Normal PhysiologyNCT00340535
Effect of Genetic Differences on Levels of Water Disinfection Byproducts in Blood After Showering
An observational study of Normal Physiology, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study will examine whether genetic differences among individuals affect blood levels of certain chemicals called DBPs after showering. Chemicals such as chlorine and ozone are used to kill germs in water. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Normal Physiology
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jun 2004to 4 Mar 2021
- Phase
- Observational
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: convenience sample of individuals recruited at the University of Pittsburgh.
Who may be able to join
- The study population will be comprised of non-smoking males and females in the age range 18-45 years. The age range was selected to limit variability in activity of important enzyme systems.
- EXCLUSIONS CRITERIA:
- Persons with lung conditions will be excluded because inhalation is a major route of exposure for trihalomethanes.
- Liver conditions will be excluded because of the potential risks possibly associated with chlorzoxazone administration.
- Pregnant and lactating women will be excluded from participation in the study, for multiple reasons, the major one being possible (but unknown) adverse health risks from chlorzoxazone exposure.
- In addition, we will exclude persons with chronic conditions such as diabetes who chronically use medication, such as Orinase or others. These persons will be excluded due to unknown effects of such disease on the enzyme systems under investigation and to avoid any possible adverse effects of the study, including chlorzoxazone administration.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
About this study
Official title: Levels of Selected Potentially Carcinogenic Drinking Water Disinfection Byproducts in Whole Blood After Showering
This study will examine whether genetic differences among individuals affect blood levels of certain chemicals called DBPs after showering. Chemicals such as chlorine and ozone are used to kill germs in water. These chemicals may react with organic matter in the water and form other chemicals called disinfection byproducts, or DBPs. Although people are usually exposed to DBPs by drinking tap water, these chemicals may also penetrate the body during showering. This study will see whether the levels of DBPs after showering vary among individuals depending on differences in genes that code for enzymes called GSTT1, CYP2D6, and CYP2E1, which break down DBPs. This study, sponsored by the Centers for Disease Control and Prevention and the National Institutes of Health, is conducted at the University of Pittsburgh's Center for Clinical Pharmacology.
Healthy adults between 18 and 45 years of age who do not smoke cigarettes and are not taking any medicines may be eligible for this study. Candidates are screened with a medical history and blood and urine tests. Participants are given a diary to record the foods they eat and how much water they drink during the 2 days before their study appointment. The following activities are scheduled on the appointment day:
Read more
- Measurements of blood pressure, height, and weight, and pregnancy test for women
- Questions about alcohol consumed and medications taken in the last 48 hours
- Review of food and water diary
- Interview for demographic information (name, address, date of birth, etc.) and other information, such as sex, height, weight. Subjects are also asked about anything, such as exercise, that might affect their breathing, since breathing problems are a rare side effect of chlorzoxazone, a drug used in this study.
- Urine sample collection
- Blood draw and insertion of a small catheter (plastic tube) to allow for additional blood draws during the test procedure without having repeated needle sticks
- 10-minute shower in a private bathroom
- Blood sample collection 10 minutes after the shower and again at 30 minutes after the shower
- Dose of chlorzoxazone (a drug used to treat muscle pain)
- Interview about subject's exposure to water
- Light breakfast
- Blood and urine collections 2 hours after the chlorzoxazone dose
- Lunch
- Observation for drug side effects for 2 hours, or longer if needed
Seven blood samples totaling 75 milliliters (about 5 tablespoonfuls) of blood are collected during this study. The blood is tested for chemicals called trihalomethanes to see how they are broken down. The urine samples are tested for chemicals called haloacetic acids, which are found in tap water after it has been treated with chlorine.
