Tobacco DependenceNCT06043362
Use of Nicotine Pouches Among Daily Smokers
A study testing 0 mg nicotine pouch, 3 mg nicotine pouch and 6 mg nicotine pouch in people with Tobacco Dependence, run by Milton S. Hershey Medical Center at 2 sites in United States.
Trial summary
The purpose of this clinical trial is to understand the health effects of a new oral nicotine pouch, and also to understand if this product can help reduce traditional cigarette smoking. The main aims are: 1. Read more about this study
- Who is it for?
- Ages 21 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Tobacco Dependence
- What is being tested?
- 0 mg nicotine pouch, 3 mg nicotine pouch and 6 mg nicotine pouch
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 375 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Sep 2024to Aug 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Commonly smoke ≥ 5 cigarettes per day (at least 2 days/week) for at least the prior 12 months
- Exhaled CO measurement of ≥ 6 parts per million at baseline
- Must be interested in reducing cigarette consumption by at least 50% and willing to try nicotine pouches
- Able to understand, read and write in English
- Access to e-mail and a smartphone/computer that has reliable internet connection
- Able to understand and give informed consent
Who cannot join
- Plans to quit smoking within the next 30 days
- Currently pregnant, breastfeeding, or planning to become pregnant in the next 6 months
- Recent (past 3 months) unstable illness that may increase risks of participation or ability to participate fully (e.g. hospitalization for a mental health condition or substance use disorder in prior 6 months, stroke or myocardial infarction in the past year)
- Serious current respiratory diseases (e.g. exacerbations of asthma or chronic obstructive pulmonary disease [COPD], requiring oxygen or oral prednisone), kidney disease (e.g. requiring dialysis), liver disease (e.g cirrhosis), or any medical disorder/medication that may affect participant safety or biomarker data
- Use of a nicotine pouch or other non-cigarette nicotine product (e-cigarette, pipe, cigar, chew, snus, hookah, IQOS) for 5 or more days in the past 28 days
- Use of illegal drugs daily or weekly in the past 3 months
Show all 9Show fewer
- Use of combustible (smoked) recreational or medical marijuana weekly in the past 3 months (less frequent smoked medical marijuana or use of other forms of medical marijuana are ok)
- Other member of the household currently participating in the study
- Any other condition that in the opinion of the investigator would make it unlikely that the participant could comply with the study protocol
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Penn State College of Medicine
Hershey, Pennsylvania, 17033
Nicolle M Krebs, MS, 717-531-5673, nkrebs@pennstatehealth.psu.edu
Jonathan Foulds, PhD
- Recruiting
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Jason Robinson, PhD, 713-745-3581, jdrobinson@mdanderson.org
About this study
Official title: Randomized Placebo-controlled Trial of Nicotine Pouches in Smokers
The purpose of this clinical trial is to understand the health effects of a new oral nicotine pouch, and also to understand if this product can help reduce traditional cigarette smoking. The main aims are:
- Understand the impact of nicotine pouch use on toxicant exposure biomarkers, and indicators of potential harms to health.
- Examine the influence of nicotine pouch use on conventional tobacco product use (cigarettes).
Participants will be randomized to one of six nicotine pouch groups (3 nicotine strengths, each with 2 potential flavors) to use over 16 weeks and asked to reduce their cigarette smoking over that time by at least 75% by substituting with the use of the nicotine pouches. Researchers will compare the outcomes of the different nicotine pouch strengths and flavors to each other. Participants will be asked to complete study questionnaires and provide urine, exhaled carbon monoxide, and mouth cell samples, and other health measurements.
