Improving Functional Outcomes of Veterans With PTSD and Tobacco Dependence
Phase: PHASE1
Conditions: Tobacco, Posttraumatic Stress Disorder
Sponsor: VA Office of Research and Development

 
 
 
 
 
 
NCT02576899 
Improving Functional Outcomes of Veterans with PTSD and Tobacco Dependence 
Study Protocol with Statistical Analysis Plan 
 
April 23, 2018 

Improving Functional Outcomes of Veterans with PTSD and Tobacco Dependence 
Study Protocol with Statistical Analysis Plan 
 
 
The present study will involve a randomized clinical trial of 50 Veterans with tobacco dependence and 
PTSD randomized to ACT-PT vs. the American Lung Association’s Freedom From Smoking program [FFS]). 
This study has two primary aims:   
AIM 1: Evaluate the relative feasibility and acceptability of ACT-PT vs. FFS.  
AIM 2: Evaluate the preliminary efficacy of ACT-PT vs. FFS with the primary outcomes of tobacco use, 
PTSD symptoms, health-related quality of life, and functional impairment.  
 
Treatment Procedures. 50 Veterans with PTSD and tobacco dependence will be randomized to ACT-PT 
(n=25) or FFS (n=25).  
 
ACT Treatment Components. The following eight components are emphasized in ACT-PT: 1) Identifying 
Problems with Control: Participants identify efforts to control or avoid smoking-related internal experiences and 
how this is problematic for quitting smoking. 2) Acceptance: Participants face smoking urges and PTSD-related 
experiences with mindful acceptance rather than avoid them. 3) Mindfulness: Participants engage in 
mindfulness exercises in order to practice nonjudgmental acceptance of internal smoking and PTSD-related 
experiences. 4) Valued living: Participants clarify their values and goals (i.e., quitting smoking, work 
achievement, social connections), and identify barriers that prevent them from achieving life goals. 5) Triggers: 
Internal (e.g., thoughts, feelings, bodily sensations) vs. external smoking triggers are identified, and Veterans 
practice acceptance and mindfulness to manage these experiences. 6) Exposure: Participants create exposure 
hierarchies for PTSD-related triggers and other internal experiences related to smoking, face them with mindful 
acceptance, and become more comfortable with these experiences. 7) Cognitive Defusion: Participants learn 
that they are not their anxieties or fears, and they mindfully observe and accept these internal experiences. 8) 
Behavioral Activation: Participants identify life goals and increase activities to replace smoking as a behavior 
used to manage anxiety, stress, and to fill idle time. Participants commit to achieving valued goals. 
 
ACT-PT procedures. Participants will receive nine 50-minute weekly individual counseling sessions, with a 
booster session one month following the final session. Session 1 is devoted to an explanation of the treatment 
rationale. Sessions 2-4 focus on acceptance, mindfulness, cognitive defusion, behavioral activation, and skills 
practice, with an emphasis on tolerance of PTSD-related triggers and replacing smoking with positive life 
activities. Session 5 is the scheduled quit week when the nicotine patch is started. Sessions 6-9 focus on 
acceptance and mindfulness of nicotine withdrawal, cravings, and PTSD symptoms, as well as behavioral 
activation. Sessions 1-6 will occur weekly; sessions 7-9 will take place every other week. A booster session will 
take place one month after the end of the main course of treatment. 
 
Control Condition. The American Lung Association’s Freedom from Smoking program (FFS) [49-51], 
commonly used in community treatment programs, will be the control condition.  FFS will consist of the same 
dosage / intensity of psychosocial treatment or nine 50-minute individual counseling sessions, with a booster 
session one month following the final session. The first session will discuss the health effects of smoking. The 
second session will discuss coping strategies for smoking urges. Sessions 3-4 will focus on the benefits of 
quitting. The scheduled quit date for participants is Session 5 (when the nicotine patch is started) and will focus 
on managing nicotine withdrawal symptoms. Sessions 6-9 will focus on relapse prevention and non-smoking 
lifestyle choices (e.g., weight management, exercise). Sessions 1-6 will occur weekly, sessions 7-9 will take 
place every other week. A booster session will take place one month after the main course of treatment. FFS 
does not include mindfulness practices, places a greater focus on psychoeducation and less emphasis on 
affect regulation as an obstacle to quitting compared to ACT.    
 