Read the detailed description
Disinfection byproducts in drinking water (DBP) are inadvertently created when chlorine interacts with organic compounds in the untreated water. DBP have been implicated in elevated risk of several types of cancer. Until recently, ingestion was considered to be the major route of exposure. However, an NCI collaborative study in Spain is now showing a link between bladder cancer and exposure to DBP in water during showering or bathing. However, little is known of the mechanisms of action. Almost all drinking water disinfected with chlorine contains measurable levels of DBP. The DBP found in greatest concentration are the trihalomethanes [(THM); chloroform, bromoform, bromodichloromethane, and dibromochloromethane]. Previously, our collaborators from the CDC measured changes in blood THM levels after showering and bathing, and ingesting water. Showering resulted in the largest increases, with a wide range in the increase among subjects with similar exposures. Enzyme variants due to genetic polymorphisms may be responsible for these differences.
We plan to assess the association between the presence of enzyme variants (genetic polymorphisms) and the increase of trihalomethanes in the blood of people exposed to DBP while showering. The study will be conducted at the General Clinical Research Center (GCRC), Center for Clinical Pharmacology (CCP), University of Pittsburgh, Dr. Robert Branch, Director. Approximately 250 volunteers will be identified from Dr. Branch's ongoing research program. These subjects will have been pre-screened with a normal standard blood panel and for genetic polymorphisms of interest. From this pool of pre-screened individuals, we will recruit approximately 100 people who have enzyme variants of differing activity.
We will ask the 100 volunteers to provide seven 10-mL blood samples and two urine samples, and take a 10-minute shower at the study site (the CCP in Pittsburgh, PA). Blood samples will be analyzed for trihalomethane concentrations, and red blood cell enzyme activities. To study the activity of the enzyme CYP2E1, we will administer a single dose of chlorzoxazone, a muscle relaxant metabolized by this enzyme. We will measure enzyme activity by analyzing blood samples collected 2 hours post-administration. We will conduct a brief interview with each volunteer to obtain demographic and other information that might impact the dose of THM. We will collect ambient air samples before, during and after showering for each participant and analyze them for levels of THMs. A water sample will be collected during showering and analyzed for levels of THM and haloacetic acids. We will ask 10 randomly selected study subjects to repeat study activities for quality control purposes.
Levels of THM in blood before and after showering, and the rate of decrease in blood concentration, will be analyzed with respect to the presence of genetic polymorphisms for selected enzymes, or their phenotypic activity. Blood THM levels will also be compared with various demographic and physiologic measurements. To test intra-individual variation in several measures, ten randomly selected participants (stratified by sex, i.e. 5 males and 5 females) will be asked to conduct the study twice, with the two study appointments separated by at least a week.
- Conditions
- Normal Physiology
- Keywords
- Disinfection byproducts, Genetic Variation, Trihalomethanes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Individuals | Individuals recruited at U of Pittsburgh |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood trihalomethane levels
Levels of triahlomethane levels in the blood
Measured: Before and after showering
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start23 Jun 2004
- Primary completion1 Oct 2004
- Study completion4 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Normal PhysiologyStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Laura Beane-Freeman, Ph.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00340535
- Sponsor's protocol ID
- 999904228
- Other IDs
- 04-C-N228
- Status last verified
- Mar 2021
- First submitted
- 19 Jun 2006
- Last updated
- 5 Mar 2021
- Results posted
- No
Publications
Boorman GA. Drinking water disinfection byproducts: review and approach to toxicity evaluation. Environ Health Perspect. 1999 Feb;107 Suppl 1(Suppl 1):207-17. doi: 10.1289/ehp.99107s1207.
PubMed 10229719Cantor KP, Hoover R, Hartge P, Mason TJ, Silverman DT, Altman R, Austin DF, Child MA, Key CR, Marrett LD, et al. Bladder cancer, drinking water source, and tap water consumption: a case-control study. J Natl Cancer Inst. 1987 Dec;79(6):1269-79.
PubMed 3480378McGeehin MA, Reif JS, Becher JC, Mangione EJ. Case-control study of bladder cancer and water disinfection methods in Colorado. Am J Epidemiol. 1993 Oct 1;138(7):492-501. doi: 10.1093/oxfordjournals.aje.a116883.
