Herbal Snuff for Smokeless Tobacco Use

Overseen By Hanna Vanderloo, RN, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Metabolic enzyme-affecting drugs

Disqualifiers: Immune disorders, Respiratory diseases, Kidney, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

55 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants are not taking any medications that affect certain metabolic enzymes. If your current medications do not affect these enzymes, you may not need to stop taking them.

What data supports the effectiveness of the treatment Herbal Snuff for reducing smokeless tobacco use?

The study from northern Sweden suggests that using Swedish moist snuff (snus) may have helped reduce smoking rates, indicating that similar products might aid in reducing tobacco use. ^{1 2 3 4 5}

Is herbal snuff safe for human use?

Smokeless tobacco products, including snuff and snus, contain harmful substances that can increase the risk of oral cancer. They have toxic and cancer-causing components, making them unsafe for human health. ^{1 5 6 7 8}

How is Herbal Snuff different from other treatments for smokeless tobacco use?

Herbal Snuff is unique because it offers a non-tobacco alternative to traditional smokeless tobacco products, potentially reducing exposure to harmful tobacco constituents like nicotine and carcinogens (cancer-causing substances). Unlike other treatments that may focus on nicotine replacement or cessation aids, Herbal Snuff provides a similar user experience without the tobacco-related risks. ^{1 5 6 7 9}

What is the purpose of this trial?

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.

Research Team

Irina Stepanov, PhD

Principal Investigator

University of Minnesota, Division of Environmental Health Sciences

Eligibility Criteria

Adult smokeless tobacco users aged 18-65, using at least 3 tins per week for over 6 months, and in good physical and mental health can join. They must not be pregnant or nursing, use other nicotine products or have significant oral health issues. Participants should also not be on medications affecting metabolic enzymes.

Inclusion Criteria

I am not on medication that affects my metabolism.

I am not pregnant, nursing, or planning to become pregnant.

I am not on medication that affects my metabolism.

Exclusion Criteria

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

Your teeth and gums are in bad shape, with noticeable gum recession, cavities, or tooth loss.

I have used nicotine replacement or smoking cessation products in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive different levels of nornicotine in herbal snuff to study endogenous NNN formation

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Herbal Snuff (Smokeless Tobacco)

Trial Overview The study is examining how the body processes nornicotine from herbal snuff to form a carcinogen called NNN. It aims to understand if reducing nornicotine in these products could lower NNN exposure, potentially informing future regulations.

Participant Groups

Group I: Group 3 (N=15) Experimental Treatment 1 Intervention

3.5 µg/g herbal snuff, 5% of the lowest level found in commercial moist snuff

Group II: Group 2 (N=15) Experimental Treatment 1 Intervention

70 µg/g herbal snuff, lowest level found in commercial moist snuff (rounded)

Group III: Group 1 (N=15) Experimental Treatment 1 Intervention

160 µg/g herbal snuff, median level found in commercial moist snuff

Group IV: Group 4(N=10) Active Control 1 Intervention

0 µg/g herbal snuff, control group will use unmodified herbal snuff

Herbal Snuff (Smokeless Tobacco) is already approved in United States, European Union for the following indications:

Approved in United States as Smokeless Tobacco for:

• None approved for therapeutic use; however, it is legally available for recreational use.

Approved in European Union as Smokeless Tobacco for:

• None approved for therapeutic use; however, it is legally available for recreational use in some member states.

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Findings from Research

In a study of 10,270 secondary school students in South Africa, 12.4% reported using smokeless tobacco in the past month, with higher usage among males (13.6%) and younger students in grade 8 (15.3%).

Smokeless tobacco use was significantly associated with factors such as race, socioeconomic status, urban living, and current cigarette smoking, indicating a need for targeted interventions to address these demographics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and correlates of smokeless tobacco use among grade 8-11 school students in South Africa: a nationwide study. Reddy, PS., James, S., Resnicow, K., et al.[2022]

Most smokeless tobacco (SLT) users in Nigeria believe that SLT has various health benefits, such as clearing the eyes and nose, aiding sleep, and providing protection against colds, despite a lack of awareness about its negative health consequences.

The study highlights the need for public health initiatives to address the misconceptions surrounding SLT use, as it is a popular alternative to smoking cigarettes among indigenous African populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Between Traditions and Health: Beliefs and Perceptions of Health Effects of Smokeless Tobacco Among Selected Users in Nigeria. Adedigba, MA., Aransiola, J., Arobieke, RI., et al.[2022]

Smokeless tobacco use among adolescent and young adult males remains prevalent, posing significant health risks such as oral cancer and addiction, indicating a need for targeted interventions.