Rationale for FFS. After reviewing the literature, and carefully weighing pros and cons of many options 
[52-57], FFS was chosen as the comparison condition for several reasons: 1) FFS and similar treatments are 
usual care in many VA smoking cessation clinics [58]; 2) FFS is an effective treatment [49, 59]; and 3) this 
control condition has been previously used in other mindfulness smoking cessation studies [60]. We 
considered many alternatives, including historical controls, a no-treatment group, a minimal treatment 
condition, waitlist controls, or a nonspecific (“placebo”) therapy [54, 55, 61]. A 16-week waitlist is likely to lead 
to significant attrition, and it would be problematic to ask Veterans to wait over 4 months for treatment. We 
decided it best to focus on evaluating ACT-PT compared to one of the most common tobacco treatments.  
  
 
Therapists and therapist training procedures. Four psychology postdoctoral fellows will be trained and 
treat Veterans (two in Year 1 and two in Year 2). We will use a systematic procedure for teaching therapists to 
deliver ACT-PT and FFS in a competent and reliable fashion. Training components include: 1) reviewing the 

manual; 2) listening to portions of selected treatment tapes that illustrate methods; 3) role playing techniques; 
4) participating in a structured workshop to enhance familiarity with the theory of the treatment; and 5) ongoing 
supervision. After the didactic training in both ACT-PT and FFS, therapists will participate in three mock 
therapy sessions and the PI will provide them with feedback. The therapists’ first two cases will be closely 
monitored through weekly supervision and reviews of session videotapes.  
 
Inclusion/Exclusion Criteria  Inclusion Criteria: 1) Current DSM-5 PTSD, 2) Minimum score of 38 (clinical 
cutoff for PTSD) on the PTSD Checklist for DSM-5, 3) A regular smoker for at least 3 years, 4) Currently 
smoking at least 10 cigarettes per day, 5) Able to communicate meaningfully with the investigator, 6) 
Competent to provide written informed consent, 7) Ages 18 and older. Exclusion Criteria: 1) Current unstable 
DSM-5 bipolar disorder (i.e., instability characterized by two or more manic or depressive episodes in the past 
12 months, and a current Young Mania Rating Scale total score ≥ 13 or a current BDI score ≥ 19), 2) Any 
lifetime DSM-5 psychotic disorder, 3) Current or recent (within 1 month of study entry) moderate or severe 
DSM-5 alcohol or drug use disorder, 4) Use of other tobacco products, 5) Current use of any smoking 
cessation medications (including bupropion), 6) a cognitive impairment that would interfere with participation, 
7) A suicide attempt or severe suicidal ideation within the past 3 months, 8) Presence of any clinical features 
requiring inpatient or partial hospital treatment, 9) Pregnant or lactating women, or women of childbearing age 
that are not using a medically acceptable form of contraception, 10) Severe generalized skin disorder, 11) 
Nicotine patch allergy, 12) Recent myocardial infarction within the past 3 months, and 13) Unstable angina.  
 
Recruitment. Participants will be 50 Veterans recruited from the PI’s Tobacco Cessation Program at the 
Bedford VAMC. Based on the rate of PTSD and characteristics of Veterans in our clinic, 320 Veterans would 
meet eligibility criteria for the study during the two-year study period. Of note, if needed, 2800 other Veterans in 
the Bedford system would meet study criteria. Therefore, we do not anticipate difficulty recruiting the proposed 
number of participants. If recruitment fails to proceed at the expected rate in the first 3 months, we will modify 
recruitment procedures and/or add more recruitment sites (e.g., Primary Care, Mental Health Clinic).  
 
 
Screening Procedures. Callers will be screened by phone. Eligible participants will be scheduled for an in-
person assessment with the PI, who will confirm study eligibility and obtain informed consent. After consent, 
participants will complete clinician-rated assessments and self-report measures (see below). As in our stage 
1a trial, a psychiatrist will assess participants to determine whether they are medically cleared for the study. 
 
Assessment Measures. A broad range of reliable and valid measures will be used (see Table 2).  
 
