A Puff Topography Biofeedback Paradigm to Reduce Stress-Precipitated Smoking Reinforcement
Phase: NA
Conditions: Cigarette Smoking
Sponsor: Rutgers, The State University of New Jersey

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 0 of 28 
 
 
 
 
 
 
A Puff Topography Biofeedback Paradigm to Reduce Stress-
Precipitated Smoking Reinforcement 
NCT05644002 
Document Date: 05/02/2023 
 
 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 1 of 28 
 
 
INTERVENTIONAL 
RESEARCH PROTOCOL TEMPLATE 
(HRP-503a) 
 
 
 
 
STUDY INFORMATION 
 
▪ 
Title of Project: Development of a Puff Topography Biofeedback Paradigm to Reduce 
Smoking Reinforcement 
 
▪ 
Principal Investigator Names 
Teresa Leyro, Ph.D. 
Samantha Farris, Ph.D. 
 
▪ 
Principal Investigator Div. & Dept. 
Department of Psychology 
 
▪ 
Principal Investigator Contact Info:  
Room 539, Tillett Hall, 53 Avenue E., Piscataway, NJ 08854  
Dr. Leyro: 848-445-2090, teresa.leyro@rutgers.edu 
Dr. Farris: 848-445-2174, samantha.farris@rutgers.edu 
 
▪ 
Protocol Version and Date: 
V21    05/02/2023  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 2 of 28 
 
 
 
Table of Contents 
Skip To Section: Hold CTRL + Click (Below) To Follow Link in Blue 
 
1.0 
Research Design 
 
 
1.1 
Purpose/Specific Aims 
 
 
1.2 
Research Significance 
 
 
1.3 
Research Design and Methods 
 
 
1.4 
Preliminary Data 
 
 
1.5 
Sample Size Justification 
 
 
1.6 
Study Variables 
 
 
1.7 
Drugs/Devices/Biologics 
 
 
1.8 
Specimen Collection 
 
 
1.9 
Data Collection 
 
 
1.10 
Timetable/Schedule of Events 
 
 
2.0 
Project Management 
 
 
2.1 
Research Staff and Qualifications 
 
 
2.2 
Research Staff Training 
 
 
2.3 
Resources Available 
 
 
2.4 
Research Sites 
 
 
3.0 
Multi-Center Research 
 
 
4.0 
Subject Considerations 
 
 
4.1 
Subject Selection and Enrollment Considerations 
 
 
4.2 
Secondary Subjects 
 
 
4.3 
Number of Subjects 
 
 
4.4 
Consent Procedures 
 
 
4.5 
Special Consent Populations 
 
 
4.6 
Economic Burden and/or Compensation For Subjects 
 
 
4.7 
Risks of Harm/Potential for Benefits to Subjects to Subjects 
 
 
5.0 
Special Considerations 
 
 
5.1 
Health Insurance Portability and Accountability Act (HIPAA) 
 
 
5.2 
Family Educational Rights and Privacy Act (FERPA) 
 
 
5.3 
Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations) 
 
 
5.4 
General Data Protection Regulation (GDPR) 
 
 
5.5 
 NJ Access to Medical Research Act (Surrogate Consent)  
 
 
6.0 
Data Management Plan 
 
 
6.1 
Data Analysis 
 
 
6.2 
Data Security 
 
 
6.3 
Data Safety And Monitoring 
 
 
6.4 
Reporting Results 
 
 
6.5 
Secondary Use of the Data 
 
 
7.0 
Research Repositories – Specimens and/or Data 
 
 
8.0 
Approvals/Authorizations 
 
 
9.0 
Bibliography 
 
 
 
 
 
 
 
 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 3 of 28 
 
 
 
1.0 Research Design 
 
1.1 Purpose/Specific Aims 
 
A.  Objectives  
In the current study we propose a proof-of-concept experimental test of PTBT and its ability to modify 
stress-precipitated puff topography, and in turn, acute smoking reinforcement. Specifically, 
emotionally-distressed daily smokers (N=88) will be randomized to either PTBT or Control (Sham) 
Training. After the training day, participants will complete a stress-precipitated smoking trial where 
they will undergo an acute laboratory stress induction and smoke using the assigned training. We 
propose the following specific aims:  
Aim 1 (Target Engagement): To evaluate PTBT as a strategy to “engage” (modify) puff 
topography -- a putative biobehavioral target of smoking reinforcement. Following stress-
induction, we hypothesize that PTBT, compared to Control, will result in significant changes in puff 
topography, namely: (a) smaller average puff volume (mL), (b) shorter average puff duration (sec), 
and (c) longer inter-puff intervals (sec).  
Aim 2 (Acute Clinical Outcomes): To evaluate whether PTBT produces acute clinical changes in 
stress-precipitated smoking reinforcement. Following stress-precipitated smoking trial, we 
hypothesize that PTBT, compared to Control, will result in significantly less acute smoking 
reinforcement, indexed by: (a) greater reductions in expenditures and consumption of hypothetical 
cigarettes smoked within the same context (e.g., PTBT or ad-lib) and (b) lower self-report cigarette 
satisfaction/reward (self-report) post-smoking.    
Aim 3 (Explore Mechanisms of PTBT). To explore cardiac vagal control (CVC) as a biological 
mechanism of PTBT. We will explore whether there are differences in CVC (respiratory sinus 
arrythmia) between smokers in PTBT compared to Control. We hypothesize that PTBT (vs Control), 
will produce greater reductions in CVC, as compared to baseline CVC, during stress-precipitated 
smoking. 
This is the first study to test whether an integrated theoretically-based biobehavioral paradigm can 
modify puff topography and subsequent smoking reinforcement. This addresses the need for 
innovative approaches to decrease acute smoking reinforcement.  If associated with reduced 
smoking reinforcement, this paradigm could inform pre-cessation efforts designed to better prepare 
emotionally-distressed smokers for quitting. 
 
 
 B.  Hypotheses / Research Question(s) 
Smoking among adults with emotional distress is a recognized tobacco health disparity. Smokers with 
emotional distress are particularly vulnerable to smoking reinforcement due to various 
biopsychological factors that contribute to deficits in emotion regulation and reward processing, which 
undermine cessation efforts. Better preparing smokers for cessation (prior to a quit attempt) is essential 
to improve outcomes in emotionally-distressed smokers who require additional coping strategies to 
address affect-driven smoking.  
A critical driver of smoking reinforcement is HOW a cigarette is smoked (i.e., puff topography). The 
timing and intensity of one’s puffing can titrate or maximize the cigarette’s rewarding effect. Our group 
has identified puff topography as a novel biobehavioral “target” mechanism of smoking 
reinforcement in emotionally-distressed smokers. We have found that topographical components of 
puffing (e.g., shorter inter-puff intervals, longer puff durations) are linked to heightened smoking 
reinforcement in emotionally-distressed smokers, but not in control smokers. Emotionally-distressed 
smokers also take larger and more rapid initial puffs at the start of a cigarette – maximizing immediacy 
and intensity of reward.  
Although largely considered a behavioral phenotype of smoking reinforcement, inherent in puffing 
behavior are corresponding changes in cardiorespiratory parameters (e.g., cardiac vagal control [CVC]) 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 4 of 28 
 
 
that may promote self-regulation and reduce craving. We recently proposed an integrated 
psychophysiological model of emotional distress and smoking, wherein impaired smoker CVC not only 
implicates physiological homeostasis, but also influences addiction-relevant processes, including 
impaired higher-order cognitive processes needed for self-regulation and psychological functioning 
(e.g., reduced anxiety and stress). Yet, under certain time-sensitive contexts (e.g., stress), emotionally-
distressed smokers may puff in a way that enhances CVC, resulting in acute self-regulatory benefits, 
and in turn paradoxically amplify the reinforcing value of each puff. Thus, a biobehavioral intervention 
that could “engage” (modify) puff topography has the strong potential to reduce the reinforcing value of 
cigarettes in emotionally-distressed smokers. 
Informed by our biobehavioral framework, we developed a Puff Topography Biofeedback Training 
(PTBT), a modified application of heart rate variability biofeedback to change puff topography. PTBT is 
a 30-min training that teaches smokers to adjust their puffing to a pace that is designed to minimize 
CVC in order to attenuate acute self-regulatory, emotional, and craving-reductions associated with 
smoking. Thus, PTBT is a theoretically-informed, well-specified paradigm designed to directly target 
puff topography – a mechanism of smoking reinforcement, which directly aligns with the NIH’s Science 
of Behavior Change (SOBC) and experimental therapeutics initiatives.  
 