Read the detailed description
Nicotine Pouches represent a rapidly growing category in the U.S. tobacco market, but little is known about their health effects (including addiction) or effects on cigarette smoking. The investigators propose to use a randomized controlled trial methodology to inform FDA on the effects of nicotine pouch use in smokers interested in reducing their smoking but not quitting smoking. The specific aim of this proposal is to recruit a cohort of 330 current daily smokers with an interest in reducing smoking, and to measure a comprehensive battery of behavioral and health indicators at baseline, and over 16 weeks after being randomized to use Nicotine Pouches containing either 0mg, 3mg or 6mg nicotine in "Smooth" or Wintergreen flavors in a randomized double-blind, placebo-controlled trial. The trial will be conducted at two sites: Penn State Hershey and M.D. Anderson in Texas in order to recruit a diverse sample of smokers. This trial therefore addresses the scientific domain of Product Composition and Design (specifically nicotine content and flavor additives). The central hypothesis is that key markers of toxicity and health effects (e.g. urine NNAL, exhaled carbon monoxide [CO], measures of cigarette addiction [e.g. Penn State Cigarette Dependence Index], oxidative stress and oral B(a)P DNA adducts) will be significantly reduced in smokers who are provided high nicotine (6mg) Nicotine Pouches, relative to 0mg pouches. The investigators will also assess the effects of Nicotine Pouch content on Nicotine Pouch addiction, and the effects of pouch nicotine dose on cigarette and other tobacco product consumption. Lastly, investigators will also compare the effects in those randomized to "Smooth" versus Wintergreen flavors. After the 16-week randomized phase, participants will be encouraged to quit smoking and connected to telephone cessation services and then followed-up 4 weeks later (week 20) in order to ascertain whether the nicotine content of the pouches influenced intention and ability to quit smoking. At the completion of this rigorous double-blind randomized trial investigators will have a better understanding of the effects of Nicotine Pouches (and their nicotine content and flavor characteristics) on cigarette consumption and the resulting changes to markers of health risks, oral health and nicotine addiction.
- Conditions
- Tobacco Dependence
- Being tested
- 0 mg nicotine pouch, 3 mg nicotine pouch, 6 mg nicotine pouch, Smooth nicotine pouch, Wintergreen nicotine pouch
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
0 mg nicotine pouchOther
Oral nicotine pouches that contain 0 mg of nicotine
3 mg nicotine pouchOther
Oral nicotine pouches that contain 3 mg of nicotine
6 mg nicotine pouchOther
Oral nicotine pouches that contain 6 mg of nicotine
Smooth nicotine pouchOther
Non-flavored nicotine pouches that are characterized as smooth.
Wintergreen nicotine pouchOther
Menthol flavored nicotine pouches that are characterized as wintergreen.
| Study group | Role | What they receive |
|---|---|---|
| 0 mg + Smooth flavor | Experimental | Participants are provided with zero strength (0 mg) nicotine pouches with smooth flavor. Receives: Other: 0 mg nicotine pouch; Other: Smooth nicotine pouch |
| 3 mg + Smooth flavor | Experimental | Participants are provided with medium strength (3 mg) nicotine pouches with smooth flavor. Receives: Other: 3 mg nicotine pouch; Other: Smooth nicotine pouch |
| 6 mg + Smooth flavor | Experimental | Participants are provided with high strength (6 mg) nicotine pouches with smooth flavor. Receives: Other: 6 mg nicotine pouch; Other: Smooth nicotine pouch |
| 0 mg + Wintergreen flavor | Experimental | Participants are provided with zero strength (0 mg) nicotine pouches with wintergreen flavor. Receives: Other: 0 mg nicotine pouch; Other: Wintergreen nicotine pouch |
| 3 mg + Wintergreen flavor | Experimental | Participants are provided with medium strength (3 mg) nicotine pouches with wintergreen flavor. Receives: Other: 3 mg nicotine pouch; Other: Wintergreen nicotine pouch |
| 6 mg + Wintergreen flavor | Experimental | Participants are provided with high strength (6 mg) nicotine pouches with wintergreen flavor. Receives: Other: 6 mg nicotine pouch; Other: Wintergreen nicotine pouch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of urinary NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol)
Measure of tobacco-specific nitrosamine
Measured: Week 16
Secondary outcomes (7)
Level of carbon monoxide in exhaled breath
Measure of cigarette smoke exposure obtained with an exhaled carbon monoxide monitor
Measured: Week 16
Concentration of urinary cotinine
Measure of nicotine exposure
Measured: Week 16
Penn State Cigarette Dependence Index score
Measure of cigarette dependence via the Penn State Cigarette Dependence Index. Scale range is 0-20. Higher scores indicate more dependence.
Measured: Week 16
Penn State Nicotine Pouch Dependence Index score
Measure of nicotine pouch dependence via the Penn State Nicotine Pouch Dependence Index. Scale range is 0-20. Higher scores indicate more dependence.
