Tobacco Toxicant ExposurePhase 1NCT02414477
Metabolism of Deuterated NNN in Smokeless Tobacco Users
A Phase 1 study testing Deuterated NNN in people with Tobacco Toxicant Exposure, run by University of Minnesota at 1 site in United States.
Trial summary
The purpose of this study is to better understand how people break down a tobacco specific cancer-causing toxin called N'-nitrosonornicotine (NNN) that is present in smokeless tobacco and cigarettes. Some people are able to get rid of this chemical as a harmless agent better than others. Read more about this study
- Who is it for?
- Ages 21 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Tobacco Toxicant Exposure
- What is being tested?
- Deuterated NNN
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Apr 2018to 21 Feb 2020
- Phase
- Phase 1
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Regular smokeless tobacco user
- Good physical health with no unstable medical conditions
- Stable and good mental health, i.e., currently do not experience unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the DSM-IV criteria, during the past six months
- Willing to perform study activities such as having blood sample drawn, saliva collection, urine collection, multiple clinic visits
- For female subjects of child bearing potential, not known to be pregnant or nursing, or planning to become pregnant within next 12 months
- Provide written informed consent
Who cannot join
- Using other tobacco or nicotine containing products
- Unstable medical condition
- Currently taking any medications that affect relevant metabolic enzymes
- Not willing to use switch smokeless tobacco brand to use tobacco enriched with [pyridine-D4](S)-NNN for the course of this study
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55414
About this study
The purpose of this study is to better understand how people break down a tobacco specific cancer-causing toxin called N'-nitrosonornicotine (NNN) that is present in smokeless tobacco and cigarettes. Some people are able to get rid of this chemical as a harmless agent better than others. Through this research, the investigators hope to develop a better understanding of how people process potentially harmful chemicals and identify tobacco users who are in danger of developing cancer. Participants will complete questionnaires regarding their health and smoking history. The investigators will take blood samples, saliva samples, cheek cells and urine to measure exposure to toxins and harmful chemicals present in smokeless tobacco. Participants will be given smokeless tobacco study product and be asked to use only it for the entire time they are in the study. The study product contains deuterated NNN. Deuterated NNN is just like the NNN found in commercially available smokeless tobacco products, but is labeled with deuterium or heavy hydrogen atoms. Deuterium is non-toxic and safe. Using smokeless tobacco containing deuterium allows us to follow NNN as it is broken down in the body.
Read the detailed description
Fifty healthy smokeless tobacco users will be recruited by advertising in Minneapolis-St. Paul area. This research will be conducted at the Tobacco Research Center at the University of Minnesota. Regular smokeless tobacco users will be screened over the phone. If eligible after the phone screen, participants will be invited to attend an orientation visit in the clinic where consent will be obtained and subjects will fill out forms about their tobacco use and medical history. Subjects who are determined to be eligible after the orientation visit will return to the clinic for a baseline visit where they will receive the smokeless tobacco product and be instructed to use only the study product until they return for their first lab session seven days later.
Prior to each of the three lab sessions, subjects will collect all of their urine for the 24 hours leading up to their scheduled appointment. At each lab session, participants will use the study product and collect their saliva and tobacco juices at regular intervals. Participants will also swab the inside of their cheek for cells and have their blood drawn.
Collected samples will be used to characterize the metabolic activation and DNA binding of NNN.
- Conditions
- Tobacco Toxicant Exposure
- Being tested
- Deuterated NNN
- Keywords
- tobacco toxicants, smokeless tobacco, nitrosamines, tobacco specific nitrosamines (TSNAs)
- Medical subject headings
- Tobacco Use
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deuterated NNNDrug
Smokeless tobacco study product
| Study group | Role | What they receive |
|---|---|---|
| Smokeless tobacco study product | Experimental | Smokeless tobacco product spiked with deuterated NNN. Receives: Drug: Deuterated NNN |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine extent of α-hydroxylation of NNN as indicated by presence of keto acid 17 and hydroxy acid 22 in plasma
Deuterated NNN will be assessed after one week of regular use via smokeless tobacco study product, as well as during use in three lab sessions.
Measured: One week post dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2015 (estimated)
- Study start15 Apr 2018
- Primary completion21 Feb 2020
- Study completion21 Feb 2020
Why it stopped: not successful in securing the deuterated products
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (45)Papers the sponsor has linked to this study.
- Other trials for Tobacco Toxicant ExposureStudies of the same condition, open and under way.