PubMed 8213753
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levels of Selected Potentially Carcinogenic Drinking Water Disinfection Byproducts in Whole Blood After Showering
- ClinicalTrials.gov ID
- NCT00340535
- Acronym / sponsor ID
- 999904228
- Conditions
- Normal Physiology
- Keywords
- Disinfection byproducts, Genetic Variation, Trihalomethanes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 23 Jun 2004 (actual)
- Primary completion
- 1 Oct 2004 (actual)
- Study completion
- 4 Mar 2021 (actual)
- First posted
- 21 Jun 2006 (estimated)
- 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.
This study will examine whether genetic differences among individuals affect blood levels of certain chemicals called DBPs after showering. Chemicals such as chlorine and ozone are used to kill germs in water. These chemicals may react with organic matter in the water and form other chemicals called disinfection byproducts, or DBPs. Although people are usually exposed to DBPs by drinking tap water, these chemicals may also penetrate the body during showering. This study will see whether the levels of DBPs after showering vary among individuals depending on differences in genes that code for enzymes called GSTT1, CYP2D6, and CYP2E1, which break down DBPs. This study, sponsored by the Centers for Disease Control and Prevention and the National Institutes of Health, is conducted at the University of Pittsburgh's Center for Clinical Pharmacology.
Healthy adults between 18 and 45 years of age who do not smoke cigarettes and are not taking any medicines may be eligible for this study. Candidates are screened with a medical history and blood and urine tests. Participants are given a diary to record the foods they eat and how much water they drink during the 2 days before their study appointment. The following activities are scheduled on the appointment day:
- Measurements of blood pressure, height, and weight, and pregnancy test for women
- Questions about alcohol consumed and medications taken in the last 48 hours
- Review of food and water diary
- Interview for demographic information (name, address, date of birth, etc.) and other information, such as sex, height, weight. Subjects are also asked about anything, such as exercise, that might affect their breathing, since breathing problems are a rare side effect of chlorzoxazone, a drug used in this study.
- Urine sample collection
- Blood draw and insertion of a small catheter (plastic tube) to allow for additional blood draws during the test procedure without having repeated needle sticks
- 10-minute shower in a private bathroom
- Blood sample collection 10 minutes after the shower and again at 30 minutes after the shower
- Dose of chlorzoxazone (a drug used to treat muscle pain)
- Interview about subject's exposure to water
- Light breakfast
- Blood and urine collections 2 hours after the chlorzoxazone dose
- Lunch
- Observation for drug side effects for 2 hours, or longer if needed
Seven blood samples totaling 75 milliliters (about 5 tablespoonfuls) of blood are collected during this study. The blood is tested for chemicals called trihalomethanes to see how they are broken down. The urine samples are tested for chemicals called haloacetic acids, which are found in tap water after it has been treated with chlorine.
Detailed description
Disinfection byproducts in drinking water (DBP) are inadvertently created when chlorine interacts with organic compounds in the untreated water. DBP have been implicated in elevated risk of several types of cancer. Until recently, ingestion was considered to be the major route of exposure. However, an NCI collaborative study in Spain is now showing a link between bladder cancer and exposure to DBP in water during showering or bathing. However, little is known of the mechanisms of action. Almost all drinking water disinfected with chlorine contains measurable levels of DBP. The DBP found in greatest concentration are the trihalomethanes [(THM); chloroform, bromoform, bromodichloromethane, and dibromochloromethane]. Previously, our collaborators from the CDC measured changes in blood THM levels after showering and bathing, and ingesting water. Showering resulted in the largest increases, with a wide range in the increase among subjects with similar exposures. Enzyme variants due to genetic polymorphisms may be responsible for these differences.
