Cigarette smoking, the leading cause of preventable death in the United States, almost universally begins in adolescence. Smokers in this especially vulnerable age group are often interested in quitting, but are rarely successful when making quit attempts on their own. In light of this, and given the considerable health benefit of quitting smoking at a young age, evidence-based treatments for adolescent smoking cessation are critically needed. Surprisingly little research has addressed this need, and almost all of it has focused on psychosocial approaches, yielding generally small treatment effect sizes. Pharmacotherapy, while well established as a cessation treatment in adult smokers, has been the focus of only 6 controlled trials in adolescent smokers. These trials of nicotine replacement therapy and bupropion SR have produced mixed but generally encouraging results. Varenicline, a 42 nicotinic acetylcholine receptor partial agonist, has demonstrated superior cessation efficacy in adults across several randomized trials when compared to placebo, nicotine replacement therapy, and bupropion SR. Given its striking efficacy as an adult smoking cessation treatment, varenicline is a strong candidate for evaluation in adolescent smokers. Guided by dosing recommendations from an adolescent pharmacokinetic study and feasibility/safety information from an adolescent pilot cessation trial, a randomized, double blind placebo-controlled trial of varenicline for adolescent smoking cessation is proposed. Participants will be randomized to receive varenicline or placebo for 12 weeks, with multiple post-treatment follow-up visits through 6 months. Weekly psychiatric &medical visits, including detailed, rigorous safety/tolerability assessment, will be conducted throughout active treatment. All participants will concurrently participate in a contingency management intervention, designed to enhance study retention. The primary efficacy hypothesis is that participants receiving varenicline, compared with those receiving placebo, will demonstrate greater biologically confirmed 7-day point prevalence abstinence at the end of treatment. We further hypothesize adequate safety and tolerability, compared with placebo, in the frequency of treatment-emergent adverse events. The proposed study will fill a critical evidence gap, and has the potential to significantly advance adolescent smoking cessation treatment. Whether findings are positive, null, or negative, this will be an important contribution to the literature and will have considerale clinical and public health impact.

Public Health Relevance

Cigarette smoking in adolescence is a serious problem with significant health consequences. Adolescent smokers have a hard time quitting cigarettes, and we need to develop effective treatments to help them. Varenicline, the most effective medication to help adults quit smoking, has not been tested in adolescents. Thus, the proposed study will investigate varenicline to help adolescents quit smoking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DA031779-03
Application #
8660680
Study Section
Risk, Prevention and Intervention for Addictions Study Section (RPIA)
Program Officer
Biswas, Jamie
Project Start
2012-06-01
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$670,803
Indirect Cost
$208,582
Name
Medical University of South Carolina
Department
Psychiatry
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
McClure, Erin A; Baker, Nathaniel L; Gipson, Cassandra D et al. (2015) An open-label pilot trial of N-acetylcysteine and varenicline in adult cigarette smokers. Am J Drug Alcohol Abuse 41:52-6
McClure, Erin A; Gipson, Cassandra D; Malcolm, Robert J et al. (2014) Potential role of N-acetylcysteine in the management of substance use disorders. CNS Drugs 28:95-106
McClure, Erin A; Baker, Nathaniel L; Gray, Kevin M (2014) Cigarette smoking during an N-acetylcysteine-assisted cannabis cessation trial in adolescents. Am J Drug Alcohol Abuse 40:285-91
McClure, Erin A; Sonne, Susan C; Winhusen, Theresa et al. (2014) Achieving cannabis cessation -- evaluating N-acetylcysteine treatment (ACCENT): design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network. Contemp Clin Trials 39:211-23
McClure, Erin A; Acquavita, Shauna P; Dunn, Kelly E et al. (2014) Characterizing smoking, cessation services, and quit interest across outpatient substance abuse treatment modalities. J Subst Abuse Treat 46:194-201
McClure, Erin A; Saladin, Michael E; Baker, Nathaniel L et al. (2013) Smoking topography and abstinence in adult female smokers. Addict Behav 38:2833-6
Lewis, A Lee; Baker, Nathaniel; Carpenter, Matthew et al. (2013) Does physician continuity within a clinical trial increase retention and compliance among adolescent smokers? Adolesc Psychiatry (Hilversum) 3: