Pexacerfont to Reduce Stress-induced Tobacco Craving

Summary

Participation Requirements

Description

Objective: To evaluate pexacerfont, an orally available, brain-penetrant selective CRF1 antagonist, for its ability to modulate emotional and motivational processes in daily smokers who are seeking to quit smoking. Study population: We will collect evaluable data from up to 60 adult, greater than or...

Objective: To evaluate pexacerfont, an orally available, brain-penetrant selective CRF1 antagonist, for its ability to modulate emotional and motivational processes in daily smokers who are seeking to quit smoking. Study population: We will collect evaluable data from up to 60 adult, greater than or equal to 10 cigarettes per day smokers who smoke their first cigarette within one hour of waking as reported on the Fagerstrom Test of Nicotine Dependence (FTND) and wish to quit smoking. Design: Participants will be randomly assigned to one of two groups to receive 30 days of oral pexacerfont (300 mg/day loading dose for 7 days, followed by 100 mg/day maintenance dose for 23 days) or matching placebo under double-blind conditions. On Day 15 and 16, subjects will have two days of testing to evaluate reactivity to stressful/neutral stimuli with and without the presence of smoking cues. Reactivity will be tested in terms of physiological parameters, subjective reports, nicotine reinforcemen, smoking resistance paradigms and functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) signal at rest and in response to stress/cue-related tasks. In addition, during the last 14 days of study drug administration, subjects will attempt to stop smoking. Daily assessments of smoking behavior will be obtained. Finally, on days 26 and 27, participants will again have two days of testing to evaluate reactivity to stressful/neutral stimuli. Reactivity will be tested in terms of physiological parameters, subjective reports, cue reactivity paradigms and functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) signal at rest and in response to stress/cue-related tasks. Outcome measures: Outcome measures in laboratory sessions will include nicotine reinforcement, latency to lapse in a smoking resistance paradigm, subjective ratings of stress, mood, and tobacco craving, autonomic responses (galvanic skin response, heart rate, and blood pressure), endocrine responses (salivary cortisol and salivary (alpha) amylase, a measure of endogenous adrenergic activity during stress), and fMRI BOLD signal at rest and in response to stress/cue-related tasks. Outcome measures during the quit attempt will include, change in consumption, number of lapses, and latency to lapse.

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