 
1.2 Research Significance  
1. This is the first study to develop and test a puff topography biofeedback training (PTBT). Participants 
will receive real-time feedback regarding puffing (e.g., when to inhale/exhale, breath duration, and inter-
puff interval). PTBT was designed based on an integrated theoretical behavioral and psychophysiological 
model of smoking reinforcement, and thus aims to address learning-based behavioral aspects of puffing 
(by promoting extinction learning/new learning), in addition to altering a physiological mechanism of puffing 
(CVC). Therefore, PTBT is a promising theoretically-based intervention, that if supported by this proposed 
experimental study, would be well-positioned for progressive translation into intervention efficacy testing, 
consistent with NIH initiatives.49–51   
2. There is increasing recognition that preparing smokers for cessation (prior to a quit attempt) is essential 
to improve outcomes,52 particularly in smokers with emotional distress who may require additional coping 
strategies to address affect-driven smoking.53 If PTBT is associated with reduced smoking reinforcement, 
this paradigm could inform treatment effects designed to prepare emotionally-distress smokers for 
quitting.52 Notably, existing interventions that successfully attenuate pre-cessation smoking reinforcement 
are primarily pharmacological in nature (e.g., nicotine replacement,54 varenicline55), while behavioral 
interventions targeting smoking reinforcement are generally used during the post-cessation period (e.g., 
contingency management,56 behavioral activation/behavioral economic-based approaches57). Thus, the 
current study would address a gap in the provision of evidence-based behavioral interventions that target 
pre-cessation smoking reinforcement, which has the potential to improve cessation outcomes in 
vulnerable smokers (emotionally-distressed).  
 
 
1.3 Research Design and Methods 
This study is an experimental, between-subjects test of biofeedback puff topography training (relative to 
sham training) in reducing stress-induced smoking reinforcement. Specifically, combustible cigarettes 
smokers (n = 80) will be randomized to receive puff topography biofeedback (n = 40) or sham training (n = 
40) prior to exposure to a laboratory stressor paradigm. Stress-precipitated smoking behavior will be 
assessed directly after the stressor task, wherein participants will be given the instructions to smoke utilizing 
their assigned puff training. Smoking reinforcement will be measured using a multi-method approach, 
including self-report, psychophysiology, and behavioral indices (see Measures). Outcome variables 
include: (1) puff topography indices (averages, trajectory) and (2) reinforcer pathology indices (delay reward 
discounting, cigarette demand, urges, affect, and smoking enjoyment). 
 
A. Research Procedures 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 5 of 28 
 
 
See Figure 3 for an overview of the experimental procedures. Participants will complete a 
telephone interview to verify key exclusion/inclusion criteria. Participants who appear to be 
eligible will be scheduled for a remote assessment session. If eligible following the remote 
session, participants will be scheduled for two in-person visits on consecutive days. For 
standardization (internal validity), all in-person visits will be scheduled to occur ~4hrs following 
the estimated time of participants’ first cigarette of the day. Participants will be informed that they 
will smoke their second daily cigarette during the lab visit and instructed to avoid behaviors that 
may confound CVC (e.g., vigorous physical activity or consumption of caffeine within 2 hr; alcohol 
use within 12 hr).  
 
Baseline Assessment (Remote Visit): Staff will obtain written informed consent, after which 
participants will complete an eligibility assessment (see Table 1). They will then complete the 
baseline assessment battery (see Table 1).  
Training Visit (V1): Participants will be screened for final eligibility criteria (e.g., CO level) upon 
arrival. Assessment of self-reported affective and smoking related variables will be conducted via 
self-report at various times throughout the session (see the orange stars on Figure 3). 
Participants will be attached to physiological recording equipment throughout the session, 
including blood pressure volume, ECG, and respiration. When they smoke (in a ventilated 
smoking room), smoking topographical indices will be recorded using the handheld Clinical 
Research Support System (CReSS micro; described in C.7).  
Training Conditions: Eligible participants will then be randomized to either the PTBT or Control 
(Sham Training) and informed that the training will be used in V2. Block randomization will be 
used with biological sex (female vs. male) as a blocking variable, as sex is a known factors that 
influences puff topography and reinforcement.36,58,59  Both trainings will be time-matched.  
PTBT: PTBT is designed to decrease puff topography influences on smoking reward informed by 
heart rate variability biofeedback paradigms. Participants will be taught how to puff in a way that 
may feel different from their usual puffing behavior. Participants will be hooked up to a respiratory 
band, electrocardiogram (ECG) electrodes, and a blood volume sensor finger cuff (pulse 
plethysmograph) while seated in a ventilated smoking room. Following a 5-min adaptation period, 
they will be introduced to a breathing pacer (EZ-Air Plus; Biofeedback Foundation of Europe), 
which is integrated with the Thought Technology biofeedback interface (Figure 4), and taught 
how to use the pacer to guide the pace of their inhalation and exhalation. Participants will be 
taught to breathe steadily as a white 
ball (pacer) proceeds up the incline, 
and exhale as they follow the ball on 
the decline. They will first practice 
breathing normally with the pacer to 
ensure they understand the 
procedures. Then, participants will 
smoke following the pacer while using 
the CReSS micro device for a 5-min 
phase. To address reinforcement 
immediacy and intensity, the pacer 
will be set to a 2 sec inhalation 
matched with a 2 sec exhalation, for a 
4 sec cycle, such that puffing maps 
onto a respiration pace of 15 breathes/min. This pace should minimize CVC (Figure 2, right). To 
address reinforcement reliability, the inter-puff-interval will vary between 4 secs and 30 secs as 
the experimenter will instruct the participant when to puff. In an adjacent room, the experimenter 
will be able to monitor real-time displays of physiological data and observe the session via video 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 6 of 28 
 
