Efficacy of Oral Tobacco Products Compared to a Medicinal Nicotine

Oral Tobacco as a Harm Reduction Product: Study 2 - Efficacy of Oral Tobacco Products Compared to Medicinal Nicotine for Complete Cigarette Substitution and Among Non-abstainers, for Reduction in Cigarette Smoking

For the primary goals, we hypothesize that 1) the oral tobacco product will be more efficacious than the medicinal nicotine product in substituting for smoking cigarettes; 2) among non-abstainers, the oral tobacco product will lead to greater reduction in cigarette smoking than medicinal nicotine; and 3) a higher rate of oral tobacco compared to medicinal nicotine use will be observed during and beyond the treatment period.

For the secondary goals, we hypothesize that 1) both products will equally reduce withdrawal symptoms from cigarette abstinence; and 2) the toxicant exposure and toxicity will be reduced dramatically when smokers switch from cigarettes to each of these products; however, this reduction will be greater with the use of medicinal nicotine.

Study Overview

• Status: Completed
• Conditions: Tobacco Use Disorder
• Intervention / Treatment: Drug: Nicotine Gum; Other: Oral tobacco

Detailed Description

This second study under "Oral Tobacco as a Harm Reduction Product" grant is a clinical trial. Subjects will be randomized to the brand of smokeless tobacco that is determined to be most effective in Study 1 or to nicotine gum for 12 weeks to compare complete substitution for smoking. The secondary aims are to determine the effects of the products on biomarkers of exposure and toxicity. Other secondary aim includes examining the effects of the two products on withdrawal symptoms. Two sites will be used for these studies: University of Minnesota and Oregon Research Institute (ORI).

• Study Type: Interventional
• Enrollment (Actual): 391
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota
  • Oregon
    • Eugene, Oregon, United States, 97403
      • Oregon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• smoking at least 10 cigarettes daily for the past year,
• in good physical health (no unstable medical condition;
• no contraindications for medicinal nicotine, as appropriate for the study, stable, good mental health (e.g., no recent unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the DSM-IV criteria).

Exclusion Criteria:

Subjects must not be currently using other tobacco or nicotine products; Female subjects cannot be pregnant or nursing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nicotine Gum; Nicotine replacement therapy (4 mg nicotine gum) was provided to the participants for an 12 weeks. Participants were encouraged to completely substitute nicotine gum for cigarettes and asked to use at least 6-8 pieces a day or optimally every 1-2 h and more if necessary. They were advised to reduce consumption by half during weeks 7-9 and three-quarters during weeks 10-12.	Drug: Nicotine Gum; 4 mg Nicotine gum; Other Names: Nicorette
Experimental: Snus; Oral tobacco (Camel Snus) was provided to the participants for an 12 weeks. Participants were encouraged to completely substitute snus for cigarettes and asked to use at least 6-8 pieces a day or optimally every 1-2 h and more if necessary. They were advised to reduce consumption by half during weeks 7-9 and three-quarters during weeks 10-12.	Other: Oral tobacco; Snus; Other Names: Camel Snus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Product Effect on Complete Substitution for Smoking	Number of subjects using only the assigned study product at week 6	6 week post smoking substitution
Number of Cigarettes Smoked	Cigarettes per day at mid intervention	6 weeks post cigarette substitution
Number of Products Used	Pieces of product per week at mid intervention	6 weeks post smoking substitution

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Products Effect on Withdrawal Symptoms.	Total withdrawal score on the Minnesota Nicotine Withdrawal Scale for subjects using only their assigned study product. This scale measures withdrawal symptoms from cigarettes. There are 8 items on the scale with scores that range from 0 to 4. Total score is calculated by summing the scores (excluding the craving item). Minimum score is 0 and maximum is 28. The higher the score the more severe the withdrawal.	Week 1-12 post switching
Product Effect on Biomarkers of Exposure and Toxicity	Total NNAL (e.g., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides) among those subjects who reported use of assigned product only (baseline and week 4 samples).	Baseline and Week 4 post smoking substitution

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Hatsukami DK, Severson H, Anderson A, Vogel RI, Jensen J, Broadbent B, Murphy SE, Carmella S, Hecht SS. Randomised clinical trial of snus versus medicinal nicotine among smokers interested in product switching. Tob Control. 2016 May;25(3):267-74. doi: 10.1136/tobaccocontrol-2014-052080. Epub 2015 May 19.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: July 2, 2008
• First Submitted That Met QC Criteria: July 2, 2008
• First Posted (Estimate): July 3, 2008

Study Record Updates

• Last Update Posted (Actual): December 6, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Snus; Harm Reduction; Oral Tobacco Products; Smoking Substitution; Biomarkers of Tobacco Exposure
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 1R01 CA135884-2; 1R01CA135884 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share data with both internal and external researchers. Those external researchers interested in accessing the data will be required to submit a data analyses proposal with specific aims, hypotheses, and data analyses plan. These proposals will be reviewed by the investigative team. The requested data will then be provided that includes the variable list, raw data and description of the measures and methods of data collection.