Clinical trial NCT03670212: Investigation of Nicotine Seeking Behavior in Current Smokers
Official title: Neuropharmacological Investigation of Frontostriatal Network Function and Nicotine Seeking Behavior in Current Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cigarette Smoking
Keywords: cigarette smoking
acute stress
executive function
craving
nicotine seeking
relapse
excitatory neural activity
glutamate
negative affect
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2018-09-13
Enrollment: 21
Sex: ALL
Minimum age (years): 21
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Double-blind, placebo-controlled, and randomized cross-over study design. Each subject completed both the placebo and acute stress experimental sessions.
Primary purpose: BASIC_SCIENCE

Brief summary: In this study, 21 non-treatment-seeking cigarette smokers were recruited to investigate the effects of acute stress on brain function and nicotine seeking/self-administration behavior.

Detailed description: Non-treatment-seeking cigarette smoking individuals were recruited from the Detroit, MI area. Individuals were screened for cardiovascular, neurological, and psychiatric contraindications. 21 healthy smokers completed two oral pre-treatment experimental sessions (on separate non-consecutive days) in randomized order under double-blind conditions: placebo (lactose) and stress (54mg yohimbine and 10mg hydrocortisone). Yohimbine + hydrocortisone elicit a neurochemical and physiological response that mimics a 'natural' stressor. Placebo and stress sessions were identical and started at 11am. Upon arrival, subject sobriety was confirmed with expired breath alcohol measurement (\<.02%). At 11:30am, each subject smoked 6 cigarette puffs (preferred brand; provided by study) over 5 minutes to control for recent nicotine exposure. Throughout each experimental session, subjects periodically completed self-reported measures of cigarette craving, nicotine withdrawal symptoms, affect, and anxiety, and vital signs were measured. Subjects self-administered (swallowed) oral doses of yohimbine (or placebo) at 11:45am and hydrocortisone (or placebo) at 12:15pm. At 1pm, subjects completed a 60-min neuroimaging scan which included: 1) T1-weighted structural scan, 2) proton functional magnetic resonance spectroscopy (fMRS) acquisition from the left prefrontal cortex during a letter 2-back working memory paradigm, and 3) functional magnetic resonance imaging (fMRI) acquisition during an N-back paradigm yoked with cigarette cues. At 2:30pm, subjects completed an 11-trial choice progressive ratio task in which they could earn cigarette puffs (preferred brand; provided by study) or money. At 3pm, subjects self-administered earned cigarette puffs (video monitored). Subjects remained on site until 4pm discharge.

Eligibility criteria: Inclusion Criteria:

* 1) Aged between 21-35 years old, 2) current smokers (expired breath carbon monoxide \> 4ppm, self-reported 10+ cigarettes/day, Fagerstrom test for nicotine dependence score \> 3, 3) normal seated and resting vital signs (systolic blood pressure 80-160mmHg, diastolic blood pressure 50-90mmHg, and heart rate 50-90 bpm), and 4) normal or corrected-normal vision.

Exclusion Criteria:

* 1) Abnormal electrocardiogram (reviewed by licensed cardiologist), 2) magnetic resonance imaging contraindications (e.g. metal implants), 3) medical/neurological contraindications (e.g., diabetes or head trauma), 4) pregnancy (urine test; females only), 5) positive urine test result for opioids, cocaine metabolites, benzodiazepines, barbiturates, or amphetamines, 6) psychiatric contraindications (subject met criteria for current Axis 1 disorder \[other than nicotine dependence\] as indicated by computerized MINI-6 screen), and 7) self-reported marijuana and/or alcohol use on 15+ days in the past month.

Primary outcomes:
measure: Cigarette puff vs. money choice task
timeFrame: 30 minutes
Secondary outcomes:
measure: Letter 2-back task
timeFrame: 12 minutes
measure: Cigarette-cued letter N-back task
timeFrame: 15 minutes
Other outcomes:
measure: Minnesota Nicotine Withdrawal Scale
timeFrame: 1 minute; collected five times throughout each experimental session
measure: Brief Questionnaire of Smoking Urges
timeFrame: 1 minute; collected five times throughout each experimental session
measure: State-Trait Anxiety Inventory
timeFrame: 1 minute; collected five times throughout each experimental session
measure: Positive-Negative Affect Scale
timeFrame: 1 minute; collected five times throughout each experimental session
measure: Blood pressure
timeFrame: 1 minute; collected six times throughout each experimental session
measure: Heart Rate
timeFrame: 1 minute; collected six times throughout each experimental session
Locations:
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
Study officials:
affiliation: Wayne State University
name: Eric A Woodcock, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cox LS, Tiffany ST, Christen AG. Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings. Nicotine Tob Res. 2001 Feb;3(1):7-16. doi: 10.1080/14622200020032051.
citation: Spielberger CD. Assessment of state and trait anxiety: Conceptual and methodological issues. Southern Psychologist 2(4): 6-16, 1985.
citation: Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. doi: 10.1037//0022-3514.54.6.1063.
citation: Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986 Mar;43(3):289-94. doi: 10.1001/archpsyc.1986.01800030107013.