 
conferencing system and provide additional training instructions, as needed. Participants will then 
complete a 5-min rest period.  
Control: In the control condition, i.e. sham training, participants will be hooked up to the same 
physiological monitoring equipment and complete the same 5-min adaptation period. They will 
then be instructed to smoking with the CreSS device while focusing their attention during a 5-min 
vanilla task.66 The task involves attending to a computer screen and counting the number of times 
a designated color rectangle occupies the screen. Different colored rectangles are presented one 
at a time, for 500ms every 10 sec, for a total of 5-min. The full color spectrum is reflected and 
participants are told to make their best guess about color match. Participants are asked at the 
end to report the number of times the designated color was observed and are not given any 
feedback or incentive for correct color counts. No instructions will be provided about puffing 
behavior. Participants will then complete a 5-min rest period.  
Stress-Precipitated Smoking Visit (V2). Participants will return to the laboratory on the following 
day, at the same time, and be provided the same pre-visit instructions. Participants will be hooked 
up with physiological monitoring assessment while seated in the smoking lab. Next, a new consent 
will be presented, introducing them to the Trier Social Stress Test (TSST), which has been used in 
our prior studies (R03DA041556; F31DA043934). The TSST is a well-validated laboratory 
paradigm that reliably induces psychological and physiological stress,67–69 including smoking 
craving.70,71 While presenting the consent form, the experimenter will explain that they will have to 
prepare for and deliver a speech about why they are the best candidate for a job of their choosing. 
To maximize anticipatory stress, participants will be introduced to a male and female confederate 
who will presumably observe and evaluate the speech.72 After a 2-min preparation period, they will 
be shown a video example of a speech where a participant receives negative/neutral feedback 
from confederates, which serves to provide participants with additional information regarding the 
stressful nature of the task. In our studies, this preparation/anticipatory period produces medium-
large increases in negative affect in smokers (Cohen’s d = 0.60-1.30). After the preparation period, 
participants are told that the confederates need additional time to trouble-shoot the camera system, 
and as a result they will be able to smoke before delivering the speech. Participants will be 
instructed that they will practice the training they learned (PTBT or Control) while they smoke, and 
will complete the same 5-min adaptation period pre-smoking and 5-min rest period post-smoking. 
The stress-precipitated smoking trial will be followed by the post-smoking assessments. 
Participants will then be unhooked from the physiological monitoring equipment and informed that 
they do not actually have to give the speech. The research staff will proceed to notify participants 
that they have completed the study visit.  Research staff will thank participants for all of their time 
and effort, provide them with their respective compensation, and encourage them to contact the 
study staff via email or phone (contact information listed on the participant’s previously provided 
consent form) should they have any additional questions or concerns regarding their participation.  
B. Data Points 
Group differences will be examined between biofeedback puffing vs. shame in response to V2 
stress-precipitated smoking through measures of: (1) puff topography indices (puff volume, 
duration, IPI), (2) self-report assessments and (3) physiological indices of emotional distress 
(cardiac vagal control). 
 
C. Study Duration 
This study comprises one remote session of up to two hours, and two in-person visits over the 
course of two days, with a duration of up to 2 hours for V1 and V2 respectively.  
 
D. Endpoints 
The endpoint of the study is post-V2, once participants have completed the experimental design of 
the second visit (assuming eligibility through V1).  
 
1.4 Preliminary Data 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 7 of 28 
 
 
1. Smoking among adults with emotional distress is a recognized tobacco health disparity.1–3 
Despite reductions in the prevalence of smoking over the past fifty years (currently ~15% in US),4,5 smoking 
prevalence in individuals with emotional distress (i.e., anxiety and mood disorders) is disproportionally 
higher (38%-45%)2,6,7 and has remained relatively stable over recent years.2 Smokers with emotional 
distress (vs. those without) are less likely to quit smoking successfully8–13 in large part because of the 
reinforcing effects of cigarettes (i.e., smoking reinforcement).14,15 Incentive sensitization theory30 
proposes three core processes that underlie drug reinforcement: liking, wanting, and learning. Smoking is 
posited to be initially motivated by the positive reinforcing effects of cigarettes/nicotine (i.e., “liking”: 
pleasure, satisfaction) and in turn, appetitive and urgency (“wanting”: craving) motivation for cigarettes 
develops due to the reliable, immediate rewarding effect.16 Over time, smoking is maintained by the 
negative reinforcing effects (i.e., “learning”: relief from aversive states and stress).15,17 Smokers with 
emotional distress are particularly vulnerable to smoking reinforcement due to various biopsychological 
factors that contribute to deficits in emotion regulation and heightened reward processing.18–25 Thus, there 
is an ongoing need for innovative approaches to decrease smoking reinforcement to improve cessation 
success in this vulnerable group.  
2. A critical aspect of smoking reinforcement is the reliability, intensity, and immediacy of its 
rewarding effect.26 We propose that these aspects of smoking reinforcement are particularly valuable to 
emotionally-distressed smokers who rely on cigarettes as a go-to “quick fix” strategy during certain time-
sensitive contexts (e.g. acute distress, or initial smoking abstinence). For example, modification of WHEN 
they smoke (e.g., when stressed) and HOW they smoke their cigarette provides smokers with the ability to 
easily titrate/maximize the timing and intensity of the cigarette’s rewarding effect. These aspects of smoking 
behavior are referred to as “puff topography”, which can be indexed in many ways including puff volume 
(amount of carbon monoxide [CO] inhaled, mL), puff duration (length of time for each inhalation, sec), and 
inter-puff interval (time between inhalations, sec). Indeed, evidence indicates that both trait and state 
distress are related to alterations in smoking behavior. For example, smokers with emotional distress 
(compared to those without) smoke in a way that maximizes intensity (e.g., larger inhalations while 
puffing).27,28 
3. Puff topography is a novel “target” of smoking reinforcement in emotionally-distressed smokers. 
Although puff topography has been historically studied in the context of tobacco control (i.e., reducing CO 
or nicotine exposure),29–33 we propose puff topography as a biobehavioral target of smoking 
reinforcement. We have found that topographical components of puffing (e.g., shorter inter-puff intervals, 
longer puff durations) are linked to heightened smoking reinforcement (wanting, liking) in emotionally-
distressed smokers but not control smokers (small-medium effects).34 We have also identified several 
cognitive-affective aspects of emotional distress (e.g., distress intolerance, negative urgency) that are 
related to alterations in ad-libitum and stress-precipitated puff topography.35–38 Notably, we have moved 
beyond the status quo in our approach to this work by examining puff-to-puff changes (time-varying) during 
smoking rather than relying on the established (normative) methods of examining average puff 
parameters.28,39,40 This method provides precision in understanding time-sensitive aspects of puff 
topography. For example, we found that emotionally-distressed smokers (vs. non-distressed) take larger 
and more rapid initial puffs at the start of a cigarette (i.e., reward immediacy and intensity) and demonstrate 
more persistent, stable puffs over the course of the cigarette (i.e., reward reliability).35 Together, our data 
indicate that puff topography is a well-specified, precise, time-sensitive mechanism of smoking 
reinforcement. If puff topography can be “engaged” via intervention (modifiable), it would have the strong 
potential to reduce the reinforcing value of cigarettes in emotionally-distressed smokers. 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 8 of 28 
 
 
4. An integrated psychophysiological framework to understanding puff topography (Figure 1). 
Inherent in puffing behavior are corresponding 
changes in cardiorespiratory parameters, such 
as cardiac vagal control (CVC), i.e., vagus 
nerve mediated regulation of the heart rate. 
Changes in heart rate that occur during 
inhalation and exhalation (i.e., respiratory sinus 
arrhythmia [RSA]) reflect CVC. When breathing 
is slowed to a pace that maximizes oscillations in 
heart rate and blood pressure (increased CVC),41 
there are numerous clinical benefits,42 including 
improved self-regulation, mediated by changes 
in prefrontal-subcortical inhibitory circuits.43,44 
Indeed, improved CVC promotes more flexible 
and adaptive responding to the environment and 
less hypervigilance to threat.45 In accord, we 
recently 
proposed 
an 
integrated 
psychophysiological model of emotional distress and smoking46 wherein impaired CVC observed in 
smokers is not only implicated in physiological homeostasis, but also in addiction-relevant processes, 
including higher-order cognitive processes needed for self-regulation46 and psychological functioning (e.g., 
distress).43 Although slowed breathing to improve CVC is often leveraged for clinical benefit, we posit that 
under certain time-sensitive contexts (e.g., stress), emotionally-distressed smokers puff in a style that 
mimics slowed breathing – maximizing oscillations in cardiorespiratory systems and acute self-regulatory 
benefits – which in turn, paradoxically enhance smoking reinforcement. Thus, we propose that puff 
topography is not only a behavioral determinant of smoking reinforcement, but is also physiologically-based 
(CVC), and together drive the reinforcing value of each puff.  
5. Puff Topography Biofeedback Training (PTBT) as a novel strategy for “target engagement”. CVC’s 
effect on self-regulation has been leveraged in biobehavioral interventions, like heart rate variability 
biofeedback, which has been used to promote reductions in emotional distress43 and substance craving.47 
Heart rate variability biofeedback involves instructing individuals to slow their respiration rate to around 6.0 
breaths/minute,41 by following a breathing pacer and/or viewing real-time respiration and heart rate wave 
forms, with the goal of achieving wave form synchrony. See Figure 2 for an illustration of how breathing 
changes can influence CVC (i.e., Min/Max) by creating synchrony vs. asynchrony between heart rate (red) 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 9 of 28 
 
 
and respiration (green), and in turn theoretically influence reinforcement. Aligned with our proposed 
framework, we developed Puff Topography Biofeedback Training (PTBT), a modified application of heart 
rate variability biofeedback, to change puff topography. Specifically, PTBT involves teaching emotionally-
distressed smokers to adjust their puffing to a pace that produces asynchrony between heart rate and 
respiration, in order to attenuate CVC and self-regulatory, emotional, and craving-reductions associated 
with smoking. Aligned with the NIH’s Science of Behavior Change inititiave48 and experimental medicine 
approach,49 in the current study we propose to test whether the identified target (i.e., puff topography) 
can be experimentally engaged via a well-specified intervention (PTBT).  
 
