An Effectiveness Trial of Maintenance Therapy for Nicotine Dependence

The transdermal nicotine patch is the most widely used form of tobacco dependence treatment in the US and Europe, but most smokers are unable to successfully quit with this form of treatment. Failure to respond to this treatment may, to a large extent, be due to the use of nicotine patches for only 8 weeks, the recommended treatment duration. We have found in a controlled randomized clinical trial that using the nicotine patch for 24 weeks can increase quit rates significantly. We propose here a clinical trial to replicate and extend these results to a community setting in the real-world, using the same research design utilized in clinical trials to demonstrate the effectiveness of methadone maintenance therapy for opiate dependence. Specifically, 540 smokers will receive counseling and standard (8-weeks), extended (24-weeks), or maintenance (52 weeks) therapy with transdermal nicotine patches. The main outcome is biochemically-verified smoking cessation at week 52. The cost-effectiveness, safety, and mechanism of effect (e.g., promotion of recovery following a lapse) for maintenance therapy with transdermal nicotine will also be assessed. The study results may change how we treat nicotine dependence with transdermal nicotine.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: Transdermal nicotine patch

Detailed Description

The transdermal nicotine patch is the most widely used form of tobacco dependence treatment in the US and Europe. Yet, abstinence rates following patch treatment are only ~20% at 6-months and ~9% at 12-months. There is a growing recognition that nicotine dependence is a chronic disease, like asthma or diabetes, which requires maintenance therapy. While current guidelines established by the USDHHS's Public Health Service (PHS) recommend 8-week duration for transdermal nicotine therapy, support for this recommendation is limited. In a recent randomized placebo-controlled efficacy trial comparing standard (8-week) vs. extended (24-weeks) treatment with nicotine patches, we found that, at 24 weeks, point-prevalence abstinence rates were 30% in the 24-week arm vs. 20% in the standard therapy arm (p < .05); however, by week 52, 6 months after treatment was discontinued for the extended treatment arm, the quit rates were equivalent across the treatment arms. This was the first clinical trial to suggest that the benefits of extended treatment with transdermal nicotine are largely dependent on the continuation of active treatment. However, as an efficacy trial, this study was conducted under highly-controlled conditions with strict inclusion/exclusion criteria to enhance internal validity. If recommendations for the duration of nicotine patch therapy are to be formally revised to encourage maintenance therapy, these findings must be replicated and extended under "real-world circumstances" in an effectiveness trial. In addition, as done in clinical trials to support the use of methadone maintenance for opiate dependence, a replication study must include a treatment arm that receives maintenance therapy throughout the duration of the trial (52 weeks). Thus, we propose to conduct a randomized effectiveness trial to evaluate the benefits of maintenance therapy with transdermal nicotine patches for smoking cessation. Specifically, 540 smokers will receive brief counseling and will be randomized to: standard (8-weeks), extended (24-weeks), or maintenance (52 weeks) transdermal nicotine therapy. The primary outcome will be biochemically verified 7-day point prevalence abstinence at week 52. Additional study aims include assessing: 1) treatment side effects across study arms; 2) longitudinal patterns of relapse and recovery across treatment arms; 3) mediators and moderators of treatment effects; and 4) cost-effectiveness. Overall, the trial findings will provide critical data for future PHS reviews of maintenance therapy with transdermal nicotine for subsequent treatment guidelines; for third-party payer assessments of maintenance transdermal nicotine as a covered benefit; and for individual smokers' decisions to use maintenance transdermal nicotine through over-the-counter access. In turn, this study may help to attain the Healthy People 2010 goals of reducing the US rate of tobacco use.

• Study Type: Interventional
• Enrollment (Actual): 525
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Participants will be: 1) males and females over age 18 who smoke at least 10 cigarettes/day; 2) able to communicate in English; 3) able to use NRT safely (e.g., no allergy to latex, no serious abnormal ECG reading); 4) able to provide written informed consent for study procedures; and 5) residing in the geographic area for at least 12 months.

Exclusion Criteria: Participants will be ineligible for the trial if they: 1) are unable to communicate in English; 2) Have a current diagnosis of psychosis and/or manic depression; 3) have a current medical condition that would make using transdermal nicotine patch unsafe (e.g., allergy to latex, serious, abnormal ECG reading)- participants with asthma, diabetes, hypertension, or heart disease (e.g., coronary artery disease, abnormal heart rhythm, an arrhythmia) will be permitted to enroll in the study with medical clearance from the participant's physician or the study physician; 4) have had a heart attack within the past 6 months, 5) are pregnant or planning to become pregnant or lactating, or 6) are currently enrolled or plan to enroll in another research or smoking cessation program within the next 12 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 8 weeks transdermal nicotine; 8 weeks of transdermal nicotine	Drug: Transdermal nicotine patch; Transdermal nicotine, 21mg/day
Active Comparator: 24 weeks transdermal nicotine; 24 weeks of transdermal nicotine	Drug: Transdermal nicotine patch; Transdermal nicotine, 21mg/day
Experimental: 52 weeks transdermal nicotine; 52 weeks of transdermal nicotine	Drug: Transdermal nicotine patch; Transdermal nicotine, 21mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Point Prevalence Abstinence	self-reported abstinence from smoking for 7 days prior to the assessment and biochemically confirmed with breath carbon monoxide	52-week
Week 24 Point Prevalence Abstinence	self-reported abstinence from smoking for 7 days prior to the assessment and biochemically confirmed with breath carbon monoxide	24-week

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Brian Hitsman, PhD, Northwestern University

Publications and helpful links

General Publications

• Schnoll RA, Goelz PM, Veluz-Wilkins A, Blazekovic S, Powers L, Leone FT, Gariti P, Wileyto EP, Hitsman B. Long-term nicotine replacement therapy: a randomized clinical trial. JAMA Intern Med. 2015 Apr;175(4):504-11. doi: 10.1001/jamainternmed.2014.8313.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: January 11, 2010
• First Submitted That Met QC Criteria: January 11, 2010
• First Posted (Estimate): January 13, 2010

Study Record Updates

• Last Update Posted (Estimate): July 8, 2015
• Last Update Submitted That Met QC Criteria: June 10, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: nicotine replacement therapy, smoking cessation, transdermal nicotine
• 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: DESPR DA025078; R01DA025078-02 (U.S. NIH Grant/Contract)