Engaging Working Memory and Distress Tolerance to Aid Smoking Cessation
Phase: NA
Conditions: Smoking Cessation
Sponsor: Boston University Charles River Campus

 
 
Engaging Working Memory and Distress Tolerance to Aid Smoking Cessation 
NCT03565497 
R21 DA046963 
 
Updated: 8/5/2019 
 

PROTOCOL 
Design Overview 
This study is designed to evaluate the success of mechanistic target engagement in two specific contexts:  
under standard smoking conditions and under nicotine deprivation (stress) conditions. After screening, 
consent, and baseline assessment, participants selected on the basis of inclusion/exclusion criteria will be 
randomized to one of three intervention conditions: (1) a health-education control condition (CC), (2) a 
mindfulness training condition (MT), or (3) a mindfulness training condition combined with training applying 
mindfulness skills in the context of interoceptive exposure (Mindfulness+IE). Following 6 sessions of these 
interventions, delivered over 3 weeks, participants will then undergo the standard smoking assessment of 
mechanistic targets. Two days later (and matching the progression to quit-attempt challenges following 
treatment), participants will undergo the deprivation window assessment (14 hours of smoking abstinence) of 
these same mechanistic targets, followed by evaluation of lapse behavior and smoking topography in the 
McKee paradigm to yield: (1) latency to initiate smoking during a monetarily reinforced delay period, (2) the 
number of cigarettes smoked during a subsequent 60-minute self-administration period, and (3) exploratory 
analysis of smoking topography: puff volume, puff duration, and inter-puff interval. Participants will be recruited 
to Boston University through study advertisements targeted to low SES neighborhoods, with attention to health 
service centers and religious institutions serving low SES individuals. Investigators will work closely together to 
ensure the scientific integrity (rigor and reproducibility) of the project and data analyses. 
Participant Selection 
 
We anticipate consenting and randomizing up to 107 participants in order to reach an assessed sample 
(defined as providing post-treatment assessments, including the McKee  protocol) of 75, low SES, male and 
female smokers (ages 18-65). For inclusion in the study, participants must (1) be between 18 and 65 years of 
age; (2) have reported household income of less than $30,000 per year; (3) be a regular smoker for at least 
one year; (4) report daily smoking (minimum of 5 cigarettes per day and biochemically confirmed via Carbon 
Monoxide [CO] analysis; > .10ppm CO); and (5) and not be presently engaged in a quit attempt. Exclusion 
criteria include history of psychosis as determined by a brief psychotic screen, pregnancy, nursing mothers, 
medical conditions that would contraindicate smoking (e.g., current diagnoses of chronic medical diseases 
including heart disease, chronic obstructive pulmonary disease, or seizure disorders - assessed during 
telephone prescreen and initial assessment via medical checklist), nicotine use other than cigarette smoking, 
current use of any pharmacotherapy for smoking cessation, or insufficient command of the English language 
(i.e., cannot carry on a conversation with an interviewer in the English language or read associated text).   
Feasibility and Participant Compensation 
The study team and consultants have a rich publication history reflecting collaboration on studies of health 
behaviors, distress intolerance, and, specifically smoking characteristics and treatment outcome.1,73,76,90-93  Dr. 
Otto at Boston University has a history of successfully attracting smokers for psychopathology studies, easily 
completing 100 screens per year. Moreover, Dr. Otto is directing mindfulness interventions to low SES 
adolescents recruited to his ongoing study, R21DA041531.   Recruitment/adherence is aided in the current 
study by financial compensation for all assessments and intervention sessions, with compensation of up to 
$180 per participant, depending on McKee Lapse paradigm results.   
Procedures and the McKee Protocol 
Following telephone screening for basic eligibility, participants will be scheduled for an informed consent 
interview and subsequent baseline assessment session. Interventions are to be completed over the 
subsequent 3 weeks, and post-treatment assessments of the mechanistic targets are scheduled for one-week 
(standard smoking assessment) and one week + 2 days (deprivation-window assessment) from the last 
intervention session. For the standard smoking window assessments, participants are asked to smoke .5 hour 
before the scheduled assessment session. The deprivation-window assessment is scheduled two days later, 
(for example, scheduled for 12:00 noon, with smoking to cease at 10PM the night before). Upon arrival to the 
lab, nicotine abstinence will be verified by expired CO levels, as determined by a cut-off of half of the 
participant’s screening session CO concentration or <10 PPM (those failing will be rescheduled). After 
verification of abstinence, participants will complete assessment of the triple-risk mechanistic target variables. 
These assessments will be followed by the McKee Lapse protocol (Dr. McKee, Study Consultant, will train the 
study team and help monitor quality in these procedures): participants will be instructed that over the next 50 
min, they will have the option to initiate a cigarette self-administration (smoking) session at any point or to 
delay initiation in exchange for monetary reinforcement. If participants choose to delay, they will be awarded 
funds for each 5-minute increment they are able to resist smoking. Once participants choose to end the delay 
period in order to smoke (or resist smoking for the entire 50 minute delay period), they will then participate in a 
60-minute cigarette self-administration session, in which they will be given the choice to either smoke their 

