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Use of Nicotine Pouches Among Daily Smokers

Not Applicable
Not yet recruiting
Conditions
Tobacco Dependence
Interventions
Other: 0 mg nicotine pouch
Other: 3 mg nicotine pouch
Other: 6 mg nicotine pouch
Other: Smooth nicotine pouch
Other: Wintergreen nicotine pouch
Registration Number
NCT06043362
Lead Sponsor
Milton S. Hershey Medical Center
Brief 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. Understand the impact of nicotine pouch use on toxicant exposure biomarkers, and indicators of potential harms to health.

2. 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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
375
Inclusion Criteria
  • 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
Exclusion Criteria
  • 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
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
0 mg + Smooth flavor0 mg nicotine pouchParticipants are provided with zero strength (0 mg) nicotine pouches with smooth flavor.
0 mg + Smooth flavorSmooth nicotine pouchParticipants are provided with zero strength (0 mg) nicotine pouches with smooth flavor.
3 mg + Smooth flavor3 mg nicotine pouchParticipants are provided with medium strength (3 mg) nicotine pouches with smooth flavor.
0 mg + Wintergreen flavor0 mg nicotine pouchParticipants are provided with zero strength (0 mg) nicotine pouches with wintergreen flavor.
3 mg + Smooth flavorSmooth nicotine pouchParticipants are provided with medium strength (3 mg) nicotine pouches with smooth flavor.
6 mg + Smooth flavorSmooth nicotine pouchParticipants are provided with high strength (6 mg) nicotine pouches with smooth flavor.
0 mg + Wintergreen flavorWintergreen nicotine pouchParticipants are provided with zero strength (0 mg) nicotine pouches with wintergreen flavor.
6 mg + Wintergreen flavorWintergreen nicotine pouchParticipants are provided with high strength (6 mg) nicotine pouches with wintergreen flavor.
6 mg + Smooth flavor6 mg nicotine pouchParticipants are provided with high strength (6 mg) nicotine pouches with smooth flavor.
3 mg + Wintergreen flavor3 mg nicotine pouchParticipants are provided with medium strength (3 mg) nicotine pouches with wintergreen flavor.
3 mg + Wintergreen flavorWintergreen nicotine pouchParticipants are provided with medium strength (3 mg) nicotine pouches with wintergreen flavor.
6 mg + Wintergreen flavor6 mg nicotine pouchParticipants are provided with high strength (6 mg) nicotine pouches with wintergreen flavor.
Primary Outcome Measures
NameTimeMethod
Concentration of urinary NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol)Week 16

Measure of tobacco-specific nitrosamine

Secondary Outcome Measures
NameTimeMethod
Level of carbon monoxide in exhaled breathWeek 16

Measure of cigarette smoke exposure obtained with an exhaled carbon monoxide monitor

Mean number of cigarettes per dayWeek 16

Measure of mean cigarettes smoked per day

7-day point prevalence cigarette abstinenceWeek 16

Measure of 7-day point prevalence abstinence biochemically validated with exhaled carbon monoxide \< 7ppm

Concentration of urinary cotinineWeek 16

Measure of nicotine exposure

Penn State Cigarette Dependence Index scoreWeek 16

Measure of cigarette dependence via the Penn State Cigarette Dependence Index. Scale range is 0-20. Higher scores indicate more dependence.

Penn State Nicotine Pouch Dependence Index scoreWeek 16

Measure of nicotine pouch dependence via the Penn State Nicotine Pouch Dependence Index. Scale range is 0-20. Higher scores indicate more dependence.

Number of cigarette-free daysRandomization (Week 0) - Week 16

Measure of number of days abstinent from cigarettes (self-reported)

Trial Locations

Locations (2)

Penn State College of Medicine

🇺🇸

Hershey, Pennsylvania, United States

University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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