Measured: Week 16
Mean number of cigarettes per day
Measure of mean cigarettes smoked per day
Measured: Week 16
Number of cigarette-free days
Measure of number of days abstinent from cigarettes (self-reported)
Measured: Randomization (Week 0) - Week 16
7-day point prevalence cigarette abstinence
Measure of 7-day point prevalence abstinence biochemically validated with exhaled carbon monoxide < 7ppm
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start17 Sep 2024
- Primary completionJan 2028 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tobacco DependenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 375 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Jonathan Foulds, Milton S. Hershey Medical Center
- Investigators
- Jonathan Foulds, PhD, Principal investigator, Penn State College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06043362
- Sponsor's protocol ID
- STUDY00023056
- Other IDs
- 1U54DA058271
- Status last verified
- Oct 2026
- First submitted
- 12 Sep 2023
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Researchers not involved in the execution of this proposed study may request de-identified individual participant data (IPD) collected in the study by contacting the principal investigator, Dr. Jonathan Foulds.
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Placebo-controlled Trial of Nicotine Pouches in Smokers
- ClinicalTrials.gov ID
- NCT06043362
- Acronym / sponsor ID
- STUDY00023056
- Conditions
- Tobacco Dependence
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 375 participants (estimated)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 17 Sep 2024 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 21 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this clinical trial is to understand the health effects of a new oral nicotine pouch, and also to understand if this product can help reduce traditional cigarette smoking. The main aims are:
- Understand the impact of nicotine pouch use on toxicant exposure biomarkers, and indicators of potential harms to health.
- Examine the influence of nicotine pouch use on conventional tobacco product use (cigarettes).
Participants will be randomized to one of six nicotine pouch groups (3 nicotine strengths, each with 2 potential flavors) to use over 16 weeks and asked to reduce their cigarette smoking over that time by at least 75% by substituting with the use of the nicotine pouches. Researchers will compare the outcomes of the different nicotine pouch strengths and flavors to each other. Participants will be asked to complete study questionnaires and provide urine, exhaled carbon monoxide, and mouth cell samples, and other health measurements.
Detailed description
Nicotine Pouches represent a rapidly growing category in the U.S. tobacco market, but little is known about their health effects (including addiction) or effects on cigarette smoking. The investigators propose to use a randomized controlled trial methodology to inform FDA on the effects of nicotine pouch use in smokers interested in reducing their smoking but not quitting smoking. The specific aim of this proposal is to recruit a cohort of 330 current daily smokers with an interest in reducing smoking, and to measure a comprehensive battery of behavioral and health indicators at baseline, and over 16 weeks after being randomized to use Nicotine Pouches containing either 0mg, 3mg or 6mg nicotine in "Smooth" or Wintergreen flavors in a randomized double-blind, placebo-controlled trial. The trial will be conducted at two sites: Penn State Hershey and M.D. Anderson in Texas in order to recruit a diverse sample of smokers. This trial therefore addresses the scientific domain of Product Composition and Design (specifically nicotine content and flavor additives). The central hypothesis is that key markers of toxicity and health effects (e.g. urine NNAL, exhaled carbon monoxide [CO], measures of cigarette addiction [e.g. Penn State Cigarette Dependence Index], oxidative stress and oral B(a)P DNA adducts) will be significantly reduced in smokers who are provided high nicotine (6mg) Nicotine Pouches, relative to 0mg pouches. The investigators will also assess the effects of Nicotine Pouch content on Nicotine Pouch addiction, and the effects of pouch nicotine dose on cigarette and other tobacco product consumption. Lastly, investigators will also compare the effects in those randomized to "Smooth" versus Wintergreen flavors. After the 16-week randomized phase, participants will be encouraged to quit smoking and connected to telephone cessation services and then followed-up 4 weeks later (week 20) in order to ascertain whether the nicotine content of the pouches influenced intention and ability to quit smoking. At the completion of this rigorous double-blind randomized trial investigators will have a better understanding of the effects of Nicotine Pouches (and their nicotine content and flavor characteristics) on cigarette consumption and the resulting changes to markers of health risks, oral health and nicotine addiction.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 0 mg + Smooth flavor | Experimental | Other: 0 mg nicotine pouch, Other: Smooth nicotine pouchParticipants are provided with zero strength (0 mg) nicotine pouches with smooth flavor. |
