Lung CancerProject 5NCT01158456
Metabolism of NNK Among African Americans
An observational study of Lung Cancer, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
Metabolism and DNA adduct formation are critical in cancer induction by NNK. The investigators goal is to understand whether the observed ethnic/racial differences in lung cancer incidence are due to variations in NNK metabolism. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Lung Cancer
- How many people
- 161 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to Nov 2017
- 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 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Subjects will be classified as African American if they report themselves, biological parents and both sets of biological grandparents as African American or African descent. Similar criteria will be applied to European Americans (e.g., self, both parents and four grandparents of European American or European descent). Subjects will be evenly divided by gender.
Who may be able to join
- Male or female subjects with a smoking history of at least 10 cigarettes daily for at least 1 year;
- Subjects report themselves, biological parents and both sets of biological grandparents as
- African American or African descent or
- European American or European descent
- Subjects are in apparently good physical health (no unstable medical condition)
- Subjects are in stable, good mental health (e.g. not currently, within the past 6 months, experiencing unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the PRIME-MD);
- Subjects have provided written informed consent to participate in the study.
Who cannot join
- Unstable medical conditions including cancer, coronary heart disease and arrhythmia
- Cannot or unwilling to identify ethnic/racial ancestry
- Women who are currently pregnant or breast feeding
- Currently using any other tobacco or nicotine-containing product
- Currently taking any medications that affect relevant metabolic enzymes.
Trial locations and contacts
1 site in 1 country.
United States1 site
Tobacco Research Programs University of Minnesota
Minneapolis, Minnesota, 55414
About this study
Official title: Mechanisms of Ethnic/Racial Differences in Lung Cancer Due to Cigarette Smoking: Project 5: Metabolism of NNK Among African Americans
Metabolism and DNA adduct formation are critical in cancer induction by NNK. The investigators goal is to understand whether the observed ethnic/racial differences in lung cancer incidence are due to variations in NNK metabolism. The investigators overall hypothesis is that cancer susceptibility relates to carcinogen dose and to the balance between carcinogen metabolic activation and detoxification. The investigators propose to test this hypothesis via investigation of potential differences in NNK metabolic activation and detoxification in African American and European American smokers.
Read the detailed description
Lung cancer is the most common cause of cancer death in the United States, with the annual number of cases estimated at 162,460 deaths per year. It is more prevalent in African Americans as compared to European Americans. Cigarette smoking causes up to 90% of lung cancer, being the major risk factor in both African Americans and European Americans.
Tobacco-specific nitrosamines (TSNA) are among the most significant carcinogens in tobacco products. Multiple international studies clearly document the occurrence of substantial amounts of these carcinogens in both unburned tobacco and tobacco smoke. One of the most prevalent of these compounds, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is present in both unburned tobacco and cigarette smoke, and is a remarkably effective lung carcinogen in laboratory animals, inducing lung tumors in rodents independent of the route of administration. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of NNK, is also a pulmonary carcinogen. NNK has been classified by the International Agency for Research on Cancer as a Group 1 carcinogen (carcinogenic to humans). Consistent with this, 2 recent studies by our group have demonstrated that levels of NNAL in serum or urine are related to lung cancer in smokers.
Our primary aim is to conduct a comprehensive analysis of urinary biomarkers of NNK metabolic activation and detoxification in African American and European American smokers. We hypothesize that, after adjustment for smoking level, the relative contribution of the biomarkers of NNK metabolic activation to the total amount of NNK metabolites will be higher in African Americans as compared to European Americans. Our secondary aim is to measure in exfoliated oral mucosa cells of African American and European American smokers DNA adducts formed as a result of NNK metabolic activation. The results of these measurements will offer a direct measure of NNK-induced DNA damage in smokers, and will be critical to an understanding of the balance between the urinary excretion of NNK metabolites and the extent of NNK DNA binding. We hypothesize that African Americans will have in the DNA of their oral mucosa cells higher levels of NNK-derived DNA adducts as compared to European Americans. Finally, we will investigate the relationship between levels of NNK-derived DNA adducts measured in oral mucosa cells and the rates of repair of these adducts in cultured lymphocytes from our subjects. These measurements will allow us to evaluate more fully the role of variations in NNK metabolism in the observed differences in lung cancer risk between European American and African American smokers. We expect that that African Americans will have lower capacity to repair NNK-induced DNA damage as compared to European Americans, and this will correlate with higher levels of NNK-derived buccal DNA adducts.
