Clinical trial NCT05224050
Conditions: Tobacco Smoking
Keywords: Smoking Cessation Heart Rate Variability Biofeedback
Sponsor: Rutgers, The State University of New Jersey
Start date: 2021-11-29; Completion date: 2023-06-15
Enrollment: 28 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of the study is to conduct an open trial examining the feasibility and acceptability of an adapted heart rate variability biofeedback and smoking cessation treatment that was using a primarily virtual remote intervention.

Detailed description:
The present investigation is an open trial investigating the feasibility and acceptability of heart rate variability biofeedback smoking cessation treatment (HRVB-SCT) for individuals who smoke cigarettes. Significant findings will also support the expansion of HRVB as a transdiagnostic treatment adjunct that alters cardiac vagal functioning to promote emotional and behavioral regulation, changing the status quo of cognitive-behavioral intervention approaches and decreasing the health and economic burden of smokers who suffer from emotional distress.

The goals are to: (a) assess the feasibility and acceptability of the HRVB-SCT intervention (b) assess the efficacy of the intervention in modifying smoking behavior and emotional distress; and (c) collect additional information to inform a subsequent randomized clinical trial.

Arms: arm 1: All participants in this open trial will receive individualized training in resonance breathing using biofeedback to help improve self-regulation (HRVB), cognitive-behavioral smoking cessation treatment (SCT), and up to 8-weeks of the transdermal nicotine patch (NRT).
Interventions: intervention 1: Cognitive-Behavioral Smoking Cessation intervention 2: Heart Rate Variability Biofeedback intervention 3: Nicotine patch
Intervention descriptions: intervention 1: Participants will be provided with six individualized smoking cessation counseling sessions designed to help them prepare to quit, set a quit date, behaviorally manage early abstinence, and to resume cessation upon lapse. intervention 2: Participants will be provided with seven individualized trainings in resonance breathing using biofeedback to help improve self-regulation. intervention 3: All participants will be offered up to eight weeks of transdermal nicotine patch, beginning on their quit date.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
 
 
 
TITLE: Open Trial of Heart Rate Variability Biofeedback for Smoking Cessation 
NCT05224050 
PI: Teresa Leyro, Ph.D. 
Document Date: 09/28/2022 
 


Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v9 9/23/22
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1.1
INTERVENTIONAL
RESEARCH PROTOCOL TEMPLATE
(HRP-503a)
STUDY INFORMATION

Title of Project:
Open Trial of Heart Rate Variability Biofeedback for Smoking Cessation

Principal Investigator Name
Name: Teresa M. Leyro, Ph.D.

Principal Investigator Div. & Dept.
Division & Department: Psychology

Principal Investigator Contact Info:
Room 539, Tillett Hall, 53 Avenue E., Piscataway, NJ 08854 Telephone
Number: 848-445-2090
Email: teresa.leyro@rutgers.edu

Protocol Version and Date:
V9, 9.23.2022
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Protocol Title: Open Trial of HRVB-SCT
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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)
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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
1.0 Research Design
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1.1 Purpose/Specific Aims
The purpose of the study is to conduct an open trial assessing the feasibility and acceptability of a refined 
heart rate variability biofeedback as a smoking cessation treatment adjunct for individuals who smoke 
cigarettes.
A.  Objectives 
The present investigation is an open pilot trial  assessing the acceptability and feasibility of a heart rate 
variability (HRV) biofeedback smoking cessation treatment (HRVB-SCT) for individuals who smoke 
cigarettes. Primary significant findings will support the integration of HRVB as an acceptable and feasible 
treatment adjunct to standard smoking cessation treatment. Secondary significant findings will support the 
expansion of HRVB as a transdiagnostic treatment adjunct that alters cardiac vagal functioning to 
promote smoking cessation outcomes and emotional and behavioral regulation. Together, primary and 
secondary findings will support changes to the status quo of cognitive-behavioral intervention approaches 
and decrease the health and economic burden of smokers who suffer from emotional distress.
The goals are to: (a) assess the acceptability and feasibility of the HRVB intervention as an treatment 
adjunct to SCT (b) assess changes in smoking behavior and emotional distress and (c) collect additional 
information to assist in further refining the intervention for a larger R01 RCT. 
B.  Hypotheses / Research Question(s)
1.
Primary Analysis: To complete a pilot open trial analyzing the feasibility and acceptability of HRVB-
SCT. Intervention feasibility and acceptability will be indexed by measures of i participant attendance 
and practice adherence, participant self-report ratings of intervention satisfaction, effectiveness, 
appropriateness, and ease, and therapist reported technological limitations. 
2.
Secondary Analysis: To examine whether smokers receiving HRVB-SCT evidence improvements in: 
(1) smoking behavior as indexed by self-reported quit-day abstinence, verified by carbon monoxide 
breath analysis (CO<8ppm); sustained smoking cessation, verified by CO and salivary cotinine 
levels (<10ng/mg); and self-reported reductions in smoking rate and (2) emotional distress as 
indexed by self-reported anxiety, mood, and stress ratings. We expect HRVB-SCT will be associated 
with significant improvements in smoking and emotional health outcomes. 
1.2 Research Significance
Cigarette smokers are disproportionately affected by mood and anxiety disorders (Lawrence, Mitrou & 
Zubrick, 2009), which impede cessation (Piper, Cook, Schlam, Jorenby & Baker, 2011; Zawertailo & 
Selby, 2015; Williams, Steinberg, Griffiths & Cooperman, 2013). This Stage II study will further test the 
feasibility, acceptability, and efficacy of an integrated, biobehavioral, transdiagnostic smoking intervention 
for individuals who smoke cigarettes. The neurovisceral integration model (Thayer & Lane, 2000; Park & 
Thayer, 2014) suggests that cardiac vagal functioning plays a critical role in the effective modulation of 
physiological, emotional, and cognitive processes necessary for self-regulation. Dysregulation in this 
system is observed across various forms of psychopathology (Moon, Lee, Kim & Hwang, 2013) and 
cigarette smoking (Thayer & Lane, 2000; Park & Thayer, 2014; Thayer, Åhs, Fredrikson, Sollers & Wager, 
2012; Park, Van Bavel, Vasey & Thayer, 2013). Moreover, cardiac vagal activity is associated with 
emotional disorder severity and recovery (Jain, Cook, Leuchter, et al, 2014; Rottenberg, Salomon, Gross 
& Gotlib, 2005) as well as smoking onset and maintenance (Ashare, Sinha, Lampert, et al, 2012; Libby, 
Worhunsky, Pilver & Brewer, 2012; Crane, Gorka, Giedgowd, et al., 2016). HRVB interventions offer a 
simple and effective means of promoting self-regulation via restoration of the vagal system (Lehrer, 
Vaschillo E, Vaschillo B, et al., 2003; Lehrer, Vaschillo E, Vaschillo B., 2000; Lehrer & Vaschillo, E, 2004) 
but have not been applied to smokers with moderate emotional distress. Via the application of HRVB, the 
current proposal will target the vagal system to improve adaptive and flexible self-regulation (Kashdan & 
Rottenberg, 2010), thereby supporting smoking cessation and emotional health. Thus, a primary aim of 
this proposal is to develop and pilot test HRVB as a feasible, acceptable, and effective treatment adjunct 
for standard smoking cessation treatment (HRVB-SCT) in daily smokers.
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Based on a strong body of empirical work demonstrating the benefits of HRVB in reducing anxiety 
(Henriques, Keffer, Abrahamson, & Horst 2011) and depressive symptoms (Patron et al., 2013; Rene, 
2008) a secondary aim of this proposal is to evaluate the efficacy of HRVB-SCT in improving smoking 
and emotional health outcomes among adults who smoke. Transdiagnostic processes that promote 
avoidance and escape of emotional distress are implicated in the development and maintenance of 
cigarette smoking dependence (Baker, Piper, McCarthy, Majeskie & Fiore, 2004), and may also explain 
why individuals with depressive and anxiety symptoms are more susceptible to cigarette smoking 
dependence and poor cessation outcomes (Leventhal & Zvolensky, 2015). Existing smoking cessation 
interventions informed by these models largely rely upon cognitive-behavioral strategies (Gifford, 
Kohlenberg, Hayes, et al., 2011; Brown, Reed, Bloom, et al., 2013.) However, automatic visceral 
responses to emotional distress may impede the utilization of intentional self-control strategies. 
Biobehavioral interventions that directly address transdiagnostic physiological processes may offer a 
more targeted means of improving outcomes, thereby identifying an alternative treatment mechanism. 
Moreover, the development of biobehavioral interventions may improve smoking cessation outcomes for 
smokers with moderate emotional distress who are not responsive to, or are less receptive of, cognitive-
behavioral interventions. 
The proposal will use a staged model for developing and standardizing behavioral interventions, as 
indicated by NIDA. The first phase (i.e., Phase 1A) of the project has focused on drafting, piloting, and 
modifying an integrated HRVB smoking cessation treatment (HRVB-SCT). The second phase of the project 
(Phase 1B) will focus on assessing the acceptability and feasibility of treatment delivery, fidelity, and 
potential for improving smoking cessation outcomes and reducing emotional distress. Data collected during 
this time will also potentially inform a larger R01 application of a RCT of HRVB-SCT to evaluate smoking 
and emotional distress outcomes and explore transdiagnostic physiological and cognitive-affective 
treatment mechanisms.
1.3 Research Design and Methods
A.
Research Procedures
Overview: The current proposal represents the second phase of treatment development and will involve 
evaluating the acceptability and feasibility of HRVB-SCT treatment deliveryas well as examining whether 
participants receiving HRVB-SCT evidence improvement in smoking outcomes and emotional health. 
Individuals enrolled in this pilot clinical trial will include 30 adult daily cigarette smokers.. 
Recruitment Approach: Smokers interested in receiving free smoking cessation treatment will be 
recruited from the greater Rutgers, New Brunswick community via posters, leaflets, mailings, online 
advertisements, community outreach (i.e., meetings with local organizations and treatment providers who 
work with cigarette smokers), and listservs. We will determine eligibility via completion of a structured 
phone interview and in-person assessment. 
Pre-Study Telephone Screening: Upon interacting with study recruitment materials, prospective 
participants will be given the option to complete a virtual pre-phone screen via QR code, or to contact the 
lab in which the pre-phone screen will be conducted verbally. After the initial pre-screen, if prospective 
participants are deemed eligible for the next steps, they will complete a phone interview where they will 
be provided with an overview of the study and assessed for detailed inclusion/exclusion criteria (e.g., 
readiness to quit, current smoking status, and health exclusionary criteria. Participants who remain 
interested in the study and appear to meet initial study inclusion/exclusion criteria will be scheduled for a 
remote (i.e., Zoom) completion of the MINI-International Neuropsychiatric Interview (MINI) (Sheehan et 
al., 1998; see Table 2), a semi-structured clinical interview, to confirm inclusion/exclusion diagnostic 
criteria. If ineligible, the reason for exclusion will be tracked, and they will be referred to the Rutgers 
Tobacco Dependence Program, a free local clinic offering evidence-based pharmacological and individual 
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and group cessation treatments. Following confirmation of pre-screening eligibility criteria participants will 
be scheduled for their laboratory visit within one week and sent detailed instructions on behaviors to avoid 
that may confound physiological assessment (e.g., vigorous physical activity or consumption of caffeine 
within 2 hours, alcohol use within 12 hours). Lab sessions will be scheduled after 12 PM and at least four 
hours post-usual waking time. This will help control for high urges and withdrawal and low nicotine 
plasma levels associated with overnight deprivation.  
Baseline and Intervention Session 1 (approximately 190 minutes): In order to expedite their baseline 
appointment, prior to their visit, participants will be emailed the consent form to review ahead of time as 
well as well as meet with study personnel to review consent and fill out baseline surveys. Afterwards, if 
found eligible, subjects will be emailed and asked to complete a battery of self-report measures on 
Qualtrics, an online survey portal. Questionnaire data will be used to assess self-reported symptoms of 
depression, anxiety and stress, general health, a range of smoking relevant processes, other substance 
use, and self-reported and behaviorally indexed distress tolerance (see Table 2). If the participant has not 
completed the self-report battery via Qualtrics prior to the in-person visit, they will complete it via Qualtrics 
in the lab before proceeding with the rest of the baseline procedures.  At the start of the visit, participants 
will meet with an independent assessor who will verify smoking status via CO analysis of breath sample, 
re-confirm study inclusion/exclusion criteria and obtain written informed consent. Participants will next 
complete a physiological assessment during which electrocardiograph and impedance cardiography 
recordings will be collected. In addition to recording resting levels of participant physiology, participants 
will also be asked to complete a series of computerized cognitive tasks while physiological recordings are 
continuously assessed. An objective measure of the participant’s height (inches) weight (lbs) will also be 
collected using the lab’s medical grade scale. Because the baseline session also serves as the first 
respiratory and SCT intervention session, participants will be offered a 1-hour break and snack after 
completing all baseline assessments and continuing on to complete the remainder of study visit 
procedures. 
HRVB-SCT Intervention: After completing the baseline procedures, participants will be assigned to work 
with two trained study personnel for the SCT and HRVB intervention components, respectively.. 
HRVB Intervention: The initial in-person intervention session will last approximately 60 minutes. All 
remaining intervention sessions will last approximately 30-40 minutes (see Table 1). The HRVB 
intervention is designed to maximize respiratory sinus arrhythmia (RSA) by breathing at the resonance 
frequency of each individual’s baroreflex system, which varies around six breaths per minute. When 
breathing at this frequency, the effects of RSA and the baroreflex interact, producing large increases in 
low frequency (LF) power, reflecting an increase in both functions, as indexed via LF-HRV. Note that HF-
HRV during resonance frequency breathing no longer can be used as an index of vagal activity (i.e., 
RSA), because RSA is now represented in the LF range (Lehrer et al., 2003). Regular practice of 
resonance breathing appears to result in long-term improvements in vagus nerve activity that indeed can 
be indexed via HF-HRV (i.e., RSA) during baseline (i.e., non-biofeedback-period) breathing. Participants 
will complete 7 sessions of HRVB, two in-lab sessions and five remote sessions, over the course of 6 
weeks. Sessions are front-loaded with two sessions occurring during the first week (one in-lab session 
and one remote session) to ensure accurate training to promote quit day success (see Table 1). 
Clinicians will be trained in the application of HRVB including identifying and instructing participants to 
breathe at their resonance frequency using  the Inner Balance device by HeartMath software. The Inner 
Balance provides real time display of HRV and coherence recordings via a photoplethysmograph ear clip 
sensor that connects to the Inner Balance smartphone application via Bluetooth. This can be viewed by 
the participant via the Inner Balance smartphone app while simultaneously being shared with their 
respiratory therapist via Zoom. The combination of these features allow for respiratory therapists to 
provide participants with ongoing remote instruction including real time corrective feedback intended to 
maximize HRV. Inter-beat interval data is stored via HeartMath’s cloud storage and can be downloaded 
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by the research team remotely to assess intervention fidelity. HeartMath has a history of working with 
researchers conducting clinical trials of HRVB. The Inner Balance software was selected for this trial 
given its usability, portability, and cost-effectiveness. 
Homework Practice: Participants will be asked to practice HRV biofeedback 20 minutes daily, in bouts of 
5 minutes. Practicing for 20 minutes a day is necessary to most optimally train the reflexes that will help 
participants control stress response, cravings, and many other symptoms related to the autonomic 
nervous system (Lehrer, Vaschillo, & Zucker, 2013). In addition to verifying practice outside of 
intervention sessions, the Inner Balance device allows the investigators to download biofeedback data for 
quality assessment. Participants will also be prompted via Metricwire, a separate web-based platform 
developed for ecological momentary assessment [EMA], to provide ratings of cigarette craving and 
withdrawal, as well as relaxation and distress, on a 100-point scale both before and after completing daily 
respiratory training practice. This system is accessed using a free smartphone app, which allows the 
study team to acquire daily diary data from a participant’s smartphone and is secure, private, and HIPAA 
compliant. The Metricwire app will additionally be used to remind participants to practice on three 
occasions per day; this reminder will include information regarding their potential compensation for 
completing their respiratory training practice. Participants will have the option to immediately complete 
EMA prompts, and subsequently practice, or to complete ratings at a later time. Participants may also 
open the app on their own (i.e., self-initiated) to complete ratings at their own convenience. The goal of 
incorporating EMA data collection is to promote homework completion, increase adherence to and 
engagement with the assigned intervention, and provide quantitative data regarding the relation between 
breathing practice and craving, withdrawal, relaxation, and distress while minimizing data-entry error or 
recall bias. All participants will use Metricwire. If participants do not have a smartphone which supports 
the study apps, a smartphone will be loaned to them for the duration of their study participation.
Smoking Cessation Treatment (SCT): All participants will receive six smoking cessation counseling 
sessions lasting approximately 20-30m each. The first will also occur in-person, after the baseline portion 
of the initial in-person baseline assessment. In total, participants will complete two in-person SCT 
sessions (Sessions 1 and 7) and four remote teletherapy sessions via Zoom (Sessions 2-5; see Table 1). 
Trained research personnel providing SCT will use a protocol adapted from the National Cancer 
Institute’s Clear Pathways guide. Each participant will be provided with an adapted version of Clear 
Pathways and be given weekly assignments. Participants will receive an 8-week supply of transdermal 
Nicotine Replacement Therapy (NRT) patches, at their in-person baseline visit. Smoking cessation 
counselors will provide remote instruction and feedback on NRT use. Specifically, participants will be 
instructed to place their first nicotine patch upon waking on their quit day (Fiore et al., 2008). Participants 
who smoke ≥ 10 cigarettes daily will begin with a 2-week course of 21 mg patch, followed by 4-week taper 
of 2-weeks of the 14mg and 2-weeks of the 7mg patch. We will recommend that patients who smoke 5-9 
CPD begin with the 14 mg patch, as indicated by clinical practice guidelines. 
In-Lab Recording Sessions: In-lab physiological recordings will be conducted at baseline and in-person 
at weeks 6 (i.e., 1-month post-quit) and 15 (i.e., 3-months post-quit). to assess both within and between-
session changes in cardiac vagal parameters (i.e., vagal tone and flexibility). An objective measure of the 
participant’s height (inches) and weight (lbs) will also be collected using the lab’s medical grade scale. 
We will use Biopac to obtain five 5-minute recordings of continuous measures of electrocardiograph 
(ECG), respiration, blood pressure, and impedance cardiograph (IC). Following a 5-minute resting period, 
participants will complete the Plain Vanilla Task. This is a low cognitive task in which participants are 
asked to count the number of a particular color rectangle that appear on their screen. Following Plain 
Vanilla, participants will complete a 5-minute dot-tracking task. While viewing a computer screen, 
participants are oriented to several yellow circles that appear among many gray circles. The yellow circles 
then change to gray, and participants are asked to track them as they move around the screen. This 
cognitively demanding dot-tracking task has reliably been used in the past as an index of vagal flexibility 
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as indexed by pre- to post-changes in HF-HRV (Muhtadie, 2015). HF-HRV average during the 5-minute 
baseline will be used as our index of vagal tone.  
Remote Intervention Sessions: During sessions 1b, 2, 3, 4, and 5, teletherapy will be used with 
participants communicating with interventionists remotely (see Table 1), using their personal or a lab 
provided smartphone, a personal or lab provided computer/tablet, and a HIPAA compliant platform (e.g., 
Zoom). Due to the ongoing coronavirus pandemic, we will be conducting the intervention primarily 
through remote means to account for the safety of and to reduce close and direct in-person contact 
between personnel and participants. Remote sessions are also in place to increase the ecological validity 
of the intervention. Teletherapy for the majority of intervention sessions will allow for participants to meet 
with their assigned respiratory and SCT therapists online from a private, internet secure location of their 
choosing to complete intervention sessions.
Five remote respiratory training sessions and four remote SCT sessions will occur. During HRVB 
respiratory training sessions, participants will be instructed to use the Inner Balance device and 
smartphone applications while simultaneously sharing their screen via Zoom while additionally attending 
the Zoom session on their laptop or tablet. Therapists will provide real time feedback and instruction 
during the session while assessing their progress via screenshare and while viewing the participant 
through their laptop/tablet. SCT sessions will also occur via Zoom. 
Table 1. Summary of Integrated HRVB-SCT Intervention Protocol by Session
Week
Session
Core Components
Time
Pay
Screener
●
Consent, questionnaires, assess abstinence 
via CO scheduling, set quit date
Week 1aL
(Baseline)
IA