- More trials run by 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02414477
- Sponsor's protocol ID
- 2014NTLS110
- Status last verified
- Jan 2025
- First submitted
- 23 Mar 2015
- Last updated
- 30 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Boyle, P. and Levin, P. (2008) World Cancer Report, 2008. IARC, Lyon, FR.
World Health Organization. (2012) Cancer Fact Sheet No. 297, February 2012 (http://www.who.int/mediacentre/factsheets/fs297/en/index.html).
Fontham ET, Thun MJ, Ward E, Portier KM, Balch AJ, Delancey JO, Samet JM; ACS Cancer and the Environment Subcommittee. American Cancer Society perspectives on environmental factors and cancer. CA Cancer J Clin. 2009 Nov-Dec;59(6):343-51. doi: 10.3322/caac.20041. Epub 2009 Oct 28.
PubMed 19864396Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan;63(1):11-30. doi: 10.3322/caac.21166. Epub 2013 Jan 17.
PubMed 23335087Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.
PubMed 21296855IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Personal habits and indoor combustions. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt E):1-538. No abstract available.
PubMed 23193840Centers for Disease Control and Prevention (CDC). Current cigarette smoking among adults - United States, 2011. MMWR Morb Mortal Wkly Rep. 2012 Nov 9;61(44):889-94.
PubMed 23134971Shafey, O., Eriksen, M.P., Ross, H., and Mackay, J. (2009) The Tobacco Atlas, 3rd Edition. American Cancer Society and World Lung Foundation, Atlanta, GA.
United States Department of Health and Human Services (2009) National Survey on Drug Use and Health. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Office of Applied Studies, Washington, D.C.
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Smokeless tobacco and some tobacco-specific N-nitrosamines. IARC Monogr Eval Carcinog Risks Hum. 2007;89:1-592. No abstract available.
PubMed 18335640Fiore, M.C., Jaén, C.R., and Baker, T.B. (2008) Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. U.S. Department of Health and Human Services. Public Health Service., Rockville, MD.
National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/NEJMoa1102873. Epub 2011 Jun 29.
PubMed 21714641Institute of Medicine (2012) Scientific Standards for Studies on Modified Risk Tobacco Products. National Academy Press, Washington, D.C.
Surveillance Research Program, N. C. I. (2013) Fast Stats: An interactive tool for access to SEER cancer statistics. http://seer.cancer.gov/faststats (Accessed on 5-21-2013).
American Nonsmokers' Rights Foundation. (2013) Percent of Population Covered by 100% Smokefree Restaurant AND Bar Laws. http://no-smoke.org/pdf/RBpercentMap. pdf .
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolism of Deuterated NNN in Smokeless Tobacco Users
- ClinicalTrials.gov ID
- NCT02414477
- Acronym / sponsor ID
- 2014NTLS110
- Conditions
- Tobacco Toxicant Exposure
- Keywords
- tobacco toxicants, smokeless tobacco, nitrosamines, tobacco specific nitrosamines (TSNAs)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: not successful in securing the deuterated products
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 15 Apr 2018 (actual)
- Primary completion
- 21 Feb 2020 (actual)
- Study completion
- 21 Feb 2020 (actual)
- First posted
- 10 Apr 2015 (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.
The purpose of this study is to better understand how people break down a tobacco specific cancer-causing toxin called N'-nitrosonornicotine (NNN) that is present in smokeless tobacco and cigarettes. Some people are able to get rid of this chemical as a harmless agent better than others. Through this research, the investigators hope to develop a better understanding of how people process potentially harmful chemicals and identify tobacco users who are in danger of developing cancer. Participants will complete questionnaires regarding their health and smoking history. The investigators will take blood samples, saliva samples, cheek cells and urine to measure exposure to toxins and harmful chemicals present in smokeless tobacco. Participants will be given smokeless tobacco study product and be asked to use only it for the entire time they are in the study. The study product contains deuterated NNN. Deuterated NNN is just like the NNN found in commercially available smokeless tobacco products, but is labeled with deuterium or heavy hydrogen atoms. Deuterium is non-toxic and safe. Using smokeless tobacco containing deuterium allows us to follow NNN as it is broken down in the body.
Detailed description
Fifty healthy smokeless tobacco users will be recruited by advertising in Minneapolis-St. Paul area. This research will be conducted at the Tobacco Research Center at the University of Minnesota. Regular smokeless tobacco users will be screened over the phone. If eligible after the phone screen, participants will be invited to attend an orientation visit in the clinic where consent will be obtained and subjects will fill out forms about their tobacco use and medical history. Subjects who are determined to be eligible after the orientation visit will return to the clinic for a baseline visit where they will receive the smokeless tobacco product and be instructed to use only the study product until they return for their first lab session seven days later.