- Conditions
- Lung Cancer
- Keywords
- smoking, lung cancer, ethnic racial differences, tobacco specific nitrosamines, metabolism of carcinogens
- Medical subject headings
- Lung Neoplasms, Smoking
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 |
|---|---|---|
| African Americans | Subjects will be classified as African American if they report themselves, biological parents and both sets of biological grandparents as African American or African descent. | |
| European American | Subjects will be classified as European American if they report themselves, biological parents and both sets of biological grandparents as European American or European descent. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conduct a comprehensive analysis of urinary biomarkers of NNK metabolic activation and detoxification in African American and European American smokers.
We will recruit smokers to smoke specially prepared cigarettes containing [pyridine-D4]NNK, and measure deuterium-labeled NNK metabolites in the urine of these subjects. The rationale for the use of deuterium-labeled NNK is that we need to specifically identify NNK-derived metabolites, because these biomarkers are also formed as a result of nicotine metabolism. Our overall hypothesis is that the relative contribution of the biomarkers of NNK metabolic activation to the total amount of NNK metabolites will be higher in African Americans as compared to European Americans.
Measured: 10 days
Secondary outcomes (2)
Measure in exfoliated oral mucosa cells of African American and European American smokers DNA adducts formed as a result of NNK metabolic activation.
We will collect exfoliated oral mucosa cell samples from the recruited subjects. DNA isolated from these samples will be analyzed for [pyridine-D4]NNK-derived adducts. Our overall hypothesis in this Specific Aim is that African Americans will have in the DNA of their oral mucosa cells higher levels of NNK-derived DNA adducts as compared to European Americans.
Measured: 10 days
Assess the repair of NNK-induced DNA damage.
We will investigate the relationship between the levels of NNK-derived DNA adducts measured in the oral mucosa cells and the rates of repair of these adducts in cultured lymphocytes from our subjects. Our overall hypothesis for this Specific Aim is that African Americans will have lower capacity to repair NNK-induced DNA damage as compared to European Americans, and this will correlate with higher levels of [pyridine-D4]NNK-derived buccal DNA adducts.
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2010 (estimated)
- Study startDec 2010
- Primary completionSep 2014
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 161 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Dorothy K Hatsukami, Ph.D., Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01158456
- Sponsor's protocol ID
- 2010NTLS056
- Other IDs
- 1P01CA138338-01A1
- Acronym
- Project 5
- Status last verified
- Apr 2023
- First submitted
- 6 Jul 2010
- Last updated
- 10 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Ethnic/Racial Differences in Lung Cancer Due to Cigarette Smoking: Project 5: Metabolism of NNK Among African Americans
- ClinicalTrials.gov ID
- NCT01158456
- Acronym / sponsor ID
- Project 5 / 2010NTLS056
- Conditions
- Lung Cancer
- Keywords
- smoking, lung cancer, ethnic racial differences, tobacco specific nitrosamines, metabolism of carcinogens
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 161 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2010
- Primary completion
- Sep 2014 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 8 Jul 2010 (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.
Metabolism and DNA adduct formation are critical in cancer induction by NNK. The investigators goal is to understand whether the observed ethnic/racial differences in lung cancer incidence are due to variations in NNK metabolism. The investigators overall hypothesis is that cancer susceptibility relates to carcinogen dose and to the balance between carcinogen metabolic activation and detoxification. The investigators propose to test this hypothesis via investigation of potential differences in NNK metabolic activation and detoxification in African American and European American smokers.
Detailed description
Lung cancer is the most common cause of cancer death in the United States, with the annual number of cases estimated at 162,460 deaths per year. It is more prevalent in African Americans as compared to European Americans. Cigarette smoking causes up to 90% of lung cancer, being the major risk factor in both African Americans and European Americans.