preferred brand of cigarettes or receive monetary reinforcement for cigarettes not smoked. Participants will be 
given funds at the beginning of the self-administration session and will lose a portion of the funds for each 
cigarette smoked. When participants smoke in this protocol, we will use the Clinical Research Support System 
(CReSS; Plowshare Technologies, Borgwaldt KC, Inc) to measure smoking topography. The reliability and 
acceptability of use of the portable CReSS device is well documented,88,94 and is recommended over direct 
observation. Topography data will include puff CO volume, puff duration, and inter-puff interval. Puff level data 
will be averaged to compute mean topography variables for each participant.  
Baseline Assessments 
• Demographics. Participants will be asked to provide standard demographic information (age, gender, 
race/ethnicity) as well as history of medical problems and current treatments.  
• Smoking History Questionnaire. Smoking history and pattern will be assessed with a semi-structured 
interview with items targeting smoking frequency, age of smoking initiation, years of being a regular 
smoker, etc. The Timeline follow-back method will be used to establish degree of cigarette use in the last 
30 days (a baseline predictor). 
• Fagerström Test for Cigarette Dependence (FTCD). The FTCD is a six-item scale designed to assess 
gradations in cigarette dependence.95 The FTCD will be used as a baseline covariate in the analyses.  
• Questionnaire of Smoking Urges-Brief (QSU-Brief). The QSU-Brief measures urge to smoke and 
craving.96,97 The baseline and deprivation window Total Craving Scores will be used as predictors. 
• Executive Function – Behavioral Regulation.  Baseline levels of behavioral regulation will be assessed 
with the Behavioral Regulation Index from the from the SOBC assay, Behavioral Rating Inventory of 
Executive Function – Adults (BRIEF-A, http://scienceofbehaviorchange.org/measures/). 
• Psychological Distress.  Baseline levels of psychological distress will be assessed with the SOBC assay, 
Kessler Psychological Distress Scale (K6+, http://scienceofbehaviorchange.org/measures/).  
Mechanistic Targets: The Triple-Risk Variables 
Each of the mechanistic targets will be assessed at the post-intervention standard-smoking and deprivation-
window assessments.   
• Negative Affectivity/Stress:  Negative affect will be assessed with the SOBC assay, PANAS (PANAS-
state negative  (http://scienceofbehaviorchange.org/measures/), and withdrawal symptoms will be 
assessed with the Wisconsin Smoking Withdrawal Scale (WSWS).98 Each of these mechanistic targets will 
be assessed at the standard smoking and deprivation-window assessments.   
• WM. We focus on WM capacity as a mechanistic target due to its centrality to executive functions; its 
predictive validity across a wide range of health behavior applications, specifically including smoking; 
relevance as a modifiable treatment target; and interaction with negative affectivity/stress.1 To provide 
multi-domain assessment of  WM,99,100 we will adopt 3 specific SOBC assays : Adaptive N-Back, Digit 
Span, and Spatial Span (http://scienceofbehaviorchange.org/measures/).  Dr. Bickel, Study Consultant, will 
aid the study team in quality control for these assessments. 
• Distress Tolerance. We likewise focus on DT as a mechanistic target due to its predictive validity across a 
wide range of health behaviors (specifically including smoking); relevance as a modifiable treatment target; 
and amplification of negative affectivity/stress.1 Because self-report and behavioral measures of DT are 
only partially correlated,35 we will utilize both assessment strategies. For self-report we will use the ASI-3, 
an 18-item measure of AS.101 The ASI-3 has sound psychometric properties, including excellent internal 
consistency, predictive validity, and reliability among treatment-seeking smokers.102 Behavioral Distress 
Tolerance will be assessed with the computerized Mirror-Tracing Persistence Task (MTPT-C),103  with 
evidence this measure captures the inability to tolerate distress and not just the experience of distress 
itself.104 Dr. Zvolensky and Smits will aid the study team in quality control for these assessments. 
Interventions  
All interventions are delivered in six, 90-minute individual sessions over 3 weeks. Sessions will be recorded for 
supervision/quality assurance review by Dr. Otto. 
• CC: The wellness education control condition (CC) will be modeled after that used in our studies of 
exercise for smoking cessation,73 but delivered in an individual format. Content focuses on discussions of a 
variety of healthy lifestyle topics, such as healthy eating, time management, recommended health 
screenings, and cancer and cardiovascular prevention. Content is delivered using a combination of 
lectures, videos, handouts, and discussions while allowing participants to set their own realistic wellness 
goals, which they can gradually incorporate into their lives. Dr. Smits, Study Consultant, will aid the study 
team in quality control of this intervention. 

• MT: Mindfulness training will be adapted for 6 individual sessions from previous MT manuals for substance 
dependence.105-107 The length of treatment in the current protocol corresponds well to the mean number of 
sessions [5.2] attended by smokers in treatment, even when eight sessions are offered.105 Formal 
intervention elements include: (1) a body scan designed to teach participants to pay attention to specific 
parts of their bodies as a strategy to increase attentional capacities/reduce habitual mind-wandering;  (2) 
non-judgmental awareness, and (3) ‘awareness of breath’ meditation, with an additional focus on helping 
participants become more aware of the present moment and refrain from habitually engaging in self-related 
pre-occupations concerning the future or the past. Informal daily practices include (1) performing daily 
activities mindfully, (2) setting daily aspirations, and (3) techniques designed for cravings (recognize/ 
accept/investigate mind-states, emotions, and body sensations from moment-to-moment). Participants will 
be asked to record both the number of minutes and number of episodes of mindfulness practice each day 
using structured diaries. Dr. Witkiewitz, Study Consultant, will aid the study team in adapting mindfulness 
skill training to the current protocol, and consult with Dr. Otto on treatment fidelity issues.   
• MT+IE.  This condition will mirror the MT condition for the first 4 individual sessions, then for the final 2 
individual sessions, MT will be rehearsed under conditions of sensations of anxiety/tension induced by 
interoceptive exposure procedures (IE). Dr. Otto and the study team are adept in delivering IE training to 
those about to undergo benzodiazepine withdrawal sensations,69-71 and to smokers as part of quit 
attempts.74,75  In the two in-session rehearsals (sessions 5 & 6 of mindfulness training), the focus will be on 
maintaining mindful, non-judgmental awareness despite the presence of induced bodily sensations of 
anxiety/tension.