Recording session: Baseline, Plain Vanilla, 
Dot Tracking
30
50
$35 (if 
ineligible)
SCT S1
●
SCT program introduction and orientation to 
Clear Pathways
●
Goals: Understanding why you smoke, 
health effects of smoking/quitting, reasons to 
quit, assess and build confidence
30
HRVB S1
●
Intervention Overview
●
Recording session
●
Goal: Introduce HRVB Breathing using pacer 
and Inner Balance
60
(Session 
1)
EMA

Introduction/enrollment to homework
$10
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SCT S2
●
Goals: Review quit date, plan for quit day 
(week 2), troubleshoot potential barriers to 
quitting
●
Introduce NRT and instructions on how to 
use the patch
30
HRVB S2
●
Biofeedback practice session
●
Goal: Introduce biofeedback
●
Assign homework: Practice 4x/day for at 
least 20m
30
Week 1bV
EMA

Assess homework compliance and surveys 
cravings, withdrawal, distress, and relaxation 
symptoms
$10
SCT S3
●
Review homework
●
Goals: Continue to discuss and revise quit 
plan, monitor motivation to quit, trouble-
shoot/learn from failures
30
Week 2V
(Quit Day)
HRVB S3
●
Biofeedback practice session 
●
Goal: Review and adjust Inner Balance 
HRVB
●
Assign homework: Practice 4x/day for at 
least 20m
30
$10
EMA

Assess homework compliance and surveys 
cravings, withdrawal, distress, and relaxation 
symptoms
up to $105 for 
HW practice
SCT S4
●
Review homework
●
Goals: Highlight successes, troubleshoot 
potential barriers to quitting, preventing 
relapse
●
Assess NRT use side effects, 
questions/concerns, adherence 
30
Week 3V 
(1W post-
quit)
HRVB S4
●
Biofeedback practice session 
●
Goal: Review and adjust Inner Balance 
HRVB
●
Make post-quit adjustments to HRVB, assess 
adherence, motivation
●
Assign homework: Practice 4x/day for at 
least 20m
30
$10
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EMA

Assess homework compliance and surveys 
cravings, withdrawal, distress, and relaxation 
symptoms
up to $105 for 
HW practice
SCT S5
●
Review homework
●
Assess abstinence status, revise quit plan to 
maintain abstinence or resume cessation, 
●
Provide additional NRT 
30
Week 4V
(2W post-
quit)
HRVB S5
●
Biofeedback practice session 
●
Goal: Assess adherence, motivation, trouble-
shoot 
●
Assign homework: Practice 4x/day for at 
least 20m
30
$10
EMA

Assess homework compliance and surveys 
cravings, withdrawal, distress, and relaxation 
symptoms
up to $105 for 
HW practice
HRVB S6
●
Biofeedback practice session 
●
Goal: Assess adherence, motivation, trouble-
shoot 
●
Assign homework: Practice 4x/day for at 
least 20m
30
$10
Week 5V 
EMA

Assess homework compliance and surveys 
cravings, withdrawal, distress, and relaxation 
symptoms
up to $105 for 
HW practice
IA
●
1MFU Survey 
●
Recording session: Baseline, Plain Vanilla, 
Dot Tracking 
50
SCT S6
●
Assess quit status via CO analysis
●
Goal: Assess abstinence status, offer of 
support, encourage resumption, provide 
additional NRT 
30
Week 6L
(1M post-
quit)
HRVB S7
●
Recording session 
●
Goal: obtain commitment to continue practice
30
$35
EMA