 
1.5 Sample Size Justification 
The effects of PTBT on the outcomes of interest are unclear given that there are no prior data. However, 
our studies of differences in puff topography in the context of acute stress vs. control produce medium-
sized effects (ds=0.46-0.54).36 Thus, we believe a medium size effect is clinically meaningful, and 
therefore, the sample size was calculated to detect a medium effect size difference across training 
groups. Mean Difference. For linear regression models, a sample size of 58 is sufficient to detect a 
medium effect size (f2=.143 [R2 change/1-cumulative R2) = .143) with 80% power and alpha of 0.05 via 
multiple regression analyses with up to 10% variance explained by the main predictor (training group) and 
up to 5 other covariates (e.g., sex, number of cigarettes per day, depressive/anxiety symptom severity, 
corresponding baseline values, and CO boost) accounting for up to additional 20% of the anticipated 
variance. Without any covariates in the model, a sample size of 73 is needed to detect a medium effect 
size (f2=.11) across training groups (explaining 10% variance). Mediation (Aim 3). Statistical power for a 
mediation analysis with a single mediator was estimated using Monte Carlo power analysis for indirect 
effects.86 The inclusion of mediation analyses led us to increase our sample size to n=80, which is 
sufficient for detection of indirect effects with a proportion-mediated effect size of 50%87 (correlations 
between predictor, mediators, and outcome, r =.40-.43) with 80% power and alpha of 0.05. which we 
deemed sufficient given the exploratory nature of these analyses. Taken together, to ensure analyses are 
adequately powered, we propose a sample of 88 (allowing for ~8-10% attrition) with a final intended 
sample of 80 completers (40 per condition). 
 
1.6 Study Variables 
 
A.   Independent Variables, Interventions, or Predictor Variables  
1. Training Conditions: Eligible participants will then be randomized to either the Puff Topography 
Biofeedback (PTBT) or Control (Sham Training) and informed that the training will be used in V2. Block 
randomization will be used with biological sex (female vs. male) as a blocking variable, as sex is a known 
factors that influences puff topography and reinforcement.36,58,59  Both trainings will be time matched. 
PTBT: PTBT is designed to decrease puff topography influences on smoking reward informed by heart rate 
variability biofeedback paradigms. Participants 
will be taught how to puff in a way that may feel 
different from their usual puffing behavior. 
Participants will be hooked up to a respiratory 
band, electrocardiogram (ECG) electrodes, 
and a blood volume sensor finger cuff (pulse 
plethysmograph) while seated in a ventilated 
smoking room. Following a 5-min adaptation 
period, they will be introduced to a breathing 
pacer (EZ-Air Plus; Biofeedback Foundation of 
Europe), which is integrated with the Thought 
Technology biofeedback interface (Figure 4), 
and taught how to use the pacer to guide the 
pace of their inhalation and exhalation. 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
Page 10 of 28 
 
 
Participants will be taught to breathe steadily as a white ball (pacer) proceeds up the incline, and exhale as 
they follow the ball on the decline. They will first practice breathing normally with the pacer to ensure they 
understand the procedures. Then, participants will smoke following the pacer while using the CreSS micro 
device for a 5-min phase. To address reinforcement immediacy and intensity, the pacer will be set to a 2 
sec inhalation matched with a 2 sec exhalation, for a 4 sec cycle, such that puffing maps onto a respiration 
pace of 15 breathes/min. This pace should minimize CVC (Figure 2, right). To address reinforcement 
reliability, the inter-puff-interval will vary between 10 secs and 30 secs, as the experimenter will instruct the 
participant when to puff. In an adjacent room, the experimenter will be able to monitor real-time displays of 
physiological data and observe the session via video and intercom system and provide additional training 
instructions, as needed. Participants will then complete a 5-min rest period.  
Control: In the control condition, i.e. sham training, participants will be hooked up to the same physiological 
monitoring equipment and will complete a 5-min adaptation period. They will then be instructed to smoking 
with the CreSS device while focusing their attention during a 5-min vanilla task.66 The task involves 
attending to a computer screen and counting the number of times a designated color rectangle occupies 
the screen. Different colored rectangles are presented one at a time, for 500ms every 10 sec, for a total of 
5-min. The full color spectrum is reflected and participants are told to make their best guess about color 
match. Participants are asked at the end to report the number of times the designated color was observed 
and are not given any feedback or incentive for correct color counts. No instructions will be provided about 
puffing behavior. Participants will then complete a 5-min rest period. 
2.  Stress-Precipitated Smoking Visit (V2). Participants will return to the laboratory on the following day, 
at the same time, and be provided the same pre-visit instructions. Participants will be hooked up with 
physiological monitoring assessment while seated in the smoking lab. Next, a new consent will be 
presented, introducing them to the Trier Social Stress Test (TSST), which has been used in our 
prior/ongoing studies (R03DA041556; F31DA043934). The TSST is a well-validated laboratory paradigm 
that reliably induces psychological and physiological stress,67–69 including smoking craving.70,71 While 
presenting the consent form, the experimenter will explain that they will have to prepare for and deliver a 
speech about why they are the best candidate for a job of their choosing. To maximize anticipatory stress, 
participants will be introduced to a male and female confederate who will presumably observe and evaluate 
the speech.72 After a 2-min preparation period, they will be shown a video example of a speech where a 
participant receives negative/neutral feedback from confederates, which serves to provide participants with 
additional information regarding the stressful nature of the task. In our studies, this preparation/anticipatory 
period produces medium-large increases in negative affect in smokers (Cohen’s d = 0.60-1.30). After the 
preparation period, participants are told that the confederates need additional time to trouble-shoot the 
camera system, and as a result they will be able to smoke before delivering the speech. Participants will 
be instructed that they will practice the training they learned (PTBT or Control) while they smoke and will 
complete the same 5-min adaptation period pre-smoking and 5-min rest period post-smoking as in V1. The 
stress-precipitated smoking trial will be followed by the post-smoking assessments. Participants will then 
be unhooked from the physiological monitoring equipment and informed that they do not actually have to 
give the speech. The research staff will then proceed to notify participants that they have completed the 
study visit. Research staff will thank participants for all of their time and effort, provide them with their 
respective compensation, and encourage them to contact the study staff via email or phone (contact 
information listed on the participant’s previously provided consent form) should they have any additional 
questions or concerns regarding their participation. 
 
