Pexacerfont to Reduce Stress-induced Tobacco Craving

Nicotine Dependence Clinical Trial

Official title: Pexacerfont for Reduction of Stress-induced Tobacco Craving, Nicotine Reinforcement, and Brain Activation in Humans

Status Withdrawn

Clinical Trial Summary

Background:

• Stressful situations often cause tobacco cravings. These cravings can make it very difficult for smokers who are trying to quit. Research has shown that craving may involve hormone pathways in the brain. The anti-anxiety drug pexacerfont acts on these hormone pathways. Researchers want to see if pexacerfont can act on the brain and lessen stress-related tobacco cravings in smokers who are trying to quit.

Objectives:

• To test the effects of pexacerfont on tobacco craving in smokers who want to quit smoking.

Eligibility:

• Smokers between 18 to 55 years of age who are trying to quit. (Participants must have smoked at least 10 cigarettes per day for at least 1 year.)

Design:

• Participants will be screened with a physical exam and medical history.

• Participants will be assigned to take either pexacerfont or a placebo. They will take three pills every morning for the first 7 days, then one pill every morning for 23 days.

• At the first visit, participants will provide blood and urine samples. They will then be asked to prepare a 5-minute speech and give it to the study researchers. They will also be asked to do mental math problems for another 5 minutes. During these tests, blood pressure, heart rate, sweating, and skin temperature will be measured. Participants will fill out questionnaires about stress levels, tobacco cravings, and personal experiences.

• Participants will take the study pills for 30 days. Before the 2-week point, participants will be asked to try to quit smoking for 2 weeks.

• Participants will have four study visits. These visits will involve brain imaging scans and emotional stress tests. Tobacco cravings and other stress levels will be measured at each study. Blood and urine samples may be collected at these studies.

• Participants will have follow-up visits and phone calls for up to 6 months after the end of the study visits.

Clinical Trial 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 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. ;

Related Conditions & MeSH terms

• Nicotine Dependence
• Tobacco Use Disorder

• NCT number: NCT01557556
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Status: Withdrawn
• Start date: February 24, 2012
• Completion date: December 16, 2013