Assess homework compliance and surveys 
cravings, withdrawal, distress, and relaxation 
symptoms
up to $105 for 
HW practice
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IA
●
Assess abstinence via CO and cotinine
●
Recording session: Baseline, Plain Vanilla, 
Dot Tracking
60
Week 15L 
(3M post-
quit)
Research 
Coordinat
or
●
3MFU survey, Exit interview
30
$50 for 
attending 3 
mo F/U
$50 bonus for 
attending 6/7 
sessions
LIn-lab intervention session; VVirtual intervention session
Participants will be paid up to $15 each day for past week at-home breathing practice during HRVB 
sessions 3, 4, 5, 6, and 7, corresponding with weeks 2-6. Specifically, participants will be paid $5 for their 
first at-home practice lasting at least 5-minutes on a given day, $5 for their second at-home practice 
lasting 5-minutes, and $5 for any additional at-home practice lasting at least 5 minutes. Practice will be 
verified via the Inner Balance app, which records practice sessions, and the Metricwire app. In order for 
participants to be eligible for homework compensation, a practice session must last a minimum of 5 
minutes, and they must complete pre- and post-ratings of craving, withdrawal, relaxation and distress. 
Table 2. Study Measures Table
PS
BL
W
Q
2W
1M
3M
Phone Screen:
Interview: The phone screen will be administered prior to study 
enrollment to help determine whether interested participants are 
eligible.
X
Readiness to Quit Ladder: Single-item measure that includes ten 
response options that assess motivation to quit along a continuum.  
Options range from 10, “I have quit smoking and I will never smoke 
again”, to 1, “I enjoy smoking and have decided not to quit smoking for 
my lifetime.  I have no interest in quitting”.  As such, higher scores on 
this measure indicate higher readiness to quit (Biener et al., 2003).
X
Risk Assessment: Study personnel will receive extensive training in 
risk assessment and follow the attached protocol should a potential 
participant or consented participant indicate suicidality/homicidality or 
extreme distress.
X
Covid-19 Screening: Study personnel will assess participants for 
recent positive Covid-19 test results, developing Covid-19 related 
symptoms, and recent exposure to others who may have tested 
positive for Covid-19. This screening is conducted to ensure the health 
and safety of both participants and study personnel.
X
The Mini International Neuropsychiatric Interview 7.0.0 (MINI): 
Semi-structured interview guide for making the major DSM-5 
diagnoses. Sections C, I, J, and K  are administered to screen for 
Mood, Psychotic, and Substance Use Disorders. The MINI can be used 
to make diagnoses either categorically (absent or present) or 
dimensionally (Sheehan et al., 1998).
X
In Person, Virtual Interview, and 
Qualtrics Measures:
Participant Information Sheet: Questionnaire used to confirm 
X
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inclusion/exclusion criteria.
Medical Screening Questionnaire: Questionnaire used to confirm 
inclusion/exclusion criteria.
X
Participant Contact Info: Used to document best means to contact 
participant for study communication (includes request for permission to 
text).
X
Demographic Information: Used to confirm inclusion/exclusion 
criteria.
X
MacArthur Scale of Subjective Social Status: Single-item measure 
that assesses a person’s perceived rank relative to others in their 
group. Participants view a drawing of a ladder with 10 rungs and 
identify which rung reflects their perceived status based on the 
description provided (Adler, Epel, Castellazzo, & Ickovics, 2000).
X
Smoking History Questionnaire (SHQ): 30-item questionnaire used 
to assess participants smoking history and patterns of use.  Items 
pertain to smoking rate, age of onset of smoking initiation, and years 
being a daily smoker (Brown et al., 2002).
X
Fagerström Test of Cigarette Dependence (FTCD): 7-item scale use 
to evaluate the quantity of cigarette consumption, the compulsion to 
use, and nicotine dependence. The measure has both yes/no items 
(scored as 1 or 0) and multiple-choice items (scored from 0-3).  These 
scores are then summed to give a total score from 1-10 where the 
higher the score the more intense the subject’s nicotine dependence is 
(Fagerström, 1978 & 2012).
X
X
X
X
Brief Wisconsin Inventory of Smoking Dependence Motives 
(WISDM-34): 34-item self-report questionnaire which assesses 
theoretically-derived motivational domains of smoking across 13 
subscales that have acceptable internal consistency, are differentially 
present across levels of smoking heaviness, and have multi-
dimensional structure. Participants use 7-point Likert scale(1=not at all 
true of me to 7=extremely true of me) to indicate nicotine dependence. 
Its reliability and validity has been proven to be good (Stevens et al., 
2010). 
X
X
X
Difficulties in Emotion Regulation Scale (DERS): 36-item, self-report 
scale that assesses multiple aspects of emotional dysregulation.  The 
measure includes 6 subscales, Nonacceptance (When I’m upset, I feel 
guilty for feeling that way), Goals (When I’m upset, I have difficulty 
concentrating), Impulsivity (When I’m upset, I lose control over my 
behaviors), Awareness (I am attentive to my feelings; reverse coded 
item), Strategies (When I’m upset, I believe that I’ll end up feeling very 
depressed), and Clarity (I have difficulty making sense out of my 
feelings).  All items are score on a 5-point scale, where 1 = almost 
never (0-10%) and 5 = almost always (91-100%).  The measure also 
yields a global score (Gratz & Roemer, 2004).
X
X
X
Smoking and Weight Eating Episodes Test (SWEET): 10-item, self-
report measure used to assess the extend to which individuals smoke 
for specific reasons related to eating and weight concerns. Responses 
are rated on a 5-point Likert scale ranging from (1) never to (5) always. 
This scale has demonstrated good psychometric properties and has 
been validated in male and female daily cigarette smokers (Adams et 
al. 2011; Farris et al. 2018)
X
X
X
Distress Tolerance Scale (DTS): 15-item scale used to assess 
participants’ perception of their ability to tolerate mental distress. Items 
X
X
X
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(e.g. “I can’t handle feeling distressed or upset”) answered on 5-point 
Likert-type scales ranging from (1) strongly agree to (5) strongly 
disagree evaluate participants’ ability to experience and endure 
negative emotional states and includes scales that assess appraisal, 
tolerance, absorption, and regulation. This scale contains good 
psychometric properties, including high internal consistency (Simons & 
Gaher, 2005).
The Urgency, Premeditation, Perseverance, and Sensation 
Seeking Impulsive Behavior (UPPS-P): 20-item measure used to 
assess characteristics of personality, such as how rashly participants 
respond in response to negative moods, and determines how they may 
contribute to impulsive behavior. Items are rated on a 4-point Likert-
type scale (1 = Agree Strongly to 4 = Disagree Strongly) to indicate 
how much each statement applies to them. The scale demonstrates 
good internal consistency and convergent and divergent validity 
(Whiteside & Lynam, 2001; Cyders, Smith, Spillane, Fischer, Annus, & 
Peterson, 2007).
X
X
X
Somatic Symptoms List (SSL): 30-item measure of fear of non-
anxiety-related sensations (It scares me when I have an earache). 
Items are rated on 5-point Likert scale ranging from very little to very 
much and show good internal consistency (Norton, & Edwards, 2015).
X
X
Nicotine Dependence Syndrome Scale (NDSS): 19-item 
questionnaire designed to yield continuous measures of multiple 
theoretically-derived dimensions of dependence. It yields scores for (a) 
Drive, which captures craving and withdrawal and the subjective sense 
of compulsion to smoke; (b) Priority, the behavioral preference of 
smoking over other reinforces; (c) Tolerance, reduced sensitivity to 
smoking’s effects; (d) Continuity, the regularity of smoking; and e) 
Stereotypy, the rigidity of smoking patterns and tendency to smoke in 
the same way regardless of circumstances. It also yields a single 
summary score (NDSS-T) for dependence. The scale has been 
validated in adult population and treatment samples, and validated 
variations are available for teen smokers (Shiffman, Waters, & Hickcox, 
2004).
X
X
The Pittsburgh Sleep Quality Index Scale (PSQI): 19 item self-rated 
questionnaire used to assess sleep quality and disturbances over a 1-
month time interval. These 19 items are grouped into seven 
components that reflect standardized areas routinely evaluated in 
clinical assessments with patients who report sleep/wake complaints: 
subjective sleep quality, sleep latency, sleep duration, habitual sleep 
efficiency, sleep disturbances, use of sleeping medications, and 
daytime dysfunction. Items are equally weighted and rated on a 0 to 3 
scale (0=no difficulty to 3=severe difficulty). The seven component 
scores are summed to produce a global score (range 0 to 21), with 
higher scores indicating worse sleep quality. The clinimetric and clinical 
properties of the PSQI (acceptable internal homogeneity, consistency, 
and validity) support its use in psychiatric clinical practice and research 
activities (Buysse et al., 1988).
X
X
X
Multidimensional Assessment of Interoceptive Awareness (MAIA): 
32 item measure that assesses multiple dimensions of interoception by 
self- report (Mehling, Price, Daubenmier, Acree, Bartmess, & Stewart, 
2012).
X
X
X
The Intolerance for Smoking Abstinence Discomfort (IDQ-S): 17-
X
X
X
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item questionnaire to assess the participants ability to tolerate the 
acute discomforts of recent smoking abstinence. The subscales 
measure Withdrawal Intolerance (12-items) and Lack of Cognitive 
Coping (5-items). Items are rated on a Likert scale ranging from 1= 
strongly disagree to 5 = strongly agree. The mean of all items is used 
for the total score for each scale (Sirota, Rohsenow, MacKinnon, 
Martin, Eaton, Kaplan, & Swift, 2010).
Body Vigilance Scale: 4 item measure that assesses a respondent’s 
degree of sensitivity to internal bodily sensations such as palpitations 
or dizziness. Respondents indicate on an 11-point Likert Scale (0 = 
none to 10 = extreme) (Schmidt, Lerew, & Jackson, 1997).
X
X
X
Boredom Susceptibility Subscale: 10-item yes/no subscale of the 
Sensation Seeking Scale used to assess susceptibility to boredom 
(Zuckerman & Link, 1968).
X
X
X
Mindful Attention Awareness Scale: 15-item scale used to assess 
dispositional mindfulness, specifically, open or receptive awareness of 
and attention to what is taking place in the present (Brown & Ryan, 
2003).
X
X
X
Fagerstrom Test for Nicotine Dependence: 6 item measure that 
assess the intensity of physical addiction to nicotine. The items 
measure the quantity of cigarette consumption, the compulsion to use, 
and dependence. The yes/no items are scored from 0 to 1 and the 
multiple-choice items are scored from 0 to 3 (Fagerstrdm, 1978).
X
X
Sensitivity to COVID-19 Health Symptoms Scale (SCHSS): 14-item 
scale used to measure physical symptoms Covid-19 related anxiety. 
X
Fear of Coronavirus-19 Scale: 7-item scale used to measure physical 
and psychological symptoms of Covid-19 related fear (Ahorsu et al., 
2020).
X
COVID-19 Stress Scales: 36-item measure designed to assess 
COVID-19 related stress and worry that occurred in the past 7 days. 
Items are split into 6 sub-scales: Danger (I am worried about catching 
the virus), Socioeconomic consequences (I am worried about grocery 
stores running out of food), Xenophobia (I am worried that foreigners 
are spreading the virus in my country), Contamination (I am worried 
that people around me will infect me with the virus), Traumatic stress (I 
had trouble sleeping because I worried about the virus), and Checking 
(Social media posts concerning COVID-19). Participants answer along 
a 5-point Likert scale (Taylor et al., 2020).
X
Pre, Mid, and Post-Intervention Acceptance and Feasibility Ratings 
(Participant and Therapist versions): Participants will be asked to 
provide ratings of intervention helpfulness, intervention satisfaction, 
commitment, negative feelings during session, and degree of difficulty 
understanding intervention content. Therapists will report incidences of 
technological issues, distractions in participant remote environment and 
their respective influence on treatment delivery.
X
X
X
Carbon Monoxide Analysis of Breath Sample: CO analysis will be 
used to verify eligibility and abstinence status. Analysis will rely on the 
Bedfont handheld piCO Smokerlyzer and iCOquit Smokerlyzer, which 
will be used for in-person and remote verification, respectively.
X
X
X
X
Daily Information Sheet: Details participants’ cigarette use, alcohol 
consumption, substance use, medications, meals consumed, and NRT-
related side effects  
X
X
X
X
X
X
Craving/Withdrawal Visual Analog Scale (CW-VAS): Measures 
craving as well as the severity of withdrawal symptoms ranging from 0 
X
X
X
X
X
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(none or non-existent) to 100 (extreme).
Timeline Followback:  Used to assess ongoing cigarette, e-cigarette, 
patch, alcohol, and other tobacco and substance use (Sobell & Sobell, 
1992 & 1995).
X
X
X
X
X
X
Positive and Negative Affect Schedule: Used to assess current 
emotional states before and after intervention sessions (Watson & Clark, 
1988 & 1999).
X
X
X
X
X
X
Felt Arousal Scale (FAS): Used to measure activation on a 6-point 
scale from low (1 point) to high arousal (6 points) (Svebak & 
Murgatroyd, 1985).
X
X
X
X
X
X
Distress Intolerance Index: Used to assess participants’ perceptions 
of their ability to tolerate mental distress (McHugh & Otto, 2011).
X
X
X
Short-form Health Survey (SFH): Used to assess quality of life in 
regard to health (Ware, Kosinski, & Keller, 1996).
X
X
X
X
X
Thoughts about Abstinence: Used to assess commitment to 
complete abstinence including importance and confidence (Hall, 
Havassy, & Wasserman, 1991).
X
X
X
X
X
Barriers of Cessation Scale:19-item scale that is made up of three 
subscales: 1) Addiction Barriers scale (“Fear of failing to quit”), 2) 
External Barriers subscale (“No encouragement of help from friends”), 
3) Internal Barriers subscale (“Feeling less in control of your moods”).  
The scale also includes a “gaining weight” item.  The score scale 
ranges from 1 to 3, where 0 = not a barrier/not applicable and 3 = large 
barrier (Macnee & Talsm, 1995).
X
X
X
X
X
Minnesota Nicotine Withdrawal Scale: Used to measure the urge to 
smoke (craving), depressed mood, anxiety, irritability, frustration, or 
anger, concentration levels (Cappelleri, Bushmakin, Baker, Merikle, 
Olufade, & Gilbert, 2005).
X
X
X
X
X
Depression Anxiety Stress Scale (DASS-21): Used to assess past 
week symptoms of depression, anxiety, and stress (Henry & Crawford, 
2005).
X
X
X
X
X
Questionnaire of Smoking Urges: 10-item questionnaire reflecting 
strong desires or intention to smoke, as well as anticipation of relief 
from negative affect with desire to smoke (Cox, Tiffany, & Christen, 
2001).
X
X
X
X
X
Anxiety Sensitivity Index 3 (ASI-3): 18-item measure that assesses 
the basic dimensions of anxiety sensitivity: fear of physical symptoms 
(When my throat feels tight, I worry that I could choke to death), fear of 
cognitive symptoms (It scares me when I am unable to keep my mind 
on a task), and fear of publicly observable symptoms (I think it would 
be horrible for me to faint in public).  Responses can range from 0 = 
very little, to 4 = very much (Taylor et al., 2007).
X
X
Frustration Discomfort Scale (FDS): 35 item measure to assess 
participants’ intolerance of distress or frustration. Items represent 
potential beliefs which participants may possess (e.g., “I can’t stand 
having to persist at unpleasant tasks”) and are rated on a 5-point 
Likert-type scale (1 = absent to 5 = very strong). Internal reliability, 
divergent validity, and discriminative validity are supported (Harrington, 
2005).
X
X
Dot Tracking Task: Will be used to manipulate participants’ attentional 
demands. During this task, participants are presented with 12 dots on a 
computer screen, 3 of which are initially yellow, and 9 of which are 
gray. The yellow dots subsequently turn gray, and all the dots move at 
X
X
X
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random around the screen. When they come to a stop, participants are 
to remember which dots were initially yellow. There are a total of 12 
trials that increase in difficulty. During the task, respiration, pulse 
plethysmograph, heart rate and cardiac output are continually 
assessed. The change in these parameters from resting to that 
observed during dot tracking serves as an assessment of change in 
parasympathetic and sympathetic nervous system activation as a 
function of attentional demands. The construct indexed, vagal flexibility, 
is linked to the ability to adaptively respond to stress (Muhtadie, Koslov, 
Akinola, & Mendes, 2015).
Smoking Abstinence Expectancies Questionnaire (SAEQ): 28-item 
self-report questionnaire evaluates the the expected short-term 
psychological and physiological consequences of abstaining from 
smoking. Full-scale and subscale (Negative Mood, Somatic Symptoms, 
Harmful consequences and Positive Consequences) scores exhibit 
good internal consistency, convergent and discriminant validity, and 
test-retest reliability (Abrams, K., Zvolensky, M., Dorman, L., Gonzalez, 
A., & Mayer, M. (2011). 
X
X
Barkley Deficits in Executive Functioning Scale-Short Form 
(BDEFS-SF): 20-item short form of the BDEFS assessing daily 
executive functioning, such as self-regulation of emotions and time 
management. Participants will use a 4-point Likert-type scale (1 = 
never or rarely to 4 = very often) to indicate how often they experience 
each statement (e.g., “Make impulsive comments to others“). This 
scale has demonstrated good reliability and validity (Barkley, R. A. 
(2011). 
X
X
5-Trial Adjusting Delay Task: a novel method of obtaining a delayed 
discount rate in less than 1 minute such that participants answer only 5 
questions as a result of branch logic which generates individually 
tailored choice options from 31 possible items (Koffarnus, M. N., & 
Bickel, W. K. (2014). 
X
X
Adult ADHD Self-Report Screening Scale (ASRS-5): 6-item measure 
that is short, easily scored, and can detect the vast majority of adult 
attention-deficit/hyperactivity disorder cases in the general population 
with high sensitivity and specificity. The scale has excellent cross-
validated concordance with blinded clinical diagnoses of DSM-5 adult 
attention-deficit/hyperactivity disorder (Kessler, et al., (2005). 
X
X
Perceived Stress Scale (PSS10): 10 item measure designed to 
assess stress perceptions on a 5-point Likert scale ranging from 0 = 
never to 4 = very often. Items were designed to tap how unpredictable, 
uncontrollable and overloaded respondents find their lives. Construct 
validity, internal reliability and predictive reliability are supported 
(Cohen, S., & Williamson, G. (1988). 
X
X
Cigarette Purchase Task (CPT): 26-item measure used to assess trait 
demand for cigarettes or the behavior-maintaining properties of 
nicotine. Participants report the number of hypothetical cigarettes they 
would purchase for consumption across varying prices (i.e. $0.00-
9.00). This results in a curve that represents the relationship between 
the demand for cigarettes and escalating price. The demand curve is 
comprised of the following indices: intensity (number of cigarettes 
consumed at unrestricted cost), breakpoint (price at which consumption 
is suppressed to zero), Omax (peak expenditure for cigarettes), Pmax 
(the price at maximum expenditure for cigarettes), and elasticity (the 
degree to which consumption decreases with increasing price) 
X
X
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(MacKillop, et al., (2008) 
Exit Interview: Used to collect information about the participant’s 
understanding of the rationale for the intervention, the degree to which 
the information was applicable and relevant, and their overall feedback 
and thoughts on the intervention to inform adjustments to the 
subsequent R01 trial.
X
Cotinine Sample: Biochemical verification of smoking abstinence will 
support point prevalence abstinence at the 3m follow-up via the 
Salimetrics Enzyme Immunoassay Salivary Cotinine Kit.
X
Ratings of Session Protocol Adherence and Examination of 
Physiological Data for Intervention Accuracy: Recorded sessions 
will be coded in order to assess accuracy of intervention delivery.
X
HRVB and SCT Clinician Training and Supervision: Clinicians will receive a minimum of 8 hours of 
training from study investigators in the application HRVB and will have to complete a minimum of 5 
practice sessions prior to seeing participants. Clinicians will be approved for the study following careful 
assessment of their protocol adherence, competent application of skills, by the PI. Clinicians will have to 
demonstrate general knowledge in appropriately modifying HRVB for participants, navigating and 
addressing common barriers (e.g., discomfort, dizziness), addressing motivation and adherence, 
instructing and monitoring participants both in-lab and virtually, and will role-play managing several 
common issues that arise during HRVB before they are assigned participants. Fidelity data will be 
collected via independent evaluators who will use an HRVB-specific rating scale to assess protocol 
adherence, implementation of strategies and skills in-session. Designated study assessors will be asked 
to code audio-recordings, specifically, 25% of the initial eight HRVB sessions provided to participants will 
be coded (Muse & McManus, 2013). Fidelity will additionally be assessed by Co-I  Farris who will review 
recorded physiological data from baseline and 3-month follow up to rate whether participants, under 
therapist instruction, received adequate resonance between heart rate and blood pressure, central to the 
success of the intervention. Measures of treatment fidelity are critical to the current proposal given it has 
never been applied to smokers and requires ongoing monitoring of participant behavior and physiology. 
For example, slow-paced breathing is sometimes accompanied by compensatory changes in breath 
depth, a process that can inadvertently decrease end tidal carbon dioxide (etCO2), which is 
contraindicated and will not result in desired RSA oscillations; clinicians will need to know how to identify 
and remedy contraindicated breathing patterns, such as hyperventilation, both during in-lab and remote 
sessions, to promote accurate HRVB application. 
Clinicians will additionally receive at least 5 hours of training in the delivery of SCT. SCT training will 
include psychoeducation regarding the prevalence of smoking, common beliefs about smoking and 
cessation, as well as specific training in the co-occurrence of depression and anxiety in smokers and 
implications for intervention. Clinicians will be trained in the administration of the adapted manual, 
teaching of skills to participants, conducting the intervention in-lab and virtually, and how to develop 
personalized smoking cessation plans. Clinicians will complete several role play sessions so that they are 
equipped with the various issues that commonly impede smoking cessation, and how to appropriately 
respond. In addition to training, clinicians will be asked to record a minimum of 3 practice sessions. Prior 
to being approved for the study, the PI will review for adherence to the study protocol and determine if 
additional training is needed. All clinicians will be provided with additional feedback following review of 
recorded sessions. 
Clinical supervision will occur on a weekly basis with the PI for 2 hours. The first hour will be spent 
reviewing HRVB sessions, and the second hour will be spent reviewing SCT sessions. The purpose of 
supervision is to provide additional training and support to clinicians to ensure fidelity of the intervention. 
In addition, issues regarding homework compliance and participant retention will be addressed.
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Potential Problems and Alternative Strategies: Clinicians will be trained to be flexible in HRVB 
application depending on the needs of the patient. For example, additional use of the pacer or 
biofeedback may be indicated for an individual who is struggling with appropriate respiratory pacing or 
achieving maximal oscillations, respectively. Alternatively, both strategies may be abandoned, and the 
clinician may choose instead to focus on breath depth and quality, if a patient is experiencing difficulty 
with hyperventilation (e.g., decreases in expired tidal volume of CO2). Because at-home practice is critical 
to the promotion of long-term improvements in vagal cardiac activity, the first two weeks will include both 
an in-person and virtual training session. To address adherence, we have put in place several strategies. 
Participants who do not have smart phones will be given one for use during the duration of the study. At-
home practice will be characterized as a tool that participants may use in place of smoking. In this 
manner, participants may begin to reduce smoking and conceptualize practice as a helpful skill, rather 
than a time-consuming task. Such an approach is bolstered by the ease of use of the phone app, which is 
discreet, on their person, and will serve as a practice cue. To test feasibility of the intervention, without 
offering additional incentive, our participants will not receive additional adherence reinforcement. 
In accord with clinical practice guidelines, participants will begin NRT on the morning of their quit date and 
will be provided with a full 8-week course (Fiore et al., 2008). This will ensure that assessment of ANS 
parameters just prior to the quit day is not confounded. Participants will not complete their taper until the 
end of week 6; this will allow for adequate washout of plasma nicotine, allowing us to biochemically verify 
abstinence and examine additional cardiac vagal tone changes as a function of treatment.
The ongoing COVID-19 pandemic places all research in an unpredictable situation. We anticipate that we 
may experience challenges in recruitment and retention associated with illness or safety concerns that 
could affect both study personnel and participants. We will address these issues on an ad hoc basis, for 
example, by subbing in respiratory therapists when possible, permitting participants to do make-up 
sessions, collecting in-person data at modified times, etc., and carefully documenting each adjustment 
made. Also, a growing body of empirical work has documented the extensive effects of the pandemic on 
mental health, including emotional distress and substance use. We have added several questionnaires, 
both validated quantitatively and qualitatively, to obtain information regarding the effects of the pandemic 
on mental health and functioning, as well as information regarding personal COVID-19 related 
experiences (e.g., disease contraction by self or close contact). Collection of this data will help the study 
team glean whether any related effects, or lack thereof, or differences in outcomes between Stage 1A 
and 1B may be attributable to the pandemic. 
Transition to a remote intervention introduces several concerns related to intervention fidelity. Although 
the Inner Balance device provides relatively reliable real time HRVB feedback, therapists cannot view the 
participant and their physiology simultaneously. This may introduce challenges in determining whether 
the participant is practicing the intervention correctly and troubleshooting difficulties they are 
experiencing, such as feeling breathless or lightheaded. To address these concerns, the baseline 
appointment includes extensive training in the intervention and orientation to using the Inner Balance 
device and the Zoom mobile and computer software, so that participants can swiftly move between 
screens when working with their respiratory therapist remotely. Also, it is possible that the intervention 
may be disrupted due to connectivity problems. In the event this occurs, a backup plan, including the use 
of other HIPAA compliant platforms (e.g., Microsoft Teams), will be enacted, or the session will be moved 
to traditional audio phone call or rescheduled. 
Compensation: Participants will receive up to $755 in total study compensation. This includes $10 per 
week for general participation, $35 for baseline and 1-month follow-up appintments, $50 for their 3-month 
follow-up appointment, a $50 bonus for attending at least 6 out of 7 sessions. Additionally, subjects will be 
paid up to $105 each week for at home breathing practice from weeks 2-6.
B.
Data Points
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Data will be collected over the course of 15 weeks, which include 3 in-person laboratory sessions 
and 5 remote sessions (see Table 1 ), and will include interview, self-report, behavioral, and 
psychophysiological assessment.  
C.
Study Duration
Following the baseline and first session, which will last 1-3 hours, participants will be asked to 
complete 6 additional intervention sessions over the course of 6 weeks, lasting 30-60m each. 
They will also be asked to complete a final follow-up appointment, which corresponds with 3-
months post their quit date. 
D.
Endpoints
N/A
1.4 Preliminary Data
Complete reporting of preliminary data collected during the Pilot Phase IA of this trial can be found under 
the eIRB protocol Pro2018001848. Of particular relevance for the current protocol, feasibility findings from 
the preliminary Phase 1A of this study suggest the previous in-person structure could be improved. Primary 
Phase IA outcome measures assessing intervention feasibility included participant attendance and ratings 
of the intervention’s efficacy, appropriateness of fit, and ease of use in daily life. All scale scores ranged 
from 0=completely disagree to 4=completely agree. Intervention acceptability also served as a primary 
outcome and was assessed via participant ratings of intervention satisfaction and liking. Of the seven 
participants who remained in treatment beyond the first session, an average of 8.71 (SD= 1.49) treatment 
sessions were attended. At the 3-month follow-up visit, participant average ratings of the intervention’s 
efficacy, appropriateness, ease of use, and acceptability were 3.19 (SD=0.52), 2.87 (SD=0.75), 1.58 
(SD=0.32), and 3.52 (SD=0.31), respectively. While the intervention was high in efficacy, appropriateness, 
and acceptability, these initial results suggest the intervention was not perceived as being easily integrated 
into participant’s daily lives. With this in mind, an intervention protocol modified for predominantly remote 
instruction may facilitate in addressing this previous feasibility limitations (see Feasibility section 4.3C for 
further detail). 
 