B.  Dependent Variables or Outcome Measures  
Acute Clinical Outcomes: Smoking Reinforcement.  
Short Hypothetical Cigarette Purchase Task (S-CPT) 
Modified Cigarette Evaluation Questionnaire (mCEQ) 
 
Target Mechanisms: Cardiac Vagal Control. 
Respiratory Sinus Arrythmia (RSA) 
 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
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Target: Puff Topography (CreSS Micro).  
Puff Volume (mL) 
Puff Duration (seconds) 
Inter-Puff-Interval (IPI; seconds) 
 
C. Eligibility Measures 
Medical History Form (MHF) 
 
The Mini International Neuropsychiatric Interview 7.0.0 (MINI) sections C, I, J, and K. 
Expired CO Breath Sample 
Smoking History Questionnaire (SHQ)  
Fagerström Test for Cigarette Dependence (FTCD) 
 
1.7 Drugs/Devices/Biologics  
N/A. 
 
1.8 Specimen Collection 
N/A. 
 
1.9 Data Collection 
 
A. Primary Data Collection 
▪ 
Location: This project will be conducted at the Rutgers University Affective and Biological 
Underpinnings of Substance Use and Anxiety (ABUSA) Laboratory located on the 2nd floor of 
1 Spring Street, New Brunswick, NJ. The lab space is equipped with two rooms for 
psychophysiological assessment with adjacent rooms for monitoring, an in-lab smoking room 
that is ventilated to the outdoors with an adjacent control room for monitoring. Some eligibility 
and baseline assessments will be conducted remotely, using video-conferencing software 
(e.g., HIPAA compliant Zoom or Teams platforms) and online survey collection software (e.g., 
Qualtrics).  
▪ 
Process of Data Collection: Data will be collected by IRB-approved and trained research 
staff from both labs of the Principal Investigators, in accordance with the procedures described 
in detail in section 1.3. In brief, combustible cigarettes smokers with emotional distress (N=88) 
will be randomized to receive puff topography biofeedback (n = 44, 50%) or sham training (n = 
44, 50%) prior to exposure to a laboratory stressor paradigm. Stress-precipitated smoking 
behavior will be assessed directly after the stressor task, wherein participants will be given the 
instructions to smoke utilizing their assigned puff training. Smoking reinforcement will be 
measured using a multi-method approach, including self-report, psychophysiology, and 
behavioral indices 
▪ 
Timing and Frequency: After the initial telephone screening, data collection will occur on one 
remote occasion and two in-person occasions. The remote session entails one initial 
assessment to confirm eligibility and collection of baseline data via interview and self-report. 
For the in-person visits, V1 entails data collection through self-report measures (administered 
at the starred time points in Figure 3), as well as receiving their assigned training condition. 
V2 will occur on the following day at the same time as V1. 
▪ 
Procedures for Audio/Visual Recording:  
The diagnostic interview during the remote session will be recorded via HIPAA compliant 
platform (e.g., Zoom, Teams) to be used for supervision purposes as well as to ensure 
diagnostic fidelity.  
▪ 
Study Instruments:  
Puff topography will be objectively measured with the CReSS micro (Plowshare Technologies, 
Borgwaldt KC, Inc), a hand-held device that has a sterilized flow meter mouthpiece that is 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
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connected to a pressure transducer, which converts pressure into a digital signal that is sampled 
at 1,000Hz. Puff indices will be averaged and examined at puff-to-puff level. To index changes 
in CVC as a function of condition, continuous ECG and respiration data will be sampled at 
1,000Hz, and differences in RSA from the 5-min adaptation period (V1) to the 5-min peri-
smoking period (V2) will be derived and scored using cardiopro in accord with established 
guidelines.73 Smoking reinforcement will be assessed with: (a) the Short-Cigarette Purchase 
Task (S-CPT),74 a hypothetical purchase task designed for repeated assessment of cigarette 
(wanting), modified to purchasing of the “last cigarette smoked” to index intensity (consumption 
when free), Omax (maximum expenditure on cigarettes), and breakpoint (point at which 
consumption is zero) and (b) the Modified Cigarette Evaluation Questionnaire (mCEQ),75 which 
assesses how respondents feel about the “last cigarette smoked” with subscales that tap liking 
(cigarette satisfaction), wanting (craving reduction), and learning (psychological reward). 
 
▪ 
Subject Identifiers:  
Data will be de-identified with an arbitrary ID number. Subject identifiers of name, email 
address, address, and phone number will be stored under lock and key and in password-
protected electronic databases, separate from all data. 
 
B. Secondary Data Collection  
Additional measures administered and administration time points are included below in Table 1. Please 
refer to Figure 3 for where these time points fall in the visit procedures. Full measures are attached for 
review.  
Measure 
Screening 
Baseline  
(remote 
session) 
0 
Adaptation 
1 
1a, 
and 
1b 
Smoking 
2 
Rest 
Phone Screen. 
X 
 
 
 
 
 
 
 
Depression, Anxiety, 
and Stress Scales, 
21 Item Version 
(DASS-21).  
 
X 
 
 
 
 
 
 
The Mini 
International 
Neuropsychiatric 
Interview 7.0.0 
(MINI) sections C, I, 
J, and K. 
 
X 
 
 
 
 
 
 
Demographic 
information. 
 
X 
 
 
 
 
 
 
Smoking History 
Questionnaire. 
 
X 
 
 
 
 
 
 
Medical History 
Form. 
 
X 
 
 
 
 
 
 
McCarthur Ladder 
for Subjective Social 
Status. 
 
X 
 
 
 
 
 
 
Economic Strain 
Questionnaire. 
 
X 
 
 
 
 
 
 
Fagerstrom Test for 
Cigarette 
Dependence. 
 
X 
 
 
 
 
 
 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
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Mood and Anxiety 
Symptoms 
Questionnaire. 
 
X 
 
 
 
 
 
 
Multidimensional 
Experiential 
Avoidance 
Questionnaire. 
 
X 
 
 
 
 
 
 
Anxiety Sensitivity 
Index. 
 
X 
 
 
 
 
 
 
Distress Tolerance 
Scale. 
 
X 
 
 
 
 
 
 
Distress Intolerance 
Index. 
 
X 
 
 
 
 
 
 
Brief WISDM. 
 
X 
 
 
 
 
 
 
Positive And 
Negative Affect 
Schedules (PANAS). 
 
X 
 
 
 
 
 
 
Pittsburgh Sleep 
Quality Index. 
 
X 
 
 
 
 
 
 
Readiness to Quit. 
 
X 
 
 
 
 
 
 
Difficulties in 
Emotion Regulation 
Scale. 
 
X 
 
 
 
 
 
 
Avoidance and 
Inflexibility Scale. 
 
X 
 
 
 
 
 
 
Pre-Session Review 
Sheet 
 
 
X 
 
 
 
 
 
Modified Cigarette 
Evaluation 
Questionnaire. 
 
 
 
 
 
 
 
X 
Hypothetical 
Cigarette Purchase 
Task. 
 
X 
 
X 
 
 
 
X 
Visual Analogue 
Scales of Discrete 
Affective States. 
 
 
X 
 
X 
 
X 
 
Brief Questionnaire 
of Smoking Urges.  
 
 
X 
 
X 
 
X 
 
State Difficulties in 
Emotion Regulation 
Scale – modulation 
subscale.  
 
 
 
 
X 
(not 
1a) 
 
 
 
Expired CO. 
 
 
X 
 
 
 
X  
 
CReSS topography. 
 
 
 
 
 
X 
 
 
Psychophysiological 
parameters (e.g., 
RSA, BVP, 
Respiration). 
 
 
 
X 
 
X 
 
X 
 
 
 

 
 
 
 
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Reinforcement 
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2.0 Project Management 
 
2.1 Research Staff and Qualifications 
 
Key Personnel:   
 
Principal Investigators.  
Samantha Farris, Ph.D. Dr. Farris is an Assistant Professor in the Department of Psychology at 
Rutgers University, a licensed clinical psychologist in the Department of Psychology. Dr. Farris has 
expertise in naturalistic and experimental methods to study smoking reinforcement, including 
overseeing observational protocols for puff topography with use of technology-aided handheld devices. 
Dr. Farris also has expertise in the management and processing of puff topography data. Dr. Farris will 
devote 100% of 1 month’s effort (i.e., 13 hours/week, for 12 weeks) to the project to ensure that the 
project is completed within the one-year period. Specifically, she will be responsible for: a) overall 
management of the project and IRB; b) training and supervision of puff topography via CReSS micro; 
c) oversight of assessment of reinforcer pathology; d) oversight of safety, data monitoring, and data 
processing related to puff topography; and e) statistical analyses. 
 