Tobacco-specific nitrosamines (TSNA) are among the most significant carcinogens in tobacco products. Multiple international studies clearly document the occurrence of substantial amounts of these carcinogens in both unburned tobacco and tobacco smoke. One of the most prevalent of these compounds, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is present in both unburned tobacco and cigarette smoke, and is a remarkably effective lung carcinogen in laboratory animals, inducing lung tumors in rodents independent of the route of administration. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of NNK, is also a pulmonary carcinogen. NNK has been classified by the International Agency for Research on Cancer as a Group 1 carcinogen (carcinogenic to humans). Consistent with this, 2 recent studies by our group have demonstrated that levels of NNAL in serum or urine are related to lung cancer in smokers.
Our primary aim is to conduct a comprehensive analysis of urinary biomarkers of NNK metabolic activation and detoxification in African American and European American smokers. We hypothesize that, after adjustment for smoking level, the relative contribution of the biomarkers of NNK metabolic activation to the total amount of NNK metabolites will be higher in African Americans as compared to European Americans. Our secondary aim is to measure in exfoliated oral mucosa cells of African American and European American smokers DNA adducts formed as a result of NNK metabolic activation. The results of these measurements will offer a direct measure of NNK-induced DNA damage in smokers, and will be critical to an understanding of the balance between the urinary excretion of NNK metabolites and the extent of NNK DNA binding. We hypothesize that African Americans will have in the DNA of their oral mucosa cells higher levels of NNK-derived DNA adducts as compared to European Americans. Finally, we will investigate the relationship between levels of NNK-derived DNA adducts measured in oral mucosa cells and the rates of repair of these adducts in cultured lymphocytes from our subjects. These measurements will allow us to evaluate more fully the role of variations in NNK metabolism in the observed differences in lung cancer risk between European American and African American smokers. We expect that that African Americans will have lower capacity to repair NNK-induced DNA damage as compared to European Americans, and this will correlate with higher levels of NNK-derived buccal DNA adducts.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| African Americans | – | –Subjects will be classified as African American if they report themselves, biological parents and both sets of biological grandparents as African American or African descent. |
| European American | – | –Subjects will be classified as European American if they report themselves, biological parents and both sets of biological grandparents as European American or European descent. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects will be classified as African American if they report themselves, biological parents and both sets of biological grandparents as African American or African descent. Similar criteria will be applied to European Americans (e.g., self, both parents and four grandparents of European American or European descent). Subjects will be evenly divided by gender.
Key inclusion criteria (7 listed)
- Male or female subjects with a smoking history of at least 10 cigarettes daily for at least 1 year;
- Subjects report themselves, biological parents and both sets of biological grandparents as
- Subjects are in apparently good physical health (no unstable medical condition)
- Subjects are in stable, good mental health (e.g. not currently, within the past 6 months, experiencing unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the PRIME-MD);
- Subjects have provided written informed consent to participate in the study.
Key exclusion criteria (5 listed)
- Unstable medical conditions including cancer, coronary heart disease and arrhythmia
- Cannot or unwilling to identify ethnic/racial ancestry
- Women who are currently pregnant or breast feeding
- Currently using any other tobacco or nicotine-containing product
- Currently taking any medications that affect relevant metabolic enzymes.
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
Conduct a comprehensive analysis of urinary biomarkers of NNK metabolic activation and detoxification in African American and European American smokers.
Time frame: 10 days
We will recruit smokers to smoke specially prepared cigarettes containing [pyridine-D4]NNK, and measure deuterium-labeled NNK metabolites in the urine of these subjects. The rationale for the use of deuterium-labeled NNK is that we need to specifically identify NNK-derived metabolites, because these biomarkers are also formed as a result of nicotine metabolism. Our overall hypothesis is that the relative contribution of the biomarkers of NNK metabolic activation to the total amount of NNK metabolites will be higher in African Americans as compared to European Americans.
2 secondary outcomes
Measure in exfoliated oral mucosa cells of African American and European American smokers DNA adducts formed as a result of NNK metabolic activation.
Time frame: 10 days
Assess the repair of NNK-induced DNA damage.
Time frame: 10 days
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 10 Apr 2023.
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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.
Dorothy K Hatsukami, Ph.D. principal investigator
University of Minnesota
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 Lung Cancer, run by Masonic Cancer Center, University of Minnesota 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 7 inclusion and 5 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 10 Apr 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?
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?
Conduct a comprehensive analysis of urinary biomarkers of NNK metabolic activation and detoxification in African American and European American smokers. (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Apr 2023.