1.5 Sample Size Justification
Given the developmental nature of the project, our sample size was selected to obtain a reasonable 
estimate of treatment feasibility, acceptability, and efficacy that would be critical to supporting a future 
R01 clinical trial. We enrolled n=10 participants for phase 1A and plan to enroll n=30 for phase 1B. 
Statistical power for phase 1B was determined using G*Power 3.1.9. and based on the analytic approach 
for examining our secondary outcomes of interest. Separate paired sample t-tests will be used to examine 
within-subject differences in the number of cigarettes smoked per day and in emotional distress from pre-
treatment baseline, 1-month post-quit, and 3-month post-quit, respectively. Paired sample t-tests 
determined that at a power of 80%, α=0.25, an N=30 is sufficient to detect a small to medium-sized effect 
(Cohen’s d=0.40). A Type I error rate of .25, has been suggested as an adequate error rate for testing 
preliminary pilot study effects and can be used to inform a more comprehensive study, including sample 
size planning for a future Stage II R01 (Moore et al., 2011). Given our relatively short assessment phase, 
this may still be too conservative estimate. Therefore, we will carefully examine effect size estimates and 
pursue a larger trial if a small to medium effect is observed.
1.6 Study Variables and Outcomes
To inform a subsequent clinical trial, our analytic plan focuses on the use of descriptive and inferential 
statistics.
Primary Outcomes: 
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Aims 1.a. and 1.b.: Feasibility and Acceptability: 
Descriptive statistics will be used to assess feasibility and acceptability of HRVB (see 1.a. Intervention 
feasibility and 1.b. Intervention acceptability). Ratings of perceived effectiveness, appropriateness, 
satisfaction, and ease of the intervention are made on a 5-point Liker-type scale ranging from 
0=completely disagree to 4=completely agree.  Descriptive statistics will also be used to assess 
participant attendance, adherence, indexed by time spent using the intervention. Instances of 
technological limitations will be indexed both by count as well as qualitative descriptors (e.g., inner 
balance device failure to pick up recording; Bluetooth connection errors, etc.).
Secondary Outcomes: 
Aim 2.a: Changes in smoking behavior: 
Descriptive statistics will be used to report total number and percent of participants reporting abstinence 
on their quit day using the intent-to-treat sample as well as those who remain in treatment. 
Sustained smoking cessation will be assessed descriptively using point prevalence abstinence defined 
by self-reported abstinence verified by both carbon monoxide analysis of breath sample and saliva 
cotinine. Paired sample t-tests will be used to assess changes in smoking rate within participants from 
baseline to quit day, two-week, one-month, and three-month follow-up, as a proxy for harm reduction. 
Aim 2.b.: Changes in emotional distress: 
Paired sample t-tests will be used to assess changes in emotional distress, including depression, 
anxiety and stress, within participants, from baseline to two-week, one-month, and three-month follow-
up. 
We will also examine correlations between baseline emotional distress ratings and key outcomes, 
including feasibility and acceptability ratings, changes in smoking behavior, and emotional distress to 
evaluate whether the intervention may be particularly beneficial for smokers with elevated emotional 
distress,
The following list of measures will be used to assess primary and secondary outcomes of interest: 
1.a: Intervention feasibility 
Outcome
Method
Time Frame
Participant Attendance
Number of attended sessions out of 7 possible 
sessions 
7 weeks 
Practice Adherence 
Time (in minutes) spent practicing the breathing 
intervention 
7 weeks 
Intervention 
Effectiveness 
Participant self-report items assessing how effective 
the intervention was in helping participants quit and 
manage emotional distress  
Week 1 (i.e., treatment initiation) 
and Week 16 (i.e., 3-MFU)
Intervention 
Appropriateness 
Participant self-report items assessing intervention 
comprehension and fit 
Week 1 (i.e., treatment initiation) 
and Week 16 (i.e., 3-MFU)
Intervention Ease 
Participant self-report items assessing ease of use 
and fit into daily lifestyle 
Week 1 (i.e., treatment initiation) 
and Week 16 (i.e., 3-MFU)
Technological 
Limitations 
Interventionist self-report items assessing incidences 
of technical issues and related effects on intervention 
delivery 
7 weeks 
1.b. Intervention acceptability 
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Outcome
Method
Time Frame
Satisfaction and Liking 
Self-report items assessing satisfaction with learning 
the intervention, liking the intervention, breathing 
techniques, nicotine replacement, and recommending 
the intervention to others 
Week 1 (i.e., treatment initiation) 
and Week 16 (i.e., 3-MFU)
2. Secondary Outcome Measures: 
2.a. Changes in smoking behavior 
Outcome
Method
Time Frame
Quit-day abstinence
Self-reported abstinence on Quit Day, verified with 
carbon monoxide analysis of breath sample (CO < 
8ppm)
Week 3 (i.e., Quit Date) 
Sustained Smoking 
Cessation 
Self-reported abstinence, verified carbon monoxide 
analysis, and salivary cotinine (<10 ng/mL) at study 
termination
Week 16 (i.e., 3-MFU)
Smoking rate
Timeline Followback interview assessing changes in 
smoking rate
Week 0 (i.e., Baseline,) Week 3 
(i.e., Quit Date), 5 (i.e., 2-WFU), 
Week 7 (i.e.,1-MFU) and Week 16 
(i.e., 3-MFU)
2.b: Changes in emotional distress (i.e., anxiety, depression, and stress)
Outcome
Method
Time Frame
Emotional Distress   
Self-report items assessing past 2-week ratings of 
depression, anxiety, and stress 
Week 0 (i.e., Baseline,) Week 5 
(i.e., 2-WFU), Week 7 (i.e.,1-MFU) 
and Week 16 (i.e., 3-MFU)
1.7 Drugs/Devices/Biologics 
Nicotine replacement therapy:
NicoDerm Transdermal Patch. The transdermal nicotine patch is an FDA approved treatment for nicotine 
dependence. Patches are available over-the-counter (OTC) without a prescription. Patches are available 
in 7,14, and 21mg doses. 
Study participants will be provided with information written at a 6th grade level describing the proper use of 
the nicotine transdermal patch, including a description of common side effects. To minimize adverse 
events, we are excluding smokers with potential contraindications (see Participants section within 
Methods above).
 