 Teresa Leyro, Ph.D. Dr. Leyro is an Assistant Professor in the Department of Psychology at Rutgers 
University and a licensed clinical psychologist. Dr. Leyro has expertise in psychophysiological 
assessment (e.g., heart rate, respiration) and use of biofeedback paradigms in the context of substance 
use, in addition to expertise in conducting experimental laboratory-based studies in emotion and 
smoking. Dr. Leyro will also devote 100% of 1 month’s effort (i.e., 13 hours/week, for 12 weeks) to this 
project to ensure that the project is completed within the one-year period. Specifically, she will be 
responsible for: a) management of study recruitment and retention; b) oversight of assessment of 
respiratory parameters; c) training and supervision of biofeedback paradigm; and d) oversight of safety, 
data monitoring, and data processing related to biofeedback paradigm. 
 
Project Coordinators. Danielle Hoyt, M.A. Ms. Hoyt is a graduate student in the Department of 
Psychology at Rutgers University under the mentorship of PI Leyro. Ms. Hoyt will also attend/participate 
in weekly study meetings with the MPIs to discuss study progress and problem-solve issues as they 
arise. Hannah Brinkman, B.A. is also a graduate student in the Department of Psychology at Rutgers 
University under the mentorship of PI Leyro. They will be largely responsible for technical aspects of 
the study including recruitment, telephone screening, scheduling and appointment reminders, retention, 
conducting baseline assessments and experimental protocol, maintaining study records/IRB, and 
overseeing research assistants. 
 
Other Personnel:  
 
Post-Doctoral Researcher. Brianna Altman is a post-doctoral researcher in the Clinical Psychology 
Rutgers REHAB and ABUSA lab under the supervision of Drs. Leyro and Farris. She completed 
extensive training in evidence-based smoking cessation treatment and will serve as an independent 
assessor.  
 
Graduate Student Researchers. Jacqueline Smith, M.A, Mindy Kibbey, B.A., Lilly Derby, B.S., 
Lauren Davis, B.S., Allison Bond, M.A., and Sonali Singal, B.A. are graduate students in the Clinical 
Psychology program at Rutgers University, under the supervision of Drs. Leyro and Farris. They have 
each completed extensive training in evidence-based smoking cessation treatment and will serve as 
independent assessors. 
 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
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Research Assistants. Sayaka Carpenter, Dana Steinberg, Isabel Cunha, Gabriela Rivera, and 
Brittany Keller are post-baccalaureate laboratory managers and project coordinators for Drs. 
Farris and Leyro and Kathleen Kildosher, Dipabali Jana, Aisha Ghauri, Huong (Valerie) Le, Jason 
Marum, Lori Khadse, Samantha Stucchi, Annmarie Elgendy, Gabriel Brevet, Helena Beshay, 
Marcus Shipp, Nidhi Gourabathuni, Rutu Patel, Patricia DiFalco, Priyanka Taribagil, Jorge 
Rivera, and Long Tran are research assistants under the supervision of Drs. Farris and Leyro. They 
will assist with subject recruitment, participant visits, data entry and coding, and compiling study 
materials. 
 
2.2 Research Staff Training 
All research personnel will receive, if they have not already, extensive (10-15 hours) training on all study 
procedures. PIs Dr. Farris and Dr. Leyro will oversee training, which will include verbal description and 
behavioral demonstration. Staff will then be led through the study’s procedures as mock participants, 
before administering each study task to the PIs or graduate students designated by the PIs to allow for 
sufficient practice and corrective feedback if necessary. All study staff have previously administered some 
or all of the aforementioned techniques during prior investigations. 
 
2.3 Resources Available 
Research will take place in the Affective and Biological Underpinnings of Substance Use and Anxiety 
(ABUSA) laboratory in the Department of Psychology on the second floor of One Spring Street, New 
Brunswick. These facilities include the materials necessary for data collection (e.g., carbon monoxide 
smokerlyzer, physiological monitoring) and secure storage (e.g., locked file cabinets, password-secure 
computers). 
 
2.4 Research Sites 
The Affective and Biological Underpinnings of Substance Use and Anxiety (ABUSA) laboratory in the 
Department of Psychology on the second floor of One Spring Street, New Brunswick. 
 
3.0 Multi-Center Research 
N/A. 
 
4.0 Subject Considerations 
 
4.1 Subject Selection and Enrollment Considerations  
 
A. Method to Identify Potential Subjects 
Participants will be recruited through: (a) free online internet advertisement (e.g., Facebook posts, 
Craigslist), (b) flyers posted in the community and health-related clinics in the New Brunswick and Central 
New Jersey area, and (c) paid advertisements through BUMP Digital Marketing and Build Clinical, both 
online recruitment services used in previous research by both PIs. BUMP and Build Clinical will target 
daily smokers in the Northern and Central New Jersey areas via targeted advertisements on Facebook, 
Instagram and other social media sites and websites. Recruitment materials are attached. Any individuals 
meeting inclusion/exclusion criteria will be provided the opportunity to participate in this study. Individuals 
interested in participation will undergo a brief phone screen to determine presence of inclusion criteria 
and absence of exclusion criteria. 
B. Recruitment Details 
We intend to recruit 180 daily smokers and retain 80 eligible. The study will be conducted at the 
Affective and Biological Underpinnings of Substance Use and Anxiety (ABUSA) laboratory at Rutgers 
University, in New Brunswick, NJ. The ABUSA laboratory (directed by MPI Leyro) has a 
psychophysiological suite and ventilated in-laboratory smoking room. Through our studies 
(R03DA041556; F31DA024919; R21DA045182; R34DA043751), we have developed effective 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
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strategies to recruit emotionally-distressed smokers from the community at a consistent rate. We will 
recruit via community fliers and announcements, local tobacco clinics (via Co-Is Steinberg/Delnevo), 
and both BUMP digital marketing and Build Clinical, online recruitment services.  
 
Subject Screening 
Potential participants will be screened via telephone by protocol-approved research staff, trained 
under the direction of Drs. Leyro and Farris. See section 11.0 Recruitment Materials for the full text of 
the phone screen.  
▪ 
Inclusion Criteria 
▪ 
(1) Age 18-55; (2) daily smoking ≥ 8 cigarettes/day verified by carbon monoxide analysis of 
breath sample ≥ 5 ppm;64 (3) smoking within 30 min of waking; and (4) English fluency.  
▪ 
Exclusion Criteria  
(1) current smoking cessation treatment; (2) past-month reduction of cigarettes/day by ≥50%; 
(3) non-nicotine substance use disorder (moderate or severe); (4) past-year psychiatric 
instability (e.g., psychosis, mania); (5) severe visual, hearing, or cognitive impairments; (6) 
medical condition that could impact stress reactivity or physiology (e.g., respiratory, 
cardiovascular, autoimmune, pregnancy, neurodegenerative disorders); and (7) current 
regular use of medication that could affect CVC (e.g., beta blockers, benzodiazepines; note-
use of SSRIs/SNRIs is permitted if dose is stable ≥ 6 wks).  
 
 
4.2 Secondary Subjects 
N/A. 
 
4.3 Number of Subjects 
 
A. Total Number of Subjects 
80 total participants are expected to complete the full protocol. In order to have 80 full completers 
(attendees that remain eligible and complete both visits), 180 are expected to be initially enrolled. 
 
