Metabolism of Deuterated NNN in Smokeless Tobacco Users

January 28, 2025 updated by: University of Minnesota
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55414
        • University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Smokeless tobacco study product
Smokeless tobacco product spiked with deuterated NNN.
Drug: Deuterated NNN
Smokeless tobacco study product

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
One week post dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 15, 2018

Primary Completion (Actual)

February 21, 2020

Study Completion (Actual)

February 21, 2020

Study Registration Dates

First Submitted

March 23, 2015

First Submitted That Met QC Criteria

April 7, 2015

First Posted (Estimated)

April 10, 2015

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 28, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 2014NTLS110

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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