A.
Drug/Device Accountability and Storage Methods
1.
Storage and accountability. We will store nicotine replacement therapy (NRT) in original packaging 
(patch: box containing 2-week supply) in locked cabinets in a room with locked doors at One Spring 
Street. We will document temperature of the room weekly using a min/max thermometer.
a.
Transferring medication. Trained research staff will arrange to transfer medication between 
research laboratory sites as needed. Coordinators will be the only people who transfer 
medication between sites if needed, arranging with one another to pick up or drop off the 
medication. 
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2.
Inventory. We will use an NRT inventory log to document the Lot # and Expiration date of each box 
of NRT.
3.
Dispensing NRT. We will use an NRT dispensing log to document which boxes of NRT are provided 
to which subjects (listed by subject number only), by whom, and on what date. We will not collect 
unused portions of the NRT because it is not common practice to specify a time limit by which 
participants are required to use the NRT.
1.8 Specimen Collection
A.
Primary Specimen Collection
Cotinine samples collected by study staff for verification of abstinence qualify as human material, 
and our study follows additional safety guidelines for collection, storage, and transportation, 
required by the Institutional Biosafety Committee. As part of this, we have a biosafety protocol in 
place, including a written Exposure Control Plan. In addition, study personnel are required to 
complete Biosafety Training Certification. In accord with Rutgers policies on biosafety, study staff 
follow a specific set of procedures when collecting, storing, and transporting samples for analysis 
off-site, which also serve to maintain completeness and accuracy. 
1.9 Data Collection
A.
Primary Data Collection
All copies of records, behavioral tests, audio and video recordings, and physiological data are 
linked to an arbitrary 3-digit 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. 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 and stored separately from the participant ID list. 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 is also protected by never associating a participant’s name 
with results in any published or otherwise publicly presented report. Demographic information 
(e.g., age, ethnicity, education, marital status) will be reported using averages and percentages 
computed over multiple participants and never reported at the level of individual participants. All 
data gathered during study appointments will be coded by arbitrary study identifiers and stored 
immediately. This includes paper/pencil, physiological, and audio and video recordings. Audio 
and video recordings collected using portable devices will be destroyed immediately once stored. 
Moreover, because audio and video files contain additional identifying information, they will be 
stored in separate password protected files from other self-report and physiological data, to add 
an additional layer of confidentiality.
Digital data will be kept indefinitely. The reason for this is that laboratory personnel may wish to 
engage in secondary data analyses in the future, which may require looking at original raw data. 
However, to ensure confidentiality, data will remain coded by an arbitrary study number. Data will 
also continue to be stored in a locked cabinet in a locked office. Data stored on computers will be 
double password protected. 
Data will be stored for all interested participants, regardless of eligibility, to ensure that 
participants previously deemed ineligible are not mistakenly re-screened. Sessions will include a 
diagnostic interview completed via Zoom call, the baseline session, we will obtain consent, verify 
inclusion/exclusion criteria, assess smoking status, obtain physiological measurements to assess 
baseline autonomic nervous system activity, and ask participants to complete a battery of self-
report measures online. The document linking the three-digit identification number to participant 
contact information will be maintained and stored on a secure computer. Only the PI and the 
trained study staff will have access to this document. No names or identifying information will 
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appear in any data or data collection materials for any of the studies. Data will be stored 
electronically on a secure computer. The only study documents that will contain participants’ 
names and identifying information are the informed consent, payment tracking forms, and excel 
document used to track interested participants. These forms will be handled exclusively by the 
project director and coordinator and stored in a locked file drawer in the laboratory, separate from 
the study ID list. All data will be stored securely for at least five years following any publication of 
the data. Paper data will be destroyed after 6 years.
1.10 Timetable/Schedule of Events
Due to the impact that the novel coronavirus (COVID-19) had on research, the proposed timetable 
of the study has changed. We are anticipating entering a no-cost extension, extending the project 
timeline from 36 months to 48 months. 
2.0 Project Management
2.1 Research Staff and Qualifications
      All study staff have received CITI training, Specific roles are detailed, below:
Graduate Research Assistants: Graduate students from the Ph.D. and Psy.D. programs will receive 
extensive training in evidence-based smoking cessation treatment and will serve as study clinicians 
and independent assessors. They will also assist the Research Coordinators in day-to-day activities. 
Research Coordinator(s): Isabel Cunha has received training in the protection of human subjects 
and have obtained extensive research experience working in clinical research settings, including both 
laboratory and intervention protocols. She and the graduate student Hannah Brinkman will be 
responsible for coordination of this trial, including the training and supervision of undergraduate 
research assistance, oversight of participants screening, scheduling, communications, participant 
compensation, dispensing NRT, data management, informed consent procedures, and collecting in-
person assessments. 
Key Study Personnel: Drs. Leyro and Farris will be responsible for clinical training and supervision 
of personnel. They will also provide general project oversight, including training in all study 
procedures, IRB correspondence, documentation of all adverse events, and data safety monitoring 
board communication. Consultants, Drs. Hall and McCarthy will provide additional consultation on 
training, recruitment, and retention strategies. Dr. Bates and consultant Dr. Lehrer will provide 
additional expertise in data management, in particular, data cleaning, scoring, and analysis of 
psychophysiological data. All study staff have expertise in conducting clinical trials, working with 
individuals suffering from mental illness, and substance use disorders.  
2.2 Research Staff Training
3
Study staff will undergo extensive (10-15 hours) training on all study procedures. PI will oversee 
training, which will include verbal description and behavioral demonstration. Staff will then be 
conducted through the study as mock participants, and then allowed to conduct the PI through the 
Table 4. Timeline for Proposed Research 
Goals 
Phase II recruitment with a target of 3/month. Final enrolled participant by end of March 2023, with 3-
month follow-up data obtained by end of June 2023.
Clean and score physiological, behavioral, and self-report data by July 2023. Conduct analyses for 
Aim 1 and Aim 2. Revise manual based on project findings; begin manuscript draft and R01 
application development.
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study to allow for sufficient practicing of necessary procedures. All study staff have previously 
administered all of the aforementioned techniques during prior investigations.
4
Training will also include careful assessment of clinician adherence, defined as using the correct 
skills, as well as competence, meaning, and how well the skills are implemented (Fairburn & Cooper, 
2011). All clinicians will be required to pass a general knowledge test assessing competency in 
appropriately modifying HRVB for participants, navigating and addressing common barriers (e.g., 
discomfort, dizziness), addressing motivation and adherence, navigating both in-lab and remote 
sessions, and will role-play several common issues that arise during HRVB, before they are assigned 
participants. In addition, an HRVB-specific rating scale will be used to assess implementation of 
strategies and skills in-session. Following assessment of implementation strategies, study clinicians 
will receive additional training and manual adjustments will be made. Measures of treatment fidelity 
are critical to the current proposal given it has never been applied to smokers and requires ongoing 
monitoring or participant behavior and physiology. For example, slow-paced breathing is sometimes 
accompanied by compensatory changes in breath depth, a process that can inadvertently decrease 
end tidal carbon dioxide (etCO2), which is contraindicated and will not result in desired RSA 
oscillations; clinicians will need to know how to identify and remedy contraindicated breathing 
patterns, such as hyperventilation, to promote accurate HRVB application. 
5
Study clinicians will receive intensive training from Drs. Leyro and Farris who will provide ongoing 
clinical supervision and consultation. In addition to prescribed study measures, clinicians will 
complete progress notes with their qualitative assessment of difficulties they experienced working 
with their participants, as well as self-report measures of the therapeutic alliance, and sessions will be 
video recorded. Notes, ratings, and recordings will inform weekly supervision. Participants will be 
asked to complete weekly pre- and post-session ratings of affect and treatment expectancy and 
credibility of intervention rationale. Finally, data will be downloaded from the smartphone app to 
obtain information regarding homework compliance and estimates of HRVB accuracy; participants 
with low compliance (<75%) will be asked a structured series of questions by their clinician to help 
determine what is promoting or obstructing adherence. 
2.3 Resources Available
Study risks are minimal and may include an increase in distress as a result of topics discussed during 
SCT; however, the methodologies employed have been utilized in many labs and clinical settings with 
hundreds of participants suffering from a range of psychopathology and approved by as many IRBs. 
Participants may also experience temporary discomfort from removal of in-person physiological 
monitoring equipment; abrasions should not be more distressing than removal of band aids.
2.4 Research Sites
Research will take place in the Principal Investigator’s lab space at One Spring Street in downtown New 
Brunswick, the 5th floor of Tillett Hall located on the Livingston Campus in Piscataway, as well as 
remotely. Facilities include materials necessary for data collection (e.g., physiological monitoring 
equipment, laboratory space, sub-zero freezer), and materials and devices needed for remote 
administration of the study will be provided to participants.
3.0 Multi-Center Research
4.0 Subject Considerations
4.1 Subject Selection and Enrollment Considerations 
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A.
Method to Identify Potential Subjects
Study advertisements will be posted in the greater New Brunswick area and Central New Jersey 
through online and community advertisements. Online advertisements via BuildClinical, a digital 
marketing platform, will be posted via social media platforms and will target potential participants 
based on demographic criteria including age and gender. We will utilize online recruitment 
programs to optimize our social media presence as well as expand our recruitment to a wider 
radius. We will also contact and partner with health-related clinics and institutes in the area to 
recruit from their patient population. Additionally, we will also attend and host information 
sessions at events in the New Brunswick community.
B.
Recruitment Details
We will consent up to 50 participants from the greater Rutgers, New Brunswick, NJ area with a 
target of n = 30 who are enrolled in treatment, i.e., meet inclusion/exclusion criteria and who 
complete at least their first intervention session. Participants will be 50% female. We anticipate 
that our sample will reflect the race/ethnicity of the greater New Brunswick, NJ area; however, 
due to the small sample size, it is unlikely that our sample will adequately represent the 
racial/ethnic diversity of the New Brunswick, NJ area, and we will not recruit/enroll participants 
with this intent (i.e., 46.4% Caucasian/non-Hispanic, 23% Asian, 19% Hispanic/Caucasian, 11% 
African-American/non-Hispanic, 0.6 American Indian) (Centers for Disease Control and 
Prevention, 2014)). Participants will be recruited through March 2023 via posters, leaflets, 
mailings, online advertisements, community outreach (i.e., meetings with local organizations and 
treatment providers who work with cigarette smokers), and listservs.  
C.
Subject Screening
Upon initial contact with the lab, participants will be provided with a detailed description of the 
study and after providing verbal consent, will undergo a structured clinical phone screen to 
ensure they are likely to meet study inclusion and exclusion criteria. The phone screen includes 
sensitive questions related to physical and mental health that are necessary to ensure 
participants scheduled are eligible to participate in the study. This protects our resources, as well 
as those of the participant. In accord with lab procedures, we do not store identifying information 
and phone screen responses that may include PHI together. Instead, potential participant 
information including name, contact information, date of screening, and status (e.g., eligible, 
ineligible, scheduled), is stored on a password-protected file on the lab desktop. As an additional 
safeguard, we do not store this information on a network server; it is only accessible via one 
designated computer. Screening data will be stored by 3-digit arbitrary study ID number in a 
separate password-protected file. 