B. Total Number of Subjects If Multicenter Study 
N/A. 
 
C. Feasibility 
Based on our prior trials, we expect to retain 90% of subjects across the two visits. Financial 
incentives will also aid in retention: with $20 for completing the remote screening/baseline visit, $30 
for completing V1 and $100 for completing V2. We have used this back-loaded schedule of 
compensation in our prior smoking lab-studies with high retention rates (F31DA024919; 
F31DA035564). Additionally, with the use of Build Clinical and BUMP Digital Marketing, we expect to 
be able to consent and enroll 80 completers very feasibly. Prior engagement through both labs with 
BUMP’s recruitment service has yielded up to 12 inquiries per day in prior smoking research, and the 
eligibility criteria would allow a broad scope of potential participants. 
 
4.4 Consent Procedures 
 
A. Consent Process 
▪ 
Location of Consent Process 
The initial consent process will take place via video conferencing software during the initial 
remote visit. Consent to the TSST procedures will occur in the laboratory at One Spring 
Street at the start of V2.  
▪ 
Ongoing Consent 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
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Ongoing consent will be confirmed on the basis of ongoing communication and study 
participation. In addition, participants will explicitly be reminded of study expectations, 
limitations, compensation, and right to withdraw. Study staff will attempt to contact 
participants who miss study appointments or follow-up appointments until they provide verbal 
or written indication that they no longer wish to participate.  
▪ 
Individual Roles for Researchers Involved in Consent 
All of the research assistants, graduate students, and project manager have been trained and 
are experienced in prior consent administration and may collect consent from participants 
through the course of the protocol. 
▪ 
Consent Discussion Duration 
Staff will go over details regarding the procedure, time commitment, payment, risks/benefits, 
and option to discontinue the study at any time without penalty. We anticipate that it will take 
participants 5 minutes to read the consent and up to an additional 5 for staff to review 
relevant information.   
▪ 
Coercion or Undue Influence 
During the consent process, staff will make clear to participants that they will receive full 
compensation if eligible, and that early termination will result in payment for the portion 
completed, as detailed in the consent, and will not result in loss of ability to participate in 
future research. 
Subject Understanding 
Participants will be asked if they require any clarification and must verbally indicate they fully 
understand all study procedures, in addition to providing written consent. 
 
B. Waiver or Alteration of Consent Process  
N/A. 
 
C. Documentation of Consent 
▪ 
Documenting Consent 
All participants will sign the consent form, indicating their consent.  
▪ 
Waiver of Documentation Of Consent (i.e., will not obtain subject’s signature) 
N/A. 
 
4.5 Special Consent/Populations 
N/A. 
 
4.6 Economic Burden and/or Compensation for Subjects 
 
A. Expenses  
Participants may incur costs of transportation to arrive at the study site. Travel and transportation 
costs will not be reimbursed.  
B. Compensation/Incentives 
Participants will receive compensation in cash. Participants will receive compensation based on 
study attendance and continued eligibility. They will receive $30 for the remote 
screening/baseline session. If eligible to continue, they will receive an additional $70 upon 
completion of V1. If they return for V2, participants will receive $100 for participating in V2 and 
a $50 completion bonus. Compensation totals a potential of up to $250 per participant. 
C.  Compensation Documentation 
Participants will sign receipts indicating their receipt of compensation. Compensation will also be 
logged electronically in a tracking log accessible only to research staff.  
  
4.7 Risks of Harm/Potential for Benefits to Subjects 
 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
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Reinforcement 
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A. Description of Risks of Harm to Subjects 
(1) Phone Screen and Questionnaire Completion: Potential participants may become 
uncomfortable or distressed when asked certain questions (e.g., regarding illicit 
substance use; current/past mental health and physical health). However, Drs. Leyro and 
Farris have many years of experience administering these questionnaires in various 
study protocols and study personnel will receive extensive training in conducting the 
Phone Screen. Also, participants will be offered an additional layer of protection via a 
Certificate of Confidentiality. 
(2) PTBT: There are some minimal risks associated with the administration of the 
proposed breathing interventions.  The most often observed risk is discomfort breathing 
at a pace that is much slower than typical and worry that one is not inhaling adequate air. 
To address this potential risk, study clinicians will be carefully trained in providing 
participants with a clear rationale for the procedure, clinical management of distress 
associated with the intervention, and appropriate adjustments to ensure participants are 
able to adhere to the protocol.  
(3) Physiological Recording: All of our sensors record responses from the surface of the 
body and are hence noninvasive and should not cause the participants any discomfort or 
physical harm. Patients may experience mild discomfort with the application and removal 
of passive electrodes to monitor their physiological parameters. However, we do not 
anticipate this discomfort to be longstanding. To minimize discomfort, all sensors are 
placed and removed by study staff that will receive training in appropriate placement and 
removal. 
 (4) Assessment Procedures: No risks are associated with self-report or behavioral 
assessments other than mild distress due to the sensitive nature of questions or induced 
distress as a function of difficulty or attention demands on some of the behavioral tasks. 
Study personnel are experienced and sensitive to this issue and will cease testing if a 
participant displays excessive frustration during behavioral testing, although neither PI 
has experienced this in her prior research.   
 
B. Procedures which Risk Harm to Embryo, Fetus, and/or Pregnant Subjects 
N/A. 
C. Risks of Harm to Non-Subjects 
N/A. 
D. Assessment of Social Behavior Considerations 
No risks are associated with self-report or behavioral assessments other than mild distress due to 
the sensitive nature of questions or induced distress as a function of difficulty or attention 
demands on some of the behavioral tasks. Study personnel are experienced and sensitive to this 
issue and will cease testing if a participant displays excessive frustration during behavioral 
testing, although the PI has never experienced this in her prior research.   
E. Minimizing Risks of Harm 
Described above in section A and D. 
▪ 
Certificate of Confidentiality 
This research is covered by a Certificate of Confidentiality. Researchers with this Certificate 
may not disclose or use information or documents that may identify study participants in any 
federal, state, or local civil, criminal, administrative, legislative, or other action, suit, or 
proceeding, or be used as evidence, for example, if there is a court subpoena, unless study 
participants have consented for this use. Information or documents protected by this 
Certificate cannot be disclosed to anyone else who is not connected with the research 
except, if there is a federal, state, or local law that requires disclosure (such as to report child 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
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abuse or communicable diseases but not for federal, state, or local civil, criminal, 
administrative, legislative, or other proceedings, see below); if participants have consented to 
the disclosure, including for their medical treatment; or if it is used for other scientific 
research, as allowed by federal regulations protecting research subjects.  A Certificate of 
Confidentiality does not prevent participants from voluntarily releasing information about 
themselves or their involvement in this research. If a participant wants their research 
information released to an insurer, medical care provider, or any other person not connected 
with the research, they must provide consent to allow the researchers to release it. The 
Certificate of Confidentiality will not be used to prevent disclosure as required by federal, 
state, or local law of harm to self or others as well as reports of child and elderly abuse and 
neglect. 
▪ 
Provisions to Protect the Privacy Interests of Subjects 
Our research team employs standard procedures to ensure confidential information about study 
participation is not disclosed. All data are linked to an arbitrary study ID unrelated to personal 
information. The file linking participants to their study ID will be stored in a password-protected 
file, located within a password-protected database on an encrypted computer and maintained 
separately from de-identified personal data files. Only select trained laboratory personnel will have 
access to the file. All computer files or printed data used for analysis also will be de-identified. 
Consent forms and payment forms will be stored in a locked file cabinet separate from data in an 
office that is locked when not occupied. Participants’ confidentiality also is protected by never 
associating a participant’s name with results in any published or otherwise publicly presented 
report. Demographic information, including information about participants’ age, ethnicity, 
education, marital status and employment status, will be reported using averages and percentages 
computed over multiple participants and never reported at the level of individual participants.  
F. Potential Benefits to Subjects 
While no individual benefits for subjects are anticipated, the data obtained through this study may 
help inform and shape effective interventions for smoking cessation. 
 
