Deuterated NNN for Tobacco Exposure

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Minnesota

Must not be taking: Metabolic enzyme medications

Disqualifiers: Other tobacco, Unstable medical, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how people break down a harmful chemical called N'-nitrosonornicotine (NNN) found in smokeless tobacco. Researchers seek to determine why some individuals process this toxin more safely than others. Participants will use a special smokeless tobacco product containing a harmless, traceable version of NNN, known as Deuterated NNN, which allows researchers to track how the body handles it. The study seeks regular users of smokeless tobacco who are in good health and not using other tobacco products. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to this important scientific discovery.

Will I have to stop taking my current medications?

Yes, if you are currently taking any medications that affect certain enzymes involved in breaking down chemicals, you will need to stop taking them to participate in this study.

Is there any evidence suggesting that deuterated NNN is likely to be safe for humans?

Research has shown that deuterium, a component of deuterated NNN, is safe and non-toxic, meaning it doesn't cause harm by itself. Deuterated NNN resembles the NNN found in regular smokeless tobacco but contains heavier hydrogen atoms, allowing scientists to track its breakdown in the body.

Although specific safety data from past studies on deuterated NNN is lacking, deuterium itself is considered safe. As this treatment is in the early stages of testing, researchers are closely studying its safety in humans. Participants in this study will use a smokeless tobacco product with deuterated NNN to help researchers understand how the body processes it. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Deuterated NNN is unique because it introduces a deuterated version of NNN, a compound found in tobacco, which researchers believe could reduce the harmful effects of smokeless tobacco products. Unlike traditional cessation aids like nicotine replacement therapies or behavioral counseling, deuterated NNN specifically targets the nitrosamine compounds, potentially reducing their carcinogenic impact. Researchers are excited about this treatment as it could offer a novel approach to harm reduction for tobacco users by chemically altering the tobacco itself, rather than focusing solely on user behavior or nicotine delivery.

What evidence suggests that deuterated NNN could be effective for understanding tobacco exposure?

Research has shown that deuterated NNN helps reveal how the body breaks down N'-nitrosonornicotine (NNN), a harmful chemical in tobacco linked to cancer risk. In this trial, participants will use a smokeless tobacco product spiked with deuterated NNN to study these effects. Some individuals process NNN more effectively than others, and the study aims to understand these differences. Although no direct proof yet exists that deuterated NNN lowers cancer risk, it aids scientists in learning how the body handles NNN. This knowledge might eventually help identify tobacco users at a higher risk of cancer. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults in good physical and mental health who regularly use smokeless tobacco. They must not be pregnant, nursing, or planning pregnancy soon. Participants should not be on medications affecting metabolism enzymes, using other tobacco products, or have unstable medical conditions.

Inclusion Criteria

I am willing to give blood, saliva, and urine samples and visit the clinic multiple times.

I am in good health with no serious or unstable conditions.

You use smokeless tobacco products regularly.

Exclusion Criteria

You are not willing to switch to a specific type of tobacco that contains a certain chemical called [pyridine-D4](S)-NNN for the duration of the study.

I am on medication that affects my metabolism.

My health condition changes rapidly and unpredictably.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Phone screening and 1 in-person orientation visit

Baseline

Participants attend a baseline visit to receive the smokeless tobacco product and instructions for use

1 week

1 in-person visit

Treatment

Participants use the smokeless tobacco study product containing deuterated NNN and collect samples for analysis

1 week

3 lab sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Deuterated NNN

Trial Overview

The study tests how a toxin called N'-nitrosonornicotine (NNN) found in smokeless tobacco is broken down by users. It involves giving participants a special version of this toxin labeled with deuterium to track its breakdown in the body through blood, saliva, cheek cells, and urine samples.

How Is the Trial Designed?

Group I: Smokeless tobacco study product Experimental Treatment 1 Intervention

Smokeless tobacco product spiked with deuterated NNN.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02414477?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(lobeline))&rank=9

Metabolism of Deuterated NNN in Smokeless Tobacco Users

An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

2.

pubs.acs.org

pubs.acs.org/doi/10.1021/acs.chemrestox.1c00431

Assessment of the Exposure to NNN in the Plasma of ...

Urinary NNN is usually measured in order to assess the exposure to this toxicant for tobacco users. NNN excretion in urine can be highly biased ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9308447/

Smokeless Tobacco and Cigarette Smoking - PubMed Central

Tobacco products present a deadly combination of nicotine addiction and carcinogen exposures resulting in millions of cancer deaths per year in the world.

4.

withpower.com

withpower.com/trial/phase-1-3-2018-24cd5

Deuterated NNN for Tobacco Exposure · Info for Participants

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 ...

5.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04003

Evaluating the Metabolism of Deuterated NNN in ...

Information gathered from this study may help researchers understand how NNN is processed by the body and therefor more about the risk of smokeless tobacco use.

6.

ctv.veeva.com

ctv.veeva.com/study/metabolism-of-deuterated-nnn-in-smokeless-tobacco-users

Metabolism of Deuterated NNN in Smokeless Tobacco Users

Deuterium is non-toxic and safe. Using smokeless tobacco containing deuterium allows us to follow NNN as it is broken down in the body. Full ...

7.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK326492/

Exposure Data - Smokeless Tobacco and Some ... - NCBI - NIH

The highest TSNA levels were reported in the dark tobacco cigarettes (NNK, 370–1120 ng/cigarette; NNN, 3660–5316 ng/cigarette) (Fischer et al., 1989a,b; Tricker ...