Inclusion Criteria
Inclusion criteria include the following: (1) age 21-50, (2) smoking ≥ 5 cigarettes, daily, for at 
least two years, (3) expired carbon monoxide analysis of breath sample ≥8 ppm (4) a score of 
>5 on the Readiness to Quit Ladder (desire to quit smoking within the next 6 months) (5) 
ability to read and speak English fluently, and (6) computer and smartphone proficient. 

Exclusion Criteria
Exclusion criteria include the following: (1) use of other tobacco or nicotine products for 
recreation or to aid in cessation or use of medication to aid in smoking cessation or currently 
receiving counseling for smoking cessation, (2) endorsement of current or past psychotic or 
manic symptoms indicative of bipolar spectrum or schizophrenia spectrum disorders and/or 
current suicidal or homicidal ideation, (3) inability to provide written informed consent; (4) plan 
to move from the New Brunswick, NJ area within the next 6 months, (5) inability to provide 
written informed consent, (6) current evidence of another substance use disorder (≥ 2 DSM-5 
symptoms, (7) severe visual or hearing impairments, (8) self-reported medical condition or 
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medication use that may be contraindicated for participation in a HRVB or confound autonomic 
parameters: (8a) Being overweight or obese (i.e., body mass index > 35); (8b) Severe asthma 
or breathing problems (e.g., chronic obstructive pulmonary disease, emphysema, bronchitis); 
(8c) currently pregnant or lactating or plans to become pregnant in the next 4 months; (8d) 
Autoimmune disorder (e.g., multiple sclerosis; under or overactive thyroid); (8e) 
Neurodegenerative disorder (e.g., Alzheimer’s disease, Parkinson’s disease); (8f) Current use 
of a psychotropic medication or use of other medication that may affect the cardiovascular 
system (e.g., mood stabilizers, anti-psychotics, MAOIs, tricyclics, beta blockers, 
benzodiazepines; patients taking SSRIs or SNRIs will be enrolled if on a stable regimen for at 
least 6 weeks); (8g) History of heart murmur or arrhythmia; (8h) Pacemaker or other implanted 
cardiac devices;  (8i) Heart disease; or (8j) Abnormal heart or respiratory parameters including 
respiration rate > 20 breaths per minute, extra systoles, or hypertension (e.g., BP reading ≥ 
140/90; this may be determined following baseline assessment. Importantly, the presence of 
any of these exclusion factors, if unknown to the participant would not put them at any risk if 
they participated in the study, it would simply make the CV data more difficult (if not impossible) 
to process and interpret, and (9) self-reported medical issues of potential concern to nicotine 
patch users (i.e., unstable angina pectoris, myocardial infarction, or significant cardiac 
arrhythmia (including atrial fibrillation) in the past 90 days.
4.2 Secondary Subjects
N/A
4.3 Number of Subjects
A. Total Number of Subjects
Up to 50 participants will be consented with a target enrollment of n = 30 who will receive a minimal 
dose of treatment (i.e., at least one intervention session)
B. Total Number of Subjects If Multicenter Study
N/A
C. Feasibility
We have chosen to include participants ages 21-50. Although limited, this allows us to capture a large 
group of current daily smokers, with recent research indicating greatest declines in smoking 
prevalence in those ages 18-24 (Centers for Disease Control and Prevention, 2012). This also helps 
ensure participants have smoked regularly for several years. Research has found that autonomic 
parameters, including heart rate variability, (Berntson et al., 1997) blood pressure, (Cugini et al., 
2003) and the baroreflex, (C. M. Brown, Hecht, Weih, Neundörfer, & Hilz, 2003) are affected by age, 
with significant decreases occurring in middle age. Therefore, inclusion of individuals older than 50 
in this pilot study may confound treatment effects or interpretation of physiological parameters of 
interest. We have chosen to enroll smokers who smoke at least 5 cigarettes daily. We will exclude 
non-daily smokers. This will help in both feasibility as well as generalizability with recent research 
indicating that the proportion of heavy smokers (> 30/day) has declined to 9.1% from 12.5% between 
2010 and 2011, whereas the percent who smoke between 1-9/day has increased to 22%, in the same 
time frame (Centers for Disease Control and Prevention, 2012). This is consistent with other reports 
indicating that smokers are smoking less per day, and that other indicators such as daily smoking 
and time to first cigarette may be better indicators of cigarette dependence (Baker et al., 2007). 
Based on the preliminary feasibility findings from Phase 1A of this trial, a treatment protocol modified 
for predominantly remote instruction (as listed here) may yield several feasibility gains. Specifically, 
the reduced number of in-person study visits will mitigate participant burden (i.e., reduced time 
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traveling, greater flexibility in scheduling sessions, etc.). Teletherapy also allows participants to learn 
and practice their assigned breathing interventions in their daily environments potentially increasing 
the generalizability of the breathing exercises into their daily lives.  The use of a portable and user 
friendly device that is able to connect to a participant’s smartphone may also allow for ease of 
continued use of the intervention.  
4.4 Consent Procedures
A. Consent Process

Location of Consent Process
Verbal consent will be obtained for the initial phone screen. The PI or RA will first explain the 
purpose of the phone screen and limits of confidentiality and provide an overview of the study. 
If potential participants remain interested, they must verbally agree to phone screen 
completion. 
During the initial virtual meeting study personnel will verbally go over the consent form in a 
private room.

Ongoing Consent
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. Details regarding participants who 
withdraw from the study will be discussed at data safety management meetings with study 
personnel that will occur every three months following initiation of recruitment to determine 
adverse event reporting, which will be detailed in all continuing review procedures (see 
attached DSMP for futher details).

Individual Roles for Researchers Involved in Consent
PI supervised/trained graduate students and research assistants will complete all aspects of 
the consent procedures.

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 regardless of their ability 
to make a cessation attempt, they will receive full compensation, 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
In addition to providing written informed consent, participants must verbally indicate that they 
understand the study procedures and that they have no further questions.
B.
Waiver or Alteration of Consent Process 

Waiver or Alteration Details
N/A

Destruction of Identifiers
N/A

Use of Deception/Concealment
N/A
a.
Minimal Risk Justification
N/A
b.
Alternatives
N/A
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c.
Subject Debriefing
N/A
C.
Documentation of Consent

Documenting Consent
The PI or supervised/trained study personnel will complete all aspects of the consent 
procedures. Verbal consent will be obtained for the initial phone screen. The PI or study 
personnel will explain the study procedure and read the verbal consent form. After the 
subject’s questions are answered, verbal consent will be acquired from the subject. Signed 
and verbal consent will be used for study participation, in-person, during Week 0.
During the in-person consent process during Week 0, study personnel will verbally review the 
consent form and explain what they have read, including the procedure, time commitment, 
payment, risks/benefits, and option to discontinue at any time without penalty, to check for 
understanding. Participants will also be provided with their own copy with PI contact 
information and Rutgers IRB contact information highlighted.
The informed consent will be provided only in English since the exclusion criteria for the 
sample include inability to provide written informed consent or non-English speaking

Waiver of Documentation Of Consent (i.e., will not obtain subject’s signature)
N/A
4.5 Special Consent/Populations
A.
Minors-Subjects Who Are Not Yet Adults 

Parental Permission
N/A

Non-Parental Permission
N/A

Assent Process
N/A

Documentation of Assent
N/A

Reaching Age of Majority During Study
N/A
B.
Wards of the State
N/A

Research Outside of NJ Involving Minors
N/A
C.
Non-English-Speaking Subjects
N/A

Process for Non-English-Speaking Subjects
N/A

Short Form Consent for Non-English Speakers
N/A
D.
Adults Unable to Consent / Decisionally Impaired Adults
N/A

NJ Law-Assessment of Regaining the Capacity to Consent
N/A

Capacity to Consent
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N/A
a.
NJ Law-Selecting A Witness 
N/A
b.
Removing a Subject
Described research staff will work to directly address any concerns participants raise, 
resulting in their wish to discontinue, while also ensuring participants maintain autonomy 
in their decision-making and avoiding coercion (e.g., overcoming schedule conflicts, or 
completing assessments only). If participants decide that they would like to completely 
withdraw participation, they will not be further contacted. As indicated above, the PI will 
discuss participant withdrawal with key study personnel to make a determination 
regarding communicating when and how to communicate information to the IRB or 
funding agency (NIDA).
4.6 Economic Burden and/or Compensation for Subjects
6.
Expenses 
Participants may incur costs of transportation to arrive at the study site, however, participants     
will have the option to travel to the study site via prepaid Uber, Lyft, or taxi.
B.
Compensation/Incentives
Participants will receive up to $755 in total study compensation. This includes $10 per session for 
attendance, $35 for the baseline and 1-month follow-up, $50 for their 3-month follow-up 
appointment, $50 bonus for attending 6 out of the 7 sessions (see Table 1). Additionally, subjects 
will be paid up to $105 each week for at-home breathing practice from weeks 2-6. Participants will 
earn $5 for a single 5-minute practice, $10 for 2 practices, or $15 for 3-4 practices resulting in a 
total of 20 minutes. Participants will only be compensated for a total of 20 minutes of practice.
C.
Compensation Documentation
A signature of participants will be obtained upon the completion of the compensation.
 