5.1 Health Insurance Portability and Accountability Act (HIPAA) 
N/A. 
5.2 Family Educational Rights and Privacy Act (FERPA) 
N/A. 
5.3 Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations) 
 
A. Special Populations 
N/A. 
 
5.4 General Data Protection Regulation (GDPR) 
N/A. 
 
5.5 NJ Access to Medical Research Act (Surrogate Consent) 
N/A. 
 
6.0 Data Management Plan 
 
6.1 Data Analysis 

 
 
 
 
PI: Teresa Leyro, Ph.D.; Samantha Farris, Ph.D. 
Protocol Title: Puff Topography Biofeedback on Smoking 
Reinforcement 
Protocol Version Date: 2020000645 v.21  05/02/2023 
 
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Prior to conducting outcome analyses, we will use descriptive statistics and graphical analysis to evaluate 
the distributional properties of outcome variables. T-tests and χ2 initial analysis will be used to evaluate 
the equivalence of the groups on baseline variables (i.e., successful randomization).  
 
Test of Aim 1: First, tests of the effects of puff training on puff topography indices (i.e., puff volumes and 
duration, and inter-puff intervals) will be conducted using linear regression models. The mean level of 
each index over the course of the stress-precipitated smoking session will be calculated for each 
individual to be used as outcomes. The primary independent variable is training group (PTBT vs. Control. 
Planned covariates include biological sex (0=male, 1=female), number of cigarettes per day, and 
emotional distress (DASS-21), and the models will be tested with and without covariates. Effect size (d) 
will also be calculated. In addition, a series of multilevel models will be used to test whether 1) the mean 
levels and 2) changes in the levels of puff topography (i.e., volume, duration, inter-puff intervals) during 
stress-precipitated smoking session differ across groups. Levels of puff volumes, durations, and inter-puff 
intervals for each puff (outcomes), and puff number (level 1) make up the first level of data nested within 
individuals at the second level. Training group and other baseline characteristics will be entered in the 
models as level 2 variables.  We will examine the effects of PTBT (vs. Control) on the individual mean 
(i.e., the middle point of the values over time) and the individual trajectory slope (i.e., the rates of changes 
over time) for each topography index in separate models. A cross-level interaction term between training 
group (level 2) and puff number (level 1) will be included in each model. Puff number will be centered 
around the mid-point for each individual so that the intercept reflects the estimated mean level of each 
topography outcome. Separate quadratic and cubic slopes (squared and cubic puff number) will be 
included as level 1 predictors if their inclusion improves model fit. Intercepts and slopes will be specified 
as random if it improves model fit and coefficients varied significantly across individuals. Deviance 
statistics will be used to compare model fit between two models.79 Unconditional models will be initially 
estimated, and then training group will be included as a level-2 variable predicting level-1 intercept and 
slope coefficients. The models will be fitted with and without level 2 planned covariates (i.e., sex, FTCD, 
DASS-21, and the baseline average value of the corresponding outcome).  
 
Test of Aim 2: The effects of PTBT vs. Control on acute smoking reinforcement (i.e., cigarette purchase 
task [S-CPT], cigarette satisfaction/reward [mCEQ]) following stress-precipitated smoking will be 
estimated using separate linear regression models with group predicting each outcome. Planned 
covariates include the baseline value of the outcome when relevant (S-CPT), biological sex, number of 
cigarettes per day, and DASS-21, and the models will be tested with and without covariates. Effect size 
(d) will also be calculated.  
 
Test of Aim 3 (Exploratory Analyses): Differences in CVC (via RSA) between training groups during the 
stress-precipitated smoking trial will be tested using linear regression models, controlling for baseline 
levels. Training group will be used to predicting CVC (outcome). Covariates will be identical to those in 
prior analyses, and will be tested with and without covariates, and effect size (d) will be calculated.  
 
6.2 Data Security 
A master list of names and numbers is kept in a separate location and is used to facilitate the collection of 
data. Specifically, this Master list will be stored in a password protected excel document stored on 
Microsoft Teams, which is a secure cloud-based file storage application. Only senior staff will have 
access to the master list linking names and code numbers. Clinically important assessment data (e.g., 
suicidal intent) will be made available to clinical staff to more effectively coordinate services. All research 
staff directly involved with study participants will be fully trained by the PIs and will demonstrate 
competence in procedures for clinical assessment and appropriate intervention to address psychiatric 
adverse events. In such cases, research staff will also immediately contact a PI (Dr. Farris or Dr. Leyro) 
who will be on call at all times. Appropriate clinical action will be taken in such circumstances. Individuals 
will be provided with a list of referrals for counseling as needed. 
 

 
 
 
 
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All staff will be fully trained in relevant ethical principles and procedures, particularly around 
confidentiality. All assessment and treatment procedures will be closely supervised by Dr. Farris and Dr. 
Leyro. No personal participant information will be presented in any publication or presentations resulting 
from this research. 
 
6.3 Data and Safety Monitoring 
 
 
A. Data/Safety Monitoring Plan 
We believe that potential risks to participants in this study will be minimal. The risks do include the possibility 
of psychological distress during study screening. All research staff directly involved with study participants 
will be fully trained by the PIs and will demonstrate competence in procedures for clinical assessment and 
appropriate intervention to address psychiatric adverse events. In such cases, research staff will also 
immediately contact a PI (Dr. Farris or Dr. Leyro) who will be on call at all times. Appropriate clinical action 
will be taken in such circumstances. Individuals will be provided with a list of referrals for counseling as 
needed. 
 
The principal investigators, Drs. Farris and Leyro, will take ultimate responsibility for safety monitoring in 
the study. They will be in frequent contact with the study Co-Is and study staff. All adverse events will be 
promptly reported to the PI. Any incident involving a serious injury, medical hospitalization, or death will be 
reported to the Rutgers IRB as a Serious Adverse Event (SAE) within 24 hours. SAEs will be reviewed by 
the full committee of the Rutgers IRB. The report will include whether they were expected or unexpected, 
a rating of severity of the event, a brief narrative summary of the event, a determination of whether a causal 
relationship existed between the study procedures and the event, whether the informed consent should be 
changed as a result of the event and whether all enrolled participants should be notified of the event. 
Serious and other unexpected adverse events will also be tracked and reported semi-annually to the IRB.  
  
In terms of data monitoring, self-report measures will be entered by participants directly into Qualtrics (a 
data entry and management program). Data is stored on a secure cloud-based server that will only be 
accessible to the PI and relevant research team members. Physiological data will be stored electronically 
in files accessible only to research staff. Data will be reviewed post-collection by the PIs or a graduate 
researcher for validity and quality of collection. 
 
 
B. Data/Safety Monitoring Board Details 
N/A. 
 
6.4 Reporting Results 
 
A. Individual Subjects’ Results  
Individual results will not be shared with subjects. 
B. Aggregate Results 
Aggregate results will not be shared with subjects. 
C. Professional Reporting 
Results from this study, negative or positive, will be shared with the greater scientific community 
via manuscripts published in peer-reviewed journals, as well as through posters and presentations 
at relevant scientific conferences. No individual or identifying data will be presented. 
 
Clinical Trials Registration, Results Reporting and Consent Posting 
N/A. 
 
6.5 Secondary Use of the Data    

 
 
 
 
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After data have been collected and study results published, de-identified data will be made available to 
other qualified researchers upon request, on a CD or other electronic means compatible with our 
systems. The request will be evaluated by the PIs to ensure that it meets reasonable standards of 
scientific integrity. We have carefully selected standardized and widely-used assessments of affective 
states, emotional vulnerability, and smoking order to promote data sharing and integration into larger 
databases and to allow other researchers to analyze the data, including conducting meta-analyses. We 
may also choose to share de-identified data with colleagues/collaborators at other institutions. We will 
work on the data dictionary throughout the study. We will submit primary results for publication by the end 
of the project period, and will have final de-identified datasets and data dictionaries available by the end 
of the project period.   
 
7.0 Research Repositories – Specimens and/or Data 
 
N/A. 
 
8.0 Approvals/Authorizations 
 
N/A. 
 
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Reinforcement 
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Reinforcement 
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