Understanding the motivations and patterns of smokeless tobacco use, including peer influence and knowledge of health risks, is crucial for developing effective prevention and cessation programs for youth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smokeless tobacco use by youth in the U.S. Boyd, GM., Glover, ED.[2023]

The study of 3,407 participants in northern Sweden from 1986 to 1999 found that the use of Swedish moist snuff (snus) was highly stable among men, with 75% of snus users maintaining their use, contributing to a decline in smoking rates.

Men who used snus were less likely to switch to cigarettes (only 2% did), and many former smokers transitioned to snus instead, indicating that snus may serve as a less harmful alternative to smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving patterns of tobacco use in northern Sweden. Rodu, B., Stegmayr, B., Nasic, S., et al.[2019]

A study analyzing 70 smokeless tobacco products from the US and Sweden found that moist and dry snuff, as well as soft pellets, contained significantly higher levels of polycyclic aromatic hydrocarbons (PAHs), with concentrations 10-60 times greater than other smokeless tobacco styles.

The research identified benzo[a]pyrene (B[a]P) as a reliable marker for PAHs in smokeless tobacco products, highlighting the need for further investigation into the sources of PAHs, especially given discrepancies in previous studies regarding naphthalene levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polycyclic aromatic hydrocarbons in US and Swedish smokeless tobacco products. McAdam, KG., Faizi, A., Kimpton, H., et al.[2021]

Chronic exposure to smokeless tobacco products, including snuff and snus, significantly reduces levels of endothelial progenitor cells and various immune cells in mice, which could impair the body's ability to repair blood vessels and increase infection risk.

Exposure to these products also leads to increased levels of the pro-inflammatory cytokine TNFα, suggesting a potential link to vascular inflammation and a higher risk of developing cardiovascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Toxicity of Smokeless Tobacco Products in Mice. Malovichko, MV., Zeller, I., Krivokhizhina, TV., et al.[2020]

A novel model mouth system was developed to simulate human buccal conditions and evaluate the release of nicotine from pouch moist snuff, showing that 60-90% of nicotine is released after 30 minutes of use.

This system can serve as an alternative tool for assessing user exposure to harmful tobacco constituents, potentially aiding in the risk evaluation of smokeless tobacco products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel model mouth system for evaluation of In Vitro release of nicotine from moist snuff. Li, P., Zhang, J., Sun, SH., et al.[2022]

Smokeless tobacco products, such as chewing tobacco and snuff, contain numerous harmful compounds, including tobacco-specific nitrosamines and heavy metals, which are linked to an increased risk of oral cancer.

The level of cancer risk associated with smokeless tobacco varies: dry snuff poses a higher risk, while moist snuff and chewing tobacco present a lower risk, indicating that the balance of carcinogenic and potentially protective compounds influences overall safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk for oral cancer from smokeless tobacco. Janbaz, KH., Qadir, MI., Basser, HT., et al.[2022]

Children living in homes with smokeless tobacco users are exposed to significantly higher levels of nicotine, with concentrations 21 times greater than in tobacco-free homes, indicating a serious risk of indirect exposure.

The study suggests that nicotine in these homes likely comes from tobacco being spilled or expectorated, highlighting the need for awareness about the risks of smokeless tobacco use around children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levels of nicotine in dust from homes of smokeless tobacco users. Whitehead, TP., Metayer, C., Park, JS., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Prevalence and correlates of smokeless tobacco use among grade 8-11 school students in South Africa: a nationwide study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Between Traditions and Health: Beliefs and Perceptions of Health Effects of Smokeless Tobacco Among Selected Users in Nigeria. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Smokeless tobacco use by youth in the U.S. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Evolving patterns of tobacco use in northern Sweden. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Polycyclic aromatic hydrocarbons in US and Swedish smokeless tobacco products. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Systemic Toxicity of Smokeless Tobacco Products in Mice. [2020]

7. England pubmed.ncbi.nlm.nih.gov

A novel model mouth system for evaluation of In Vitro release of nicotine from moist snuff. [2022]

8. Poland pubmed.ncbi.nlm.nih.gov

Risk for oral cancer from smokeless tobacco. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Levels of nicotine in dust from homes of smokeless tobacco users. [2021]