4.7 Risks of Harm/Potential for Benefits to Subjects
A.
Description of Risks of Harm to Subjects

Reasonably Foreseeable Risks of Harm

(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, Dr. Leyro has 
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) HRVB: There are some minimal risks associated with the administration of the 
proposed breathing intervention.  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. 
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
(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 at in person sessions. 
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. Study personnel will train participants in the lab and 
during remote sessions on proper placement and removal of the Inner Balance ear clip 
sensor.

(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 the PI has 
never experienced this in her prior research.  

(5) Nicotine Replacement Therapy: The transdermal nicotine patch is available over-the-
counter, has been widely used, and its risks are minimal. Possible adverse side effects of 
the nicotine patch include abnormal redness of the skin, itching, headache, insomnia, 
diarrhea, indigestion, and nervousness. We minimize risks by screening patients for 
contraindications of nicotine patch use and requiring physician concurrence. In addition, 
participants will be queried regarding craving and side effects to ensure adequate dosing 
and to reduce adverse effects. Participants who are started at 14mg will be moved up to 
21mg if they report strong cravings, whereas those started at 21mg will be stepped down 
to 14 if they report the nicotine to be uncomfortably stimulating.

(6) Breach of Confidentiality: There is a risk that confidential information about a 
participant may be revealed. Although all technology that is incorporated in the study is 
encrypted and HIPAA compliant, reliance on teletherapy introduces risks such as: 
participants not having access to a confidential and isolated location in which to conduct 
teletherapy sessions and potential identifiable information collected in conjunction with 
using data from the Inner Balance and iCOquit ® Smokerlyzer devices. This could 
conceivably result in discriminatory action against participants by insurers, employers, or 
other groups. However, as an additional layer of protection, a Certificate of Confidentiality 
has been automatically awarded by NIH.

Risk of Harm from an Intervention on a Subject with an Existing Condition
N/A

Other Foreseeable Risks of Harm
Our research team employs standard procedures to ensure confidential information about 
study participation is not disclosed. All data are linked to an arbitrary 3-digit 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 
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and never reported at the level of individual participants. In addition, all participants will be 
explicitly instructed to not modify any iCOQuit, Inner Balance, smartphone, and tablet device 
and application settings or include any identifiable information within these devices and 
applications (See Section E. Minimizing Risks of Harm for additional detail). 

Observation and Sensitive Information
N/A
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
Study risks are minimal and include a small, temporary increase in distress as a result of the 
assessments; however, the methodologies employed have been utilized in many labs and clinical 
settings with hundreds of participants suffering from a range of psychopathology, and approved 
by as many IRBs.
E.
Minimizing Risks of Harm
Participants who indicate psychological distress during participation will be provided with several 
strategies to reduce distress as needed, including, distraction and deep breathing. Staff will conduct 
a thorough risk assessment with participants who report suicidal ideation or intent.
Any participants who report suicidal ideation or intent will be provided with information and phone 
numbers for three local options for mental health care: Rutgers University Behavioral Health Care 
(800-969-5300), Rutgers Health Psychiatry/Psychology Clinic (732-235-7647), and the Rutgers 
Psychological Clinic in (848-445-6111). In the unlikely event that a participant reports an 
imminent intent to harm themselves, we will contact Acute Psychiatric Services (855-515-5700).

Certificate of Confidentiality
Participants will additionally be protected via a Certificate of Confidentiality issued by the 
Department of Health and Human Services. The Certificate will protect the investigators from 
being forced to release research data that contains identifiable information about participants, 
even under a court order or subpoena. The certificate does not protect the investigators from 
being compelled to make disclosures that: (1) have been consented to in writing by the 
participants or the participant’s legally authorized representative, (2) are required by the 
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 201 et seq.) or regulations issued under 
that Act, or (3) have been requested from a research project funded by NIH or DHHS by 
authorized representatives of those agencies for the purpose of audit or program review. The 
Certificate will protect study personnel located at Rutgers University as well as consultants 
affiliated with the proposed project from disclosing information. The Certificate will additionally 
protect the privacy of participants by withholding their names and other identifying 
characteristics from all persons not connected with the conduct of that research.

Provisions to Protect Confidentiality on Study Devices
All participants will be explicitly instructed to not modify or include any identifiable information 
within the iCOQuit, Inner Balance, smartphone, and tablet device settings. Upon return, a lab 
personnel member will connect all used iCOQuit and Inner Balance devices to a lab 
smartphone to confirm that no identifiable information is present upon device retrieval and will 
restore all default settings before the devices are provided to a new participant. For lent 
smartphones and tablets, all identifiable information will be cleared by lab personnel upon 
device retrieval and will be re-checked again before being given to a new participant. Our lab 
will also implement a used/clean technology device clearing system. Specifically, returned 
technology (i.e., iCOQuit, Inner Balance, Smartphone, or Tablet) will be placed in the “used” 
bucket. Once all protection provisions have been employed, the device will then be placed in 
the “clean” bucket. This system will increase ease of redistributing reusable tech devices, 
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identifying those that need to be wiped, and ensureg that redistributed devices are free of 
PHI.  

Provisions to Protect the Privacy Interests of Subjects
Participants will be asked to engage with trained research staff throughout the course of the 
study. However, if participants indicate a desire not to work with a particular staff member, we 
will oblige. In addition, potential participants will not interact with any member of the study 
team that they have a personal or professional relationship with.