Prior to each of the three lab sessions, subjects will collect all of their urine for the 24 hours leading up to their scheduled appointment. At each lab session, participants will use the study product and collect their saliva and tobacco juices at regular intervals. Participants will also swab the inside of their cheek for cells and have their blood drawn.
Collected samples will be used to characterize the metabolic activation and DNA binding of NNN.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Smokeless tobacco study product | Experimental | Drug: Deuterated NNNSmokeless tobacco product spiked with deuterated NNN. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Regular smokeless tobacco user
- Good physical health with no unstable medical conditions
- Stable and good mental health, i.e., currently do not experience unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the DSM-IV criteria, during the past six months
- Willing to perform study activities such as having blood sample drawn, saliva collection, urine collection, multiple clinic visits
- For female subjects of child bearing potential, not known to be pregnant or nursing, or planning to become pregnant within next 12 months
Key exclusion criteria (4 listed)
- Using other tobacco or nicotine containing products
- Unstable medical condition
- Currently taking any medications that affect relevant metabolic enzymes
- Not willing to use switch smokeless tobacco brand to use tobacco enriched with [pyridine-D4](S)-NNN for the course of this study
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 |
|---|---|---|
| Deuterated NNNSmokeless tobacco study product | Drug | Smokeless tobacco study product |
Primary outcome
Determine extent of α-hydroxylation of NNN as indicated by presence of keto acid 17 and hydroxy acid 22 in plasma
Time frame: One week post dosing
Deuterated NNN will be assessed after one week of regular use via smokeless tobacco study product, as well as during use in three lab sessions.
Results and safety
The study was stopped early (reason given: not successful in securing the deuterated products). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- BackgroundBoyle, P. and Levin, P. (2008) World Cancer Report, 2008. IARC, Lyon, FR.
- BackgroundWorld Health Organization. (2012) Cancer Fact Sheet No. 297, February 2012 (http://www.who.int/mediacentre/factsheets/fs297/en/index.html).
- Background: PubMed 19864396Fontham ET, Thun MJ, Ward E, Portier KM, Balch AJ, Delancey JO, Samet JM; ACS Cancer and the Environment Subcommittee. American Cancer Society perspectives on environmental factors and cancer. CA Cancer J Clin. 2009 Nov-Dec;59(6):343-51. doi: 10.3322/caac.20041. Epub 2009 Oct 28.
- Background: PubMed 23335087Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan;63(1):11-30. doi: 10.3322/caac.21166. Epub 2013 Jan 17.
- Background: PubMed 21296855Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.
- Background: PubMed 23193840IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Personal habits and indoor combustions. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt E):1-538. No abstract available.
- Background: PubMed 23134971Centers for Disease Control and Prevention (CDC). Current cigarette smoking among adults - United States, 2011. MMWR Morb Mortal Wkly Rep. 2012 Nov 9;61(44):889-94.
- BackgroundShafey, O., Eriksen, M.P., Ross, H., and Mackay, J. (2009) The Tobacco Atlas, 3rd Edition. American Cancer Society and World Lung Foundation, Atlanta, GA.
- BackgroundUnited States Department of Health and Human Services (2009) National Survey on Drug Use and Health. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Office of Applied Studies, Washington, D.C.
- Background: PubMed 18335640IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Smokeless tobacco and some tobacco-specific N-nitrosamines. IARC Monogr Eval Carcinog Risks Hum. 2007;89:1-592. No abstract available.
- BackgroundFiore, M.C., Jaén, C.R., and Baker, T.B. (2008) Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. U.S. Department of Health and Human Services. Public Health Service., Rockville, MD.
- Background: PubMed 21714641National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/NEJMoa1102873. Epub 2011 Jun 29.
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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 Phase 1 study testing Deuterated NNN in people with Tobacco Toxicant Exposure, run by 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 6 inclusion and 4 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: stopped early, as of the sponsor's last update on 30 Jan 2025. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: not successful in securing the deuterated products). Results are not available in the source record.
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?
Determine extent of α-hydroxylation of NNN as indicated by presence of keto acid 17 and hydroxy acid 22 in plasma (time frame: One week post dosing). 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 NCT02414477, which also lists 45 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 30 Jan 2025.