We plan to assess the association between the presence of enzyme variants (genetic polymorphisms) and the increase of trihalomethanes in the blood of people exposed to DBP while showering. The study will be conducted at the General Clinical Research Center (GCRC), Center for Clinical Pharmacology (CCP), University of Pittsburgh, Dr. Robert Branch, Director. Approximately 250 volunteers will be identified from Dr. Branch's ongoing research program. These subjects will have been pre-screened with a normal standard blood panel and for genetic polymorphisms of interest. From this pool of pre-screened individuals, we will recruit approximately 100 people who have enzyme variants of differing activity.
We will ask the 100 volunteers to provide seven 10-mL blood samples and two urine samples, and take a 10-minute shower at the study site (the CCP in Pittsburgh, PA). Blood samples will be analyzed for trihalomethane concentrations, and red blood cell enzyme activities. To study the activity of the enzyme CYP2E1, we will administer a single dose of chlorzoxazone, a muscle relaxant metabolized by this enzyme. We will measure enzyme activity by analyzing blood samples collected 2 hours post-administration. We will conduct a brief interview with each volunteer to obtain demographic and other information that might impact the dose of THM. We will collect ambient air samples before, during and after showering for each participant and analyze them for levels of THMs. A water sample will be collected during showering and analyzed for levels of THM and haloacetic acids. We will ask 10 randomly selected study subjects to repeat study activities for quality control purposes.
Levels of THM in blood before and after showering, and the rate of decrease in blood concentration, will be analyzed with respect to the presence of genetic polymorphisms for selected enzymes, or their phenotypic activity. Blood THM levels will also be compared with various demographic and physiologic measurements. To test intra-individual variation in several measures, ten randomly selected participants (stratified by sex, i.e. 5 males and 5 females) will be asked to conduct the study twice, with the two study appointments separated by at least a week.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Individuals | – | –Individuals recruited at U of Pittsburgh |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- convenience sample of individuals recruited at the University of Pittsburgh.
Key inclusion criteria (6 listed)
- The study population will be comprised of non-smoking males and females in the age range 18-45 years. The age range was selected to limit variability in activity of important enzyme systems.
- Persons with lung conditions will be excluded because inhalation is a major route of exposure for trihalomethanes.
- Liver conditions will be excluded because of the potential risks possibly associated with chlorzoxazone administration.
- Pregnant and lactating women will be excluded from participation in the study, for multiple reasons, the major one being possible (but unknown) adverse health risks from chlorzoxazone exposure.
- In addition, we will exclude persons with chronic conditions such as diabetes who chronically use medication, such as Orinase or others. These persons will be excluded due to unknown effects of such disease on the enzyme systems under investigation and to avoid any possible adverse effects of the study, including chlorzoxazone administration.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Blood trihalomethane levels
Time frame: Before and after showering
Levels of triahlomethane levels in the blood
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 5 Mar 2021.
- Background: PubMed 10229719Boorman GA. Drinking water disinfection byproducts: review and approach to toxicity evaluation. Environ Health Perspect. 1999 Feb;107 Suppl 1(Suppl 1):207-17. doi: 10.1289/ehp.99107s1207.
- Background: PubMed 3480378Cantor KP, Hoover R, Hartge P, Mason TJ, Silverman DT, Altman R, Austin DF, Child MA, Key CR, Marrett LD, et al. Bladder cancer, drinking water source, and tap water consumption: a case-control study. J Natl Cancer Inst. 1987 Dec;79(6):1269-79.
- Background: PubMed 8213753McGeehin MA, Reif JS, Becher JC, Mangione EJ. Case-control study of bladder cancer and water disinfection methods in Colorado. Am J Epidemiol. 1993 Oct 1;138(7):492-501. doi: 10.1093/oxfordjournals.aje.a116883.
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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.
Laura Beane-Freeman, Ph.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Normal Physiology, run by National Cancer Institute (NCI) 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 6 inclusion and 0 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 5 Mar 2021. 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?
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?
Blood trihalomethane levels (time frame: Before and after showering). 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 NCT00340535, which also lists 3 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 5 Mar 2021.