Table 2. Outcome Measures for the RCT 
Measure 
Rater 
Self 
 
Baseline 
Weekly 
Monthly 
End of 
Tx 
1-month  
Follow-
Up 
3-Month  
Follow-
Up 
Tobacco Use  
 
 
 
 
 
 
 
 
      Number of Cigarettes 
 
X 
X 
X 
 
X 
X 
X 
      CO Level 
X 
 
X 
X 
 
X 
X 
X 
      QSU 
 
X 
X 
X 
 
X 
X 
X 
      Contemplation Ladder 
 
X 
X 
X 
 
X 
X 
 
Quality of Life 
 
 
 
 
 
 
 
 
     SF-36 
 
X 
X 
 
X 
X 
X 
X 
     Q-LES-Q 
 
X 
X 
 
X 
X 
X 
X 
     SCQoL 
 
X 
X 
X 
 
X 
X 
X 
     SDS 
 
X 
X 
 
X 
X 
X 
X 
     WSAS 
 
X 
X 
 
X 
X 
X 
X 
Psychiatric 
 
 
 
 
 
 
 
 
     PCL 
 
X 
X 
X 
 
X 
X 
X 
     BDI-II 
 
X 
X 
X 
 
X 
X 
X 
Process 
 
 
 
 
 
 
 
 
     AAQ 
 
X 
X 
 
X 
X 
X 
X 
     MAAS 
 
X 
X 
 
X 
X 
X 
X 
     VLQ 
 
X 
X 
 
X 
X 
X 
X 
Satisfaction 
 
 
 
 
 
 
 
 
     CSQ-8 
 
X 
 
 
 
X 
 
 
 
 
Diagnostic Measures: The Structured Clinical Interview for DSM-V (SCID-5-RV) is a reliable semi-
structured instrument that is the gold standard for diagnosing mental health disorders [63, 64]. The Young 
Mania Rating Scale is a reliable and validated measure that will be used to screen for bipolar disorder [65]. 
Tobacco Use: The Smoking History Questionnaire (SHQ)[66] is a measure of smoking history and 
patterns. The Questionnaire for Smoking Urges-Brief (QSU-Brief) [67, 68] is a 10-item measure that evaluates 

the structure and function of smoking urges. The QSU-Brief has very good reliability (=.78–.89).The 
Fagerström Test for Nicotine Dependence (FTND) [69] is a 6-item self-report measure of nicotine dependence, 
with good internal consistency and test-retest reliability [69, 70]. Smoking outcomes will include a self-report of 
the number of cigarettes smoked, verified by carbon monoxide (CO) breath tests (< 8 ppm) [71]. Periods of 
sustained continuous abstinence and survival time to lapse and relapse will also be analyzed. Lapse will be 
defined as an episode of smoking that interrupts continuous abstinence, and a relapse is a return to regular 
smoking [72, 73]. A Timeline Follow-back (TLFB) procedure will be used to assess time to first smoking lapse 
and time to first relapse, defined as the seventh day after quit date on which smoking occurs [74]. The 
Contemplation Ladder is an 11-point self-report measure of readiness to quit smoking. It has good predictive 
and concurrent validity with the likelihood of a serious quit attempt within 6 months [75]. 
 
Social, Occupational, Mental Health and Physical Functioning: The Short Form 36 Health Survey (SF-
36) is a 36-item self-report measure of current physical, mental health, and social functioning [76, 77], with 
excellent psychometric properties [76]. The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-
Q) [78, 79] is a commonly used self-report measure to assess quality of life in several domains: general 
activities, physical health, subjective feelings, leisure time activities, social relationships, work, and household 
duties. The Smoking Cessation Quality of Life Questionnaire (SCQoL) is a self-reported measure designed to 
quantify to quantify the impact of smoking cessation on perceived functioning and well-being [80]. The 
Sheehan Disability Scale (SDS) is a reliable and valid 3-item self-report measure of overall disability, and 
assesses social life, work/study, and family life functioning [81]. The Work and Social Adjustment Scale 
(WSAS) is a 5-item measure of leisure activities, relationships, and home and work functioning [82].  
 
Psychiatric Symptoms: The PTSD Checklist  for DSM-5 (PCL-5) is a popular 20-item measure of PTSD 
symptoms [83]. The Beck Depression Inventory (BDI-II) is a 21-item measure of depression severity [84]. 
 
Process Measures: Experiential avoidance will be measured with the Acceptance and Action 
Questionnaire (AAQ)[85], a 7-item self-report measure of emotional avoidance and inaction. The Mindful 
Attention Awareness Scale (MAAS) is a 15-item scale of the ability to mindfully observe the present moment 
[86]. The Valued Living Questionnaire is a self-report measure of the extent to which a person is living in 
accordance with one’s values in everyday life [87]. All measures possess good internal consistency, and 
construct validity. These measures will be used for mediation analyses in the future clinical trial.  
 
