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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how the chemical nornicotine in smokeless tobacco transforms into a potentially harmful substance called NNN inside the body. Researchers are testing various levels of nornicotine in herbal snuff (a type of smokeless tobacco) to assess its impact on NNN formation. The goal is to determine if reducing nornicotine can lower NNN exposure, potentially leading to safer tobacco products. Individuals who have used the same smokeless tobacco brand for at least six months and exclusively use smokeless tobacco products are well-suited for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that smokeless tobacco, such as herbal snuff, carries risks. Studies have found that it contains nicotine, which can be addictive, and many chemicals that can cause cancer. People who use smokeless tobacco have a higher risk of developing heart disease, stroke, and other serious health problems.

Trials are testing herbal snuff with varying levels of nornicotine, a substance found in tobacco. While specific safety information about herbal snuff is limited, understanding the general risks of smokeless tobacco is crucial. Using it can lead to health issues at any age, and no safe amount exists.

Prospective trial participants should carefully consider these potential risks. The trial is in an early stage, so researchers are still collecting safety information. Consulting a healthcare provider is advisable to understand how it might affect health. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for smokeless tobacco use, which often involve nicotine replacement therapy or prescription medications, the herbal snuff being investigated offers a tobacco-free alternative. Researchers are excited about these treatments because they contain varying levels of herbal ingredients, such as 3.5 µg/g, 70 µg/g, and 160 µg/g, which mimic the sensory experience of commercial moist snuff without the nicotine. This could help reduce dependency on nicotine by offering a similar experience without the addictive component. Additionally, the inclusion of a control group using unmodified herbal snuff allows researchers to directly compare the effects of different active ingredient levels, potentially paving the way for a safer, non-addictive substitute for traditional smokeless tobacco products.

What evidence suggests that this trial's treatments could be effective for reducing NNN formation in smokeless tobacco users?

This trial will evaluate different formulations of herbal snuff as alternatives to traditional smokeless tobacco. Research has shown that tobacco-free herbal snuff can reduce exposure to harmful substances found in regular smokeless tobacco. For example, one study found that people significantly reduced their tobacco use when they switched to tobacco-free snuff. This finding suggests that herbal snuff might lower the risks associated with smokeless tobacco, such as certain types of cancer. However, the overall health risks of using smokeless tobacco remain a concern. Replacing traditional smokeless tobacco with a non-tobacco alternative may offer some benefits by reducing harmful exposure. ^{2 6 7 8 9}

Who Is on the Research Team?

Irina Stepanov, PhD

Principal Investigator

University of Minnesota, Division of Environmental Health Sciences

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6615745/

Smokeless tobacco reduction: Preliminary study of ... The percentage reduction in intake was 50% for the first 4 weeks and 75% for the subsequent 4 weeks. If more tobacco-free snuff was necessary to reduce ST use ...

2. harmreductionjournal.biomedcentral.com harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-021-00557-6

The health impact of smokeless tobacco products A review that pooled 11 US studies found increased odds for HNC in snuff users (OR = 1.71; 95% CI 1.08–2.70) but not for ever-tobacco chewers, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00218270

Effectiveness of Using Tobacco Free Snuff in Reducing ... This study will assess the effectiveness of using tobacco free snuff in reducing levels of exposure to tobacco and associated toxicity, as well ...

4. mayoclinic.org mayoclinic.org/diseases-conditions/nicotine-dependence/in-depth/chewing-tobacco/art-20047428

Smokeless tobacco products Because of the health risks, smokeless tobacco products aren't a good way to quit smoking. If you use chewing tobacco or other forms of smokeless tobacco, you ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7581601/

Tobacco Harm Reduction: Past History, Current ... In past and current years, Swedish snus has been demonstrated to have a lower risk for some cancers, non-fatal cardiovascular disease and pulmonary disease than ...

6. fda.gov fda.gov/tobacco-products/products-ingredients-components/dip-chew-snuff-snus-smokeless-doesnt-mean-safe

Dip, Chew, Snuff, Snus: “Smokeless” Doesn't Mean “Safe” There is no safe level of smokeless tobacco use. And smokeless users can experience health consequences at any age, even as teenagers.

7. cancer.org cancer.org/cancer/risk-prevention/tobacco/smokeless-tobacco.html

Health Risks of Smokeless Tobacco Increased risk of dying from heart disease and stroke. Increased risk of early delivery and stillbirth when used during pregnancy.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9985244/

Harmful and potentially harmful constituents (HPHCs) in ... The two ZYN products contained no nitrosamines or polycyclic aromatic hydrocarbons (PAHs) but low levels of ammonia, chromium, formaldehyde, and nickel.

9. truthinitiative.org truthinitiative.org/sites/default/files/media/files/2019/08/Smokeless-Tobacco-Fact-Sheet.pdf

smokeless tobacco Some of these Swedish snus products have been approved by the FDA as new tobacco products. This determination required the FDA to conclude that the introduction ...