Mercury elimination ratios will be measured in stool samples using mass spectrometry methods.
Measured: Baseline to 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2019
- Study start1 Oct 2019
- Primary completion31 May 2021
- Study completion31 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mercury--ToxicologyStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Environmental Health Sciences (NIEHS)
- Responsible party
- Principal investigator, Matthew Rand, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04060212
- Sponsor's protocol ID
- 3842
- Other IDs
- R01ES030940
- Status last verified
- Sep 2023
- First submitted
- 15 Aug 2019
- Last updated
- 4 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Coe GL, Krout IN, Munro-Ehrlich M, Beamish CR, Vorojeikina D, Colman DR, Boyd EJ, Walk ST, Rand MD. Assessing the role of the gut microbiome in methylmercury demethylation and elimination in humans and gnotobiotic mice. Arch Toxicol. 2023 Sep;97(9):2399-2418. doi: 10.1007/s00204-023-03548-7. Epub 2023 Jul 1.
PubMed 37392210
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microbial Mechanisms of Methylmercury Metabolism in Humans
- ClinicalTrials.gov ID
- NCT04060212
- Acronym / sponsor ID
- 3842
- Conditions
- Mercury--Toxicology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- National Institute of Environmental Health Sciences (NIEHS)
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 31 May 2021 (actual)
- Study completion
- 31 Aug 2023 (actual)
- First posted
- 19 Aug 2019 (actual)
- Results
- Posted 2 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate how the bacteria in your gut can improve the break-down and de-toxification of non-harmful levels of a naturally occurring form of mercury (methylmercury) that comes with eating fish. This research could help scientists and doctors understand whether or not mercury in fish that we are likely to eat poses any concern for the health of people.
Detailed description
The overall objective of this study is to investigate the role of gut microbes in mediating how humans metabolize and excrete the environmental neurotoxicant methylmercury (MeHg). Exposure to MeHg through consumption of fish continues to pose a health risk for many populations globally. There remains considerable uncertainty in advising the public on mercury risks associated with fish consumption. A great deal of uncertainty stems from the fact that the MeHg metabolism and elimination rate is known to vary widely from individual to individual. This translates into the possibility that two individuals consuming the same amount of fish with the same frequency could, unknowingly, experience as much as 4-fold difference in accumulation of MeHg in their bodies. Thus, there is a need for greater understanding of the mechanisms of MeHg metabolism and elimination, as well as for development of tools to assess these characteristics in people. Our scientific premise is that symbiotic microbes in the human gut are required for the efficient biotransformation (demethylation) and excretion of toxic MeHg. In this prospective intervention study we will examine the variation in the rate at which MeHg is excreted, both between human subjects and within subjects over time, and relate it to the MeHg demethylation activity that is harbored in their respective gut microbes. Furthermore, through intervention with a prebiotic dietary supplement, we will induce a change in the gut microbial composition within the same individual and evaluate if slower of faster MeHg metabolism ensues. With these approaches we will obtain gut microbiome samples that correlate with faster or slower MeHg elimination kinetics. We then aim to identify specific genera and species of bacteria in the human gut responsible for MeHg metabolism. We will do this by feeding volunteers fish meals with documented trace levels of MeHg that are below any harmful level of exposure. We will subsequently measure kinetic rates of MeHg elimination via mass-spectrometry analysis of hair strands. We will also sample feces from the subjects as a source of the gut microbiota and as a medium to analyze the extent of MeHg metabolism (demethylation) that parallels its elimination. Study team members at Montana State University will directly examine the ability of the human gut microbiota to induce MeHg metabolizing activity in germ-free mice at rates that correspond with that seen in the human subject it was derived from. In parallel, we will use metagenomic sequence-informed strategies to bring isolated strains of the human gut bacteria to culture and subsequently interrogate their MeHg demethylating activity. We anticipate our results will lead to a clearer understanding of the microbial basis of human MeHg metabolism.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Participants | Experimental | Other: Tuna fish, Dietary Supplement: prebioticAll participant will eat 6 meals of tuna fish. All participants will take a prebiotic dietary supplement. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subjects must be 18-80 years in age.
- Subjects must be in good general health based on self-reported health status, with the exception of self-reported conditions listed in the exclusion criteria.
- Subject must be willing to comply with study procedures.
Key exclusion criteria (6 listed)
- Known allergy to fish.
- Pregnant or lactating women.
- Use of hair dyes or chemical treatments within the prior month and/or intent to use such treatments during the two trial periods. (Hair treatment during the washout period up to one month prior to the second trial is acceptable).
- Known gastrointestinal or renal disorders.
- Subjects with diminished mental capacity.
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 |
|---|---|---|
| Tuna fishSix meals of tunafish (~200gms) will be consumed. Three meals will be consumed in a period of 14 days, and a subsequent 3 meals will be consumed within a 14 day period six month after the first 3 meals. | Other | All Participants |
| prebioticPrebiotin brand prebiotic will be consumed at 8grms/day for a period of 75 days. The prebiotic administration will begin with the second grouping of 3 fish meals. | Dietary supplement | All Participants |
Primary outcome
Mercury Elimination Rate Before Pre-biotic
Time frame: 2.5 months
Mercury elimination rate will be determined for each individual at the beginning of the study, prior to any prebiotic administration. This determination will take place over the first 75 days of the study, wherein the first three fish meals are consumed, a eliminaiton period follows and then hair is sampled and analyzed. Time-resolved levels of mercury will be determined by longitudinal analysis of single hair strands using mass spectrometry methods. The values will be used to calculate the mercury elimination rate for each individual. The average elimination rate across the cohort before prebiotic will be reported. This total analysis will require approximately 2.5 months.
Mercury Elimination Rate After Pre-biotic
Time frame: 11 months
Mercury elimination rate will be determined for each individual after commencing prebiotic self-administration for a period of 75 days, contemporaneously with the second set of fish meal consumption. This will begin approximately 6 months after the finish of the first round of fish meals and elimination (i.e. approximately 8.5 months after the participant starts the study). This second round will last approximately 2.5 months. Time-resolved levels of mercury will be determined by longitudinal analysis of single hair strands using mass spectrometry methods. The values will be used to calculate the mercury elimination rate for each individual. The average elimination rate across the cohort after prebiotic, from approximately 8.5 to 11 months will be reported.
1 secondary outcome
Change in Mercury Metabolism Ratio
Time frame: Baseline to 10 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37392210Coe GL, Krout IN, Munro-Ehrlich M, Beamish CR, Vorojeikina D, Colman DR, Boyd EJ, Walk ST, Rand MD. Assessing the role of the gut microbiome in methylmercury demethylation and elimination in humans and gnotobiotic mice. Arch Toxicol. 2023 Sep;97(9):2399-2418. doi: 10.1007/s00204-023-03548-7. Epub 2023 Jul 1.
- Individual participant dataSharing planned: Yes
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 Tuna fish and prebiotic in people with Mercury--Toxicology, run by University of Rochester at 1 site in United States.
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 3 inclusion and 6 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 4 Oct 2023. 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 United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mercury Elimination Rate Before Pre-biotic (time frame: 2.5 months). 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 NCT04060212, which also lists 1 linked publication.
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 4 Oct 2023.