Treatment Satisfaction: Client Satisfaction Questionnaire-8 (CSQ-8; [88]): This 8-item scale measures 
patients’ perceived satisfaction with treatment and has good internal consistency (=.83-.93) [89]. The CSQ 
will be administered at the end of treatment (Session 10). 
 
Retention and Noncompletion. We will use several strategies to increase retention: 1) We will ask 
participants to provide contact information and a release of information for people who will know how to get in 
touch with the participant; 2) We will call participants and remind them about their appointments, 3) We will pay 
participants for their time and travel for sessions and follow-up assessments. We will interview participants to 
determine reasons for study withdrawal and provide referrals for other services. 
Data Management and Statistical Analysis. Participant files will be kept in a locked cabinet and data files 
will be password-protected and encoded with ID numbers. IDs will be unrelated to any identifying information. 
Data will be checked for values out of the normal range, inconsistencies, omissions and errors.  
Preliminary analyses and handling missing data. Chi square and t-tests or non-parametric equivalents 
will be used to compare demographics, and baseline levels of tobacco dependence, PTSD severity, functional 
impairment, and motivation to quit smoking in both groups. If differences are detected, we will consider using 
these variables as covariates in subsequent analyses. To better characterize missing data, we will attempt to 
gather follow-up information for dropouts. If analyses show major differences between Veterans who complete 
the study or drop-out, we will explore methods for imputing data, and stratify analyses based on any bias [90].  
 
Primary analyses. Primary analyses will involve examination of the feasibility and acceptability of a RCT 
of ACT-PT. Feasibility will be verified by adequate 1) recruitment rates (i.e., 3 Veterans per month), 2) >90% 
fidelity of clinician adherence to the treatment protocol, and 3) data retention (i.e., ≥70% of participants who 
attend at least 8 sessions of ACT-PT or FFS. An acceptable level of attrition will be ˂30% in each condition. 
We will also evaluate the number of ACT-PT and FFS sessions attended, by comparing the percentage of 
Veterans in each condition attending at least 80% of sessions (8/10). We will also examine the willingness of 
Veterans to be randomized with a goal of 80% of those approached who agree to randomization, the number 
of referrals from clinicians, ease of recruitment based on the average number of contacts needed to get 
consent and to schedule visits, the number of eligible participants from the pool of potential participants, and 
adherence and compliance to the treatment protocol (both counseling and nicotine patch) by comparison with 
the theoretical complete compliance. We will compare Veteran acceptability between groups by conducting an 

independent samples t-test on the CSQ-8 [88]. We will compare attrition rates (<15% vs. >15%) between the 
two groups using a chi square and logistic regression analysis. We will also obtain qualitative data about the 
acceptability of the ACT-PT and FFS treatments.  
 
Secondary analyses. Efficacy is not our major analytic aim, given the preliminary nature of this study [13]. 
We will examine differences in measures of tobacco use, PTSD severity and quality of life to identify empirical 
targets for further refinement of the treatment and inform the design of the future Merit Review. We will 
examine group differences for biologically verified abstinence, duration of sustained continuous abstinence and 
time to lapse and relapse [91, 92]. Based on the intent-to-treat principle, all participants randomized to 
treatment will be included in analyses. We will also look at individual trajectories of response to gain better 
insight into which participants do particularly well (or poorly) in the two interventions. Effect sizes and 95% 
confidence intervals will be used as only one element to estimate power and sample size to help plan for a 
Merit Review study [13].  In addition, we will explore differences in treatment groups over time using HLM [93] 
(time x condition) on other outcomes of interest, including PTSD symptoms, functioning and health-related 
quality of life. We will also examine the effects of treatment on the potential mediators (i.e., process variables), 
and the effect of these mediators on treatment outcome to identify candidate mediators for future study. 
 
Power analysis. Given the caveats of Leon et al. [13], our primary outcome(s) are feasibility and 
acceptability. Consistent with the recommended stage model for behavioral therapy development [13, 14], the 
aim of this stage 1b pilot study is to inform future treatment development and evaluation plans. We expect 
ACT-PT will produce a medium treatment effect. In order to have .80 power to detect differences at a two-tailed 
alpha level of .05, a medium effect would require n=125. This is beyond the scope of a SPiRE, and more 
appropriate for a stage II trial. A total sample size of 50 (25 per cell) is feasible and consistent with the 
recommendation of 15-30 participants per condition for a stage 1b study [14].