Current smoking cessation treatments are ineffective for the majority of smokers. Thus there is an urgent need to develop more effective treatment strategies. This project will comprise two large-scale randomized controlled clinical trials designed to evaluate the efficacy of an enhanced adaptive treatment strategy for smoking cessation. The essence of our unique approach to adaptive treatment is to begin treatment with state-of-the-art nicotine replacement therapy (NRT), which is initiated 2 weeks before a target quit-smoking date. We will subsequently adapt the treatment approach based on smokers'initial response to NRT and other baseline variables assessed prior to the target quit date. Our overarching hypothesis is that we will enhance cessation outcomes by adapting phannacologic treatments based on individual subject characteristics and ad lib smoking during the time when smokers are receiving pre-cessation NRT. Study 1, to be conducted in years 1-3, will evaluate a specific two-phase adaptive treatment algorithm. We will initiate pre-cessation nicotine patch treatment 2 weeks before a target quit-smoking date. If, after one week's exposure to NRT, participants do not show a favorable therapeutic response (assessed by the early outcome marker of reduced ad lib smoking before the quit date), they will be randomized to receive "rescue treatments with bupropion SR (Zyban), varenicline (Chantix), or will remain on NRT (control). Study 2, to be conducted in years 4-5, will evaluate an additional candidate medication, using the same adaptive treatment strategy as in Study 1. The selection of the candidate treatment will be based on available preclinical and clinical evidence from the other center projects as well as findings from other laboratories, using criteria described in the Research Plan. Candidate medications will include the neurosteroids DHEA and pregnenolone, other GABAergic, glutamatergic, or monoaminergic agents as well as nicotinic subtype selective ligands. Clinical trial decisions and results will be enhanced by information on individual subject characteristics, including quit success genotypes, dependence level, gender, as well as psychiatric and substance use comorbidities. Combined information from these baseline characteristics and smoking during pre-cessation NRT are likely to provide powerful predictors of which medication and treatment regimens are most likely to succeed for different smokers. The knowledge gained from these studies will provide an important new therapeutic approach to guide health care providers in delivering the most effective cessation treatments that are best adapted to the needs of each smoker.

Public Health Relevance

Cigarette smoking is the leading preventable cause of disease and death in the U.S. This health burden can be reduced substantially by quitting smoking, and yet current smoking cessation treatments have limited effectiveness. By conducting clinical trials to develop and evaluate promising adaptive treatment approaches to smoking cessation, this project has the potential to have a major positive impact on public health.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA027840-04
Application #
8499281
Study Section
Special Emphasis Panel (ZDA1-EXL-T)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$225,567
Indirect Cost
$81,896
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Briggs, Scott A; Hall, Brandon J; Wells, Corinne et al. (2016) Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats. Pharmacol Biochem Behav 142:1-7
Levin, Edward D; Hall, Brandon J; Chattopadhyay, Autri et al. (2016) Reduction of nicotine self-administration by chronic nicotine infusion with H1 histamine blockade in female rats. Psychopharmacology (Berl) 233:3009-15
Hall, Brandon J; Slade, Susan; Wells, Corinne et al. (2015) Bupropion-varenicline interactions and nicotine self-administration behavior in rats. Pharmacol Biochem Behav 130:84-9
Larrauri, José A; Burke, Dennis A; Hall, Brandon J et al. (2015) Role of nicotinic receptors in the lateral habenula in the attenuation of amphetamine-induced prepulse inhibition deficits of the acoustic startle response in rats. Psychopharmacology (Berl) 232:3009-17
Brody, Arthur L; McClernon, Francis Joseph (2015) Prediction of smoking cessation with treatment: the emerging contribution of brain imaging research. Neuropsychopharmacology 40:1309-10
Potenza, Marc N (2015) Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. Defining and classifying non-substance or behavioral addictions. J Behav Addict 4:139-41
Walton, Kevin M; Abrams, David B; Bailey, William C et al. (2015) NIH electronic cigarette workshop: developing a research agenda. Nicotine Tob Res 17:259-69
Levin, Edward D; Wells, Corinne; Johnson, Joshua E et al. (2015) Amitifadine, a triple monoamine re-uptake inhibitor, reduces nicotine self-administration in female rats. Eur J Pharmacol 764:30-7
Hall, Brandon J; Slade, Susan; Allenby, Cheyenne et al. (2015) Neuro-anatomic mapping of dopamine D1 receptor involvement in nicotine self-administration in rats. Neuropharmacology 99:689-95
Rezvani, Amir H; Cauley, Marty C; Levin, Edward D (2014) Lorcaserin, a selective 5-HT(2C) receptor agonist, decreases alcohol intake in female alcohol preferring rats. Pharmacol Biochem Behav 125:8-14

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