| 3 mg + Smooth flavor | Experimental | Other: 3 mg nicotine pouch, Other: Smooth nicotine pouchParticipants are provided with medium strength (3 mg) nicotine pouches with smooth flavor. |
| 6 mg + Smooth flavor | Experimental | Other: 6 mg nicotine pouch, Other: Smooth nicotine pouchParticipants are provided with high strength (6 mg) nicotine pouches with smooth flavor. |
| 0 mg + Wintergreen flavor | Experimental | Other: 0 mg nicotine pouch, Other: Wintergreen nicotine pouchParticipants are provided with zero strength (0 mg) nicotine pouches with wintergreen flavor. |
| 3 mg + Wintergreen flavor | Experimental | Other: 3 mg nicotine pouch, Other: Wintergreen nicotine pouchParticipants are provided with medium strength (3 mg) nicotine pouches with wintergreen flavor. |
| 6 mg + Wintergreen flavor | Experimental | Other: 6 mg nicotine pouch, Other: Wintergreen nicotine pouchParticipants are provided with high strength (6 mg) nicotine pouches with wintergreen flavor. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Commonly smoke ≥ 5 cigarettes per day (at least 2 days/week) for at least the prior 12 months
- Exhaled CO measurement of ≥ 6 parts per million at baseline
- Must be interested in reducing cigarette consumption by at least 50% and willing to try nicotine pouches
- Able to understand, read and write in English
- Access to e-mail and a smartphone/computer that has reliable internet connection
Key exclusion criteria (9 listed)
- Plans to quit smoking within the next 30 days
- Currently pregnant, breastfeeding, or planning to become pregnant in the next 6 months
- Recent (past 3 months) unstable illness that may increase risks of participation or ability to participate fully (e.g. hospitalization for a mental health condition or substance use disorder in prior 6 months, stroke or myocardial infarction in the past year)
- Serious current respiratory diseases (e.g. exacerbations of asthma or chronic obstructive pulmonary disease [COPD], requiring oxygen or oral prednisone), kidney disease (e.g. requiring dialysis), liver disease (e.g cirrhosis), or any medical disorder/medication that may affect participant safety or biomarker data
- Use of a nicotine pouch or other non-cigarette nicotine product (e-cigarette, pipe, cigar, chew, snus, hookah, IQOS) for 5 or more days in the past 28 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 0 mg nicotine pouchOral nicotine pouches that contain 0 mg of nicotine | Other | 0 mg + Smooth flavor, 0 mg + Wintergreen flavor |
| 3 mg nicotine pouchOral nicotine pouches that contain 3 mg of nicotine | Other | 3 mg + Smooth flavor, 3 mg + Wintergreen flavor |
| 6 mg nicotine pouchOral nicotine pouches that contain 6 mg of nicotine | Other | 6 mg + Smooth flavor, 6 mg + Wintergreen flavor |
| Smooth nicotine pouchNon-flavored nicotine pouches that are characterized as smooth. | Other | 0 mg + Smooth flavor, 3 mg + Smooth flavor, 6 mg + Smooth flavor |
| Wintergreen nicotine pouchMenthol flavored nicotine pouches that are characterized as wintergreen. | Other | 0 mg + Wintergreen flavor, 3 mg + Wintergreen flavor, 6 mg + Wintergreen flavor |
Primary outcome
Concentration of urinary NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol)
Time frame: Week 16
Measure of tobacco-specific nitrosamine
7 secondary outcomes
Level of carbon monoxide in exhaled breath
Time frame: Week 16
Concentration of urinary cotinine
Time frame: Week 16
Penn State Cigarette Dependence Index score
Time frame: Week 16
Penn State Nicotine Pouch Dependence Index score
Time frame: Week 16
Mean number of cigarettes per day
Time frame: Week 16
Number of cigarette-free days
Time frame: Randomization (Week 0) - Week 16
7-day point prevalence cigarette abstinence
Time frame: Week 16
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Individual participant dataSharing planned: Yes. Researchers not involved in the execution of this proposed study may request de-identified individual participant data (IPD) collected in the study by contacting the principal investigator, Dr. Jonathan Foulds.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jonathan Foulds, PhD principal investigator
Penn State College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 0 mg nicotine pouch, 3 mg nicotine pouch and 6 mg nicotine pouch in people with Tobacco Dependence, run by Milton S. Hershey Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicolle M Krebs, MS (717-531-5673, nkrebs@pennstatehealth.psu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of urinary NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (time frame: Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.