Highdose Nicotine Patch Therapy for Smokeless Tobacco Use

Smokeless tobacco use ("chewing") is associated with negative health effects. To date, no medications have been shown to help chewers quit long-term. High dose nicotine patch therapy may improve the chances that chewers can quit for good. If found to be effective, chewers may use this treatment to help them quit and reduce their risk for negative health effects.

Study Overview

• Status: Completed
• Conditions: Smokeless Tobacco Use
• Intervention / Treatment: Drug: nicotine replacement therapy (nicotine patches); Drug: placebo NRT

Detailed Description

Approximately 8.2 million (3.3%) of Americans ≥ 12 years of age are current smokeless tobacco (ST) users, and the prevalence of ST use has increased over the past three years. ST is increasingly being promoted as a harm reduction strategy for cigarette smoking, and two of the world's largest cigarette manufacturers have entered the ST market. ST use is estimated to be the greatest exogenous source of human exposure to cancer-causing nitrosamines. ST has been associated with oral and extra-oral cancer as well as cardiovascular and cerebrovascular mortality.

A need for efficacious interventions exists as 64% of ST users report the desire to quit. However, no pharmacotherapy has proven efficacy for increasing long-term (> 6 months) tobacco abstinence rates among ST users compared to placebo. New pharmacotherapies, drug combinations, and improved dosing of existing pharmacotherapies are needed. Previous research with nicotine patches for ST users using standard doses (up to 21 mg/day) have not increased long-term abstinence rates. However, studies of higher dose nicotine patch therapy (up to 63 mg/day) in ST users have demonstrated a dose-dependent reduction in tobacco withdrawal symptoms as well as preliminary evidence of increased long-term (> 6 months) abstinence rates compared to lower doses. The purpose of this study is to evaluate the efficacy of high dose nicotine patch therapy (42 mg/day) for increasing the 7-day point prevalence and prolonged all tobacco and ST abstinence rates at end-of-treatment (week 8), 12 and 24 weeks compared to placebo in ST users who use ≥ 3 cans/pouches per week when all subjects receive behavioral treatment for tobacco dependence. To accomplish our aims, we will randomize 60 ST users in a clinical pilot study. The work will be conducted at the Mayo Clinic in Rochester, MN.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. are at least 18 years of age and at most 55 years of age;
2. report daily ST use for the past 12 months;
3. identify ST as their primary tobacco product;
4. use an average of ≥ 3 cans/pouches per week;
5. are in general good health (determined by medical history and screening physical examination);
6. have been provided with, understand, and have signed the informed consent.

Exclusion Criteria:

1. are currently using (past 30 days) any other behavioral or pharmacologic tobacco treatment program;
2. are currently pregnant or lactating;
3. have had unstable angina, myocardial infarction, or coronary angioplasty within the past 3 months;
4. have a history of arrhythmia or an abnormal tracing on the baseline EKG;
5. have a blood pressure of greater than 140/90 or a pulse of more than 110 beats per minute;
6. have a history of severe skin allergies or dermatoses;
7. have a history of intolerance to nicotine patches;
8. have another member of their household already participating in this study;
9. are taking a medication known to interact with nicotine (i.e., clozapine);
10. are taking any prescription medication for depression or asthma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active; 2 nicotine patches each at 21 mg/day for a total of 42 mg/day for 8 weeks	Drug: nicotine replacement therapy (nicotine patches); 2- 21 mg patches per day for 8 weeks
Placebo Comparator: placebo; 2 patches (containing non active ingredients) per day for 8 weeks	Drug: placebo NRT; 2 placebo patches (containing no active ingredient)per day for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
End of Treatment (Week 8) Point Prevalence Abstinence	7 day point prevalence abstinence at the end of treatment, biochemically confirmed by urinary anabasine < 2 ng per ml	weeks 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Point-prevalence Abstinence at 3 Months	7 day point prevalence abstinence from tobacco at 3 months, biochemically confirmed using urinary anabasine < 2 ng per ml	week 12
Point-prevalence Abstinence at 6 Months	7 day point prevalence abstinence from all tobacco at 6 months, biochemically confirmed using urinary anabasine < 2 ng per ml.	week 24

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Study Chair: Jon O Ebbert, MD, Mayo Clinic

Publications and helpful links

General Publications

• Ebbert JO, Croghan IT, Schroeder DR, Hurt RD. A randomized phase II clinical trial of high-dose nicotine patch therapy for smokeless tobacco users. Nicotine Tob Res. 2013 Dec;15(12):2037-44. doi: 10.1093/ntr/ntt097. Epub 2013 Jul 19.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: July 10, 2009
• First Submitted That Met QC Criteria: July 13, 2009
• First Posted (Estimate): July 14, 2009

Study Record Updates

• Last Update Posted (Estimate): May 19, 2014
• Last Update Submitted That Met QC Criteria: May 8, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: smokeless tobacco; tobacco dependence; tobacco cessation; tobacco use; nicotine replacement; chewing tobacco; snuff; tobacco abstinence
• Additional Relevant MeSH Terms: 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: 09-002581; CA140125; 09-001763