Nornicotine in Smokeless Tobacco as a Precursor for Carcinogen Exposure

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03998735
• Collaborator: (none)
• Enrollment: 55
• Location: 1
• Arms: 4
• Anticipated Duration (Months): 18.4
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

Our goal in this study is to investigate the extent of endogenous nitrosation of nornicotine in smokeless tobacco users as a function of nornicotine content in smokeless products. This study will lead to an understanding of the endogenous formation of NNN from nornicotine in humans, and will also investigate the effect of the reduction of nornicotine content in smokeless tobacco on the extent of endogenous NNN formation. The knowledge gained in this study will lead to the development of recommendations for the regulation, or potentially elimination, of nornicotine in smokeless tobacco products in order to minimize exposure to NNN in the users of these products.

Condition or Disease	Intervention/Treatment	Phase
Smokeless Tobacco	Drug: Herbal Snuff (Smokeless Tobacco)	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Nornicotine in Smokeless Tobacco as a Precursor for Carcinogen Exposure
• Actual Study Start Date: Oct 19, 2021
• Anticipated Primary Completion Date: Jan 1, 2023
• Anticipated Study Completion Date: May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 (N=15) 160 µg/g herbal snuff, median level found in commercial moist snuff	Drug: Herbal Snuff (Smokeless Tobacco); 4 levels of [D4]nornicotine in herbal snuff
Experimental: Group 2 (N=15) 70 µg/g herbal snuff, lowest level found in commercial moist snuff (rounded)	Drug: Herbal Snuff (Smokeless Tobacco); 4 levels of [D4]nornicotine in herbal snuff
Experimental: Group 3 (N=15) 3.5 µg/g herbal snuff, 5% of the lowest level found in commercial moist snuff	Drug: Herbal Snuff (Smokeless Tobacco); 4 levels of [D4]nornicotine in herbal snuff
Active Comparator: Group 4(N=10) 0 µg/g herbal snuff, control group will use unmodified herbal snuff	Drug: Herbal Snuff (Smokeless Tobacco); 4 levels of [D4]nornicotine in herbal snuff

Outcome Measures

Primary Outcome Measures

1. To investigate endogenous formation of NNN in smokeless tobacco users. [2 Weeks]

   Presence of urinary [pyridine-D4]NNN ([D4]NNN)

2. To investigate endogenous formation of NNN in smokeless tobacco users. [2 Weeks]

   Level of urinary [pyridine-D4]NNN ([D4]NNN) present

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female adult smokeless tobacco users 18-65 years of age, using at least 3 tins of product per week for 6 months;

• Used the same brand for >80% of their smokeless tobacco use over the course of at least 6 months, and used this brand exclusively for at least two weeks prior to the eligibility screening;

• Not smoking or using any other nicotine or tobacco product in the past 2 weeks (expired CO < 6 ppm);

• Participants are in good physical health (no unstable medical condition) and good general oral health as determined by the licensed medical professional;

• Participants 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 licensed medical professional;

• Participants who are not taking any medications that affect relevant metabolic enzymes;

• Women who are not pregnant or nursing or planning to become pregnant;

• Participants have provided written informed consent to participate in the study.

Exclusion Criteria:

• Significant immune system disorders, respiratory diseases, kidney or liver diseases or any other medical disorders that may affect biomarker data as determined by the licensed medical professional;

• Vital signs out of range as determined by the licensed medical professional (participants failing for vital signs will be allowed to re-screen once):

• Evident poor oral health (significant gum recession, dental caries, tooth loss) as determined by the general oral health status check;

• Excessive drinking (e.g., 5 or more drinks daily) or problems with drinking or drugs (e.g., self-report of binge drinking alcohol or treatment for drug or alcohol abuse within last 3 months); to be assessed by PI or licensed medical professional;

• Regular smoking or tobacco use (e.g., greater than once a week) other than oral smokeless tobacco products;

• Currently (within the past 2 weeks) using nicotine replacement or other tobacco cessation products (to minimize confounding effects of another product);

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Masonic Cancer Center	Minneapolis	Minnesota	United States	55411

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Irina Stepanov, PhD, University of Minnesota, Division of Environmental Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT03998735
• Other Study ID Numbers: SPH-2019-23251; 2019NTLS123; NCT02499198
• First Posted: Jun 26, 2019
• Last Update Posted: Oct 27, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Lobeline

Study Results

No Results Posted as of Oct 27, 2021