Provisions to Protect from Exposure to Contaminants
All used iCOQuit, Inner Balance, smartphone, and tablet devices will be thoroughly cleaned 
with a sanitization wipe upon device retrieval before being given to a new participant to 
reduce the spread of person-to-person contaminants.
F.
Potential Benefits to Subjects
The SCT treatment including the NRT patch is associated with improved smoking cessation 
outcomes, which may have a long-term positive impact on health and psychological well-being. In 
addition, though this study is exploratory in nature and benefits of HRVB have not yet been assessed 
in daily smokers, we are hopeful that participants receiving HRVB will experience additional 
reductions in anxiety and depressive symptoms, and improved physiological health as determined by 
indices of autonomic balance. 
5.0 Special Considerations
5.1 Health Insurance Portability and Accountability Act (HIPAA)
N/A
6.3 Family Educational Rights and Privacy Act (FERPA)
N/A
5.3 Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations)
N/A
A.
Special Populations
B.
N/A
5.4 General Data Protection Regulation (GDPR)
N/A
5.5 NJ Access to Medical Research Act (Surrogate Consent)
N/A
6.4 Data Management Plan
6.5 Data Analysis
Primary analyses will use descriptive statistics to assess feasibility and acceptability of HRVB. Ratings 
of perceived effectiveness, appropriateness, satisfaction, and ease of intervention are made on a 5-
point Liker-type scale ranging from 0=completely disagree to 4=completely agree. Descriptive statistics 
will also be used to assess participant attendance, adherence, indexed by time spent using the 
intervention. Instances of technological limitations will be indexed both by count as well as qualitative 
descriptors (e.g., inner balance device failure to pick up recording; Bluetooth connection errors, etc.)
Secondary analyses for Aim 2.a: Changes in smoking behavior will include descriptive statistics used 
to report total number and percent of participants reporting abstinence on their quit day using the 
intent-to-treat sample as well as those who remain in treatment. Sustained smoking cessation will be 
assessed descriptively using point prevalence abstinence defined by self-reported abstinence verified 
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by both carbon monoxide analysis of breath sample and saliva cotinine. Paired sample t-tests will be 
used to assess changes in smoking rate within participants from baseline to quit day, two-week, one-
month, and three-month follow-up, as a proxy for harm reduction. Secondary analyses for Aim 2.b: 
Changes in emotion distress will include paired sample t-tests used to assess changes in emotional 
distress, including depression, anxiety and stress, within participants, from baseline to two-week, one-
month, and three-month follow-up. To explore whether the intervention may be particularly beneficial 
for smokers with elevated emotional distress, we will examine correlations between baseline 
emotional distress ratings and key outcomes, including feasibility and acceptability ratings, changes 
in smoking behavior, and emotional distress.
6.6 Data Security
The link between participants and their study ID will be stored in a password-protected file, located 
within a password-protected database on an encrypted computer. Only select trained laboratory 
personnel will have access to the file, which will be kept separate from deidentified data. 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 offices in the PI research space at One Spring 
Street or Tillett Hall. All research personnel will complete CITI Human Subjects Research training and 
pass the CITI quizzes. 
6.7 Data and Safety Monitoring
Dr. Leyro has developed a detailed data safety and monitoring plan (see attached DSMP file) that has 
been reviewed and approved by the project’s funding agency (NIH/NIDA). 
A.
Data/Safety Monitoring Plan
Please see DSMP
B.
Data/Safety Monitoring Board Details
Please see DSMP. Although this is study qualifies as a clinical trial, no DSMB is required. 
6.4 Reporting Results
A.
Individual Subjects’ Results 
Individual and aggregate study results will not be shared with subjects. However, participants will be notified 
via informed consent that this trial will be included on clinicaltrials.gov, in compliance with NIH NOT-
OD-16-149. Clinicaltrials.gov provides the public with data regarding clinical trials completion and 
outcomes.
B.
Aggregate Results
N/A 
C.
Professional Reporting
It will be made clear to participants that if information from this study is published or presented at 
scientific meetings, their name and other personal information will not be used.
D.
Clinical Trials Registration, Results Reporting and Consent Posting
The funding proposal is a Phase I/II clinical trial and is thus subject to the NIH Policy on 
Dissemination of NIH funded Clinical Trial Information. Upon receipt of award, this study will be 
registered at ClinicalTrials.gov by the study PI - i.e., Teresa Leyro, Ph.D., the Responsible Party. T. 
Leyro (PI) will additionally be responsible for ensuring that results from this study are submitted to 
ClinicalTrials.gov as outlined by the NIH policy, effective January 18, 2017 (NOT-OD-16-149), and 
according to the specified timeline. In accord with the new NIH policy, Rutgers, The State University 
of New Jersey has an internal policy in place and provides investigators with instructions on how to 
register and report results, to ensure that clinical trials are registered and results are reported in 
compliance with NOT-OD-16-149.
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Detailed Dissemination Plan:
1.
Registration: Our trial will be registered no later than 21 days after enrollment of our first 
participant. Registration information will include a study description, including the condition to 
be treated (i.e., tobacco smoking), the intervention/treatment, and study phase. The study 
design description will include study type, estimated enrollment, allocation, intervention model 
and description, primary purpose, official title, start date and estimated completion date. We 
will additionally include study aims and corresponding intervention/treatment, and primary 
and secondary outcome measures. Finally, detailed eligibility criteria (i.e., 
inclusion/exclusion), and contacts and locations description of the study aims, 
approach/protocol, statistical analysis plan, recruitment information, location, and sponsor 
information will be provided. 
2.
Consent form language: Our consent form will include language notifying participants that 
information on the clinical trial, including a description and results, will be posted at 
ClinicalTrials.gov.
Results information: In accord with this policy, we will ensure that results are reported at 
ClinicalTrials.gov within 12 months of the primary completion date – i.e., the date that the 
final subject follow-up, or final, data collection point. Results to be reported by the indicated 
policy deadline will include participant flow (e.g., recruitment details), demographic and 
baseline characteristics (e.g., race/ethnicity, sex/gender, age, cigarettes smoked daily), key 
outcome measures and analyses, serious and other adverse events, and limitations and 
caveats.
6.5 Secondary Use of the Data   
N/A
7.0 Research Repositories – Specimens and/or Data
N/A
8.0 Approvals/Authorizations
N/A
9.0 Bibliography
Abrams, K., Zvolensky, M., Dorman, L., Gonzalez, A., & Mayer, M. (2011). Development and Validation of 
the Smoking Abstinence Expectancies Questionnaire. Nicotine & Tobacco Research, 13(12), 
1296–1304. https://doi.org/10.1093/ntr/ntr184 
Adams, C. E., Baillie, L. E., & Copeland, A. L. (2011). The smoking-related weight and eating episodes 
test (SWEET): Development and preliminary validation. Nicotine & Tobacco Research, 13(11), 1123-
1131.Adler, N. E., Epel, E. S., Castellazzo, G., & Ickovics, J. R. (2000). Relationship of subjective and 
objective social status with psychological and physiological functioning: Preliminary data in 
healthy, White women. Health Psychology, 19(6), 586–592.
Ari, H., Celiloğlu, N., Ari, S., Coşar, S., Doganay, K., & Bozat, T. (2011). The effect of varenicline on heart 
rate variability in healthy smokers and nonsmokers. Autonomic Neuroscience, 164(1), 82-86. 
Ahorsu, D. K., Lin, C. Y., Imani, V., Saffari, M., Griffiths, M. D., & Pakpour, A. H. (2020). The Fear of 
COVID-19 Scale: Development and Initial Validation. International journal of mental health and 
addiction, 1–9. Advance online publication. https://doi.org/10.1007/s11469-020-00270-8
Ashare R, Sinha R, Lampert R, et al. Blunted vagal reactivity predicts stress-precipitated tobacco 
smoking. Psychopharmacology. 2012;220(2):259-268. PMID: 21938416
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Baker, T. B., Piper, M. E., McCarthy, D. E., Bolt, D. M., Smith, S. S., Kim, S.-Y., . . . Hatsukami, D. (2007). 
Time to first cigarette in the morning as an index of ability to quit smoking: implications for 
nicotine dependence. Nicotine & Tobacco Research, 9(Suppl 4), S555-S570. 
Baker TB, Piper ME, McCarthy DE, Majeskie MR, Fiore MC. Addiction motivation reformulated: An 
affective processing model of negative reinforcement. Psychol Rev. 2004;111(1):33-51. PMID: 
14756584
Barkley, R. A. (2011). Barkley deficits in executive functioning scale (BDEFS). New York, NY: Guilford 
Press. 
Benowitz, N. L., Bernert, J. T., Caraballo, R. S., Holiday, D. B., & Wang, J. (2009). Optimal serum cotinine 
levels for distinguishing cigarette smokers and nonsmokers within different racial/ethnic groups in 
the United States between 1999 and 2004. American Journal of Epidemiology, 169(2), 236-248. 
Bernardi, L., Wdowczyk-Szulc, J., Valenti, C., Castoldi, S., Passino, C., Spadacini, G., & Sleight, P. 
(2000). Effects of controlled breathing, mental activity and mental stress with or without 
verbalization on heart rate variability. Journal of the American College of Cardiology, 35(6), 1462-
1469. 
Berntson, G. G., Bigger, J. T., Eckberg, D. L., Grossman, P., Kaufmann, P. G., Malik, M., . . . 
VanderMolen, M. W. (1997). Heart rate variability: Origins, methods, and interpretive caveats. 
Psychophysiology, 34, 623-648. 
Biener L, Abrams DB. The contemplation ladder: validation of ameasure of readiness to consider smoking 
cessation. Health Psychol. 1991;10(5):360-365.
Brown, C. M., Hecht, M. J., Weih, A., Neundörfer, B., & Hilz, M. J. (2003). Effects of age on the cardiac 
and vascular limbs of the arterial baroreflex. European Journal of Clinical Investigation, 33(1), 10-
16. 
Brown, R. A., Lejuez, C. W., Kahler, C. W., & Strong, D. R. (2002). Distress tolerance and duration of past 
smoking cessation attempts. Journal of Abnormal Psychology, 111(1), 180-185. doi: 
10.1037//0021-843X.111.1.180
Brown RA, Reed KMP, Bloom EL, et al. Development and preliminary randomized controlled trial of a 
distress tolerance treatment for smokers with a history of early lapse. Nicotine Tob Res. 
2013;15(12):2005-2015. PMID: 23884317
Bryant, J., Bonevski, B., Paul, C., McElduff, P., & Attia, J. (2011). A systematic review and meta‐analysis 
of the effectiveness of behavioural smoking cessation interventions in selected disadvantaged 
groups. Addiction, 106(9), 1568-1585. 
Buysse, D. J., Reynolds III, C. F., Monk, T. H., Berman, S. R., & Kupfer, D. J. (1989). The Pittsburgh 
Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry 
research, 28(2), 193-213.
Cappelleri, J. C., Bushmakin, A. G., Baker, C. L., Merikle, E., Olufade, A. O., & Gilbert, D. G. (2005).
Revealing the multidimensional framework of the Minnesota nicotine withdrawal scale. Current 
medical research and opinion, 21(5), 749-760.
Cavanagh, P., & Alvarez, G. A. (2005). Tracking multiple targets with multifocal attention. Trends in 
cognitive sciences, 9(7), 349-354.
Centers for Disease Control and Prevention. (2012). Current cigarette smoking among adults-United 
States, 2011. MMWR: Morbidity and Mortality Weekly Report, 61(44), 889. 
Centers for Disease Control and Prevention. (2014). Current cigarette smoking among adults—United 
States, 2005–2013. MMWR: Morbidity and Mortality Weekly Report, 63(47), 1108-1112. 
Cepeda-Benito, A., Reynoso, J. T., & Erath, S. (2004). Meta-analysis of the efficacy of nicotine 
replacement therapy for smoking cessation: differences between men and women. Journal of 
Consulting and Clinical Psychology, 72(4), 712-722. doi: 10.1037/0022-006X.72.4.712
Cohen, S., & Williamson, G. (1988). Perceived stress in a probability sample of the United States. In S. 
Spacapan & S. Oskamp (Eds.), The social psychology of health: Claremont Symposium on 
applied social psychology. Newbury Park, CA: Sage. 
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Protocol Title: Open Trial of HRVB-SCT
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Cocores, J. (1993). Nicotine dependence: Diagnosis and treatment. Psychiatric Clinics of North America, 
16(1), 49-60. 
Cox, L. S., Tiffany, S. T., & Christen, A. G. (2001). Evaluation of the brief questionnaire of smoking urges 
(QSU-brief) in laboratory and clinical settings. Nicotine & Tobacco Research, 3(1), 7-16. 
Crane NA, Gorka SM, Giedgowd GE, et al. Adolescent’s respiratory sinus arrhythmia is associated with 
smoking rate five years later. Biol Psychol. 2016;118:107-113. PMID: 27235685
Cugini, P., Ferrari, P., De Rosa, R., Caliumi, C., Delfini, E., Colotto, M., . . . Letizia, C. (2003). Severity of 
human hypertension in relation to the age in which high blood pressure makes its presumptive 
appearance. La Clinica Terapeutica, 154(1), 21-26. 
Cyders, M. A., Smith, G. T., Spillane, N. S., Fischer, S., Annus, A. M., & Peterson, C. (2007). Integration 
of impulsivity and positive mood to predict risky behavior: development and validation of a 
measure of positive urgency. Psychological assessment, 19(1), 107.
Devilly, G. J., & Borkovec, T. D. (2000). Psychometric properties of the credibility/expectancy 
questionnaire. J Behav Ther Exp Psy, 31(2), 73-86. 
Dinas, P. C., Koutedakis, Y., & Flouris, A. D. (2013). Effects of active and passive tobacco cigarette 
smoking on heart rate variability. International Journal of Cardiology, 163(2), 109-115. 
Dutra, L., Stathopoulou, G., Basden, S. L., Leyro, T. M., Powers, M. B., & Otto, M. W. (2008). A meta-
analytic review of psychosocial interventions for substance use disorders. American Journal of 
Psychiatry, 165(2), 179-187. 
Fagerström, K. (1978). Measuring degree of physical dependence to tobacco smoking with reference to 
individualization of treatment. Addict Behav, 3(3), 235-241. 
Fagerström, K. (2012). Determinants of tobacco use and renaming the FTND to the Fagerström Test for 
Cigarette Dependence. Nicotine & Tobacco Research, 14(1), 75-78. 
Fairburn, C. G., & Cooper, Z. (2011). Therapist competence, therapy quality, and therapist training. 
Behaviour Research and Therapy, 49(6), 373-378. 
Farris, S. G., DiBello, A. M., Bloom, E. L., & Abrantes, A. M. (2018). A confirmatory factor analysis of the 
smoking and weight eating episodes test (SWEET). International journal of behavioral 
medicine, 25(4), 465-472.
Fiore, M. C., Jaén, C. R., Baker, T. B., Bailey, W. C., Benowitz, N. L., Curry, S. J., . . . Wewers, M. E. 
(2008). Treating tobacco use and dependence: 2008 update. U.S. Department of Health and 
Human Services.
First, M. B., Williams, J. B. W., Karg, R. S., & Spitzer, R. L. (2015). Structured Clinical Interview for DSM-
5 Disorders, Clinical Trials Version (SCID-5-CT). Arlington, VA: American Psychitaric Association.
Gierisch, J. M., Bastian, L. A., Calhoun, P. S., McDuffie, J. R., & Williams, J. W. (2012). Smoking 
cessation interventions for patients with depression: a systematic review and meta-analysis. 
Journal of General Internal Medicine, 27(3), 351-360. 
Gifford EV, Kohlenberg BS, Hayes SC, et al. Does acceptance and relationship focused behavior therapy 
contribute to bupropion outcomes? A randomized controlled trial of functional analytic 
psychotherapy and acceptance and commitment therapy for smoking cessation. Behav Ther. 
2011;42(4):700-715. PMID: 22035998
Gratz KL, Roemer L. Multidimensional assessment of emotion regulation and dysregulation: 
development, factor structure, and initial validation of the difficulties in emotion regulation scale. J 
Psychopathol Behav Assess. 2004;26(1):41-54.
Gregory, H. M. (2010). Smoking Cessation, Varenicline, and Suicide: A Systematic Review. (Master), 
Pacific University.   
Gunnell, D., Irvine, D., & Wise, L. (2009). Varenicline Does Not Appear to Increase Risk of Suicide or 
Depression. JCOM, 16(11), 499-500. 
Hall, S. M., Havassy, B. E., & Wasserman, D. A. (1990). Commitment to abstinence and acute stress in 
relapse to alcohol, opiates, and nicotine. J Consult Clin Psych, 58(2), 175-181. 
Hall, S. M., Havassy, B. E., & Wasserman, D. A. (1991). Effects of commitment to abstinence, positive 
moods, stress, and coping on relapse to cocaine use. Journal of consulting and clinical 
psychology, 59(4), 526.
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Hall, S. M., Humfleet, G. L., Muñoz, R. F., Reus, V. I., Prochaska, J. J., & Robbins, J. A. (2011). Using 
extended cognitive behavioral treatment and medication to treat dependent smokers. American 
Journal of Public Health, 101(12), 2349-2356. 
Hall, S. M., Humfleet, G. L., Muñoz, R. F., Reus, V. I., Robbins, J. A., & Prochaska, J. J. (2009). Extended 
treatment of older cigarette smokers. Addiction, 104(6), 1043-1052. 
Hall, S. M., Humfleet, G. L., Reus, V. I., Muñoz, R. F., & Cullen, J. (2004). Extended nortriptyline and 
psychological treatment for cigarette smoking. American Journal of Psychiatry, 161, 2100-2107. 
Hall, S. M., Muñoz, R. F., & Reus, V. I. (1994). Cognitive-behavioral intervention increases abstinence 
rates for depressive-history smokers. Journal of Consulting and Clinical Psychology, 62(1), 141-
146. 
Hall, S. M., Muñoz, R. F., Reus, V. I., Sees, K. L., Duncan, C., Humfleet, G. L., & Hartz, D. T. (1996). 
Mood management and nicotine gum in smoking treatment: A therapeutic contact and placebo-
controlled study. Journal of Consulting and Clinical Psychology, 64(5), 1003-1009. 
Hall, S. M., Reus, V. I., Muñoz, R. F., Sees, K. L., Humfleet, G., Hartz, D. T., . . . Triffleman, E. (1998). 
Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking. Archives of 
General Psychiatry, 55(8), 683-690. 
Harrington, N. (2005) The Frustration Discomfort Scale: Development and psychometric properties. 
Clinical Psychology & Psychotherapy, 12,374-387. Doi: 10.1002/cpp.465
Harte, C. B., Liverant, G. I., Sloan, D. M., Kamholz, B. W., Rosebrock, L. E., Fava, M., & Kaplan, G. B. 
(2013). Association between smoking and heart rate variability among individuals with 
depression. Annals of Behavioral Medicine, 46(1), 73-80. 
Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., & Fagerstrom, K.-O. (1991). The Fagerstrom Test for 
Nicotine Dependence: A revision of the Fagerstrom Tolerance Questionnaire. Brit J Addict, 86(9), 
1119-1127. 
Hendricks, P. S., Wood, S. B., Baker, M. R., Delucchi, K. L., & Hall, S. M. (2011). The Smoking 
Abstinence Questionnaire: Measurement of smokers’ abstinence-related expectancies. 
Addiction.106, 716–728. doi: 10.1111/j.1360-0443.2010.03338.x
Henry, B. L., Minassian, A., Paulus, M. P., Geyer, M. A., & Perry, W. (2010). Heart rate variability in 
bipolar mania and schizophrenia. Journal of Psychiatric Research, 44(3), 168-176. 
Henry, J. D., & Crawford, J. R. (2005). The short‐form version of the Depression Anxiety Stress Scales 
(DASS‐21): Construct validity and normative data in a large non‐clinical sample. British Journal of 
Clinical Psychology, 44(2), 227-239. 
Hitsman, B., Borrelli, B., McChargue, D. E., Spring, B., & Niaura, R. (2003). History of depression and 
smoking cessation outcome: A meta-analysis. Journal of Consulting and Clinical Psychology, 
71(4), 657-663. 
Hudson, N. L., & Mannino, D. M. (2010). Tobacco use: a chronic illness? Journal of Community Health, 
35(5), 549-553. 
Hughes, J. R., & Hatsukami, D. ( 1986). Signs and symptoms of tobacco withdrawal. Arch Gen Psychiat, 
43, 289-294. 
Jaén, C. R., Benowitz, N. L., Curry, S. J., Parsippany, N., Kottke, T. E., Mermelstein, R. J., . . . Wewers, 
M. E. (2008). A clinical practice guideline for treating tobacco use and dependence: 2008 update. 
American Journal of Preventive Medicine, 35(2), 158-176. 
Jain FA, Cook IA, Leuchter AF, et al. Heart rate variability and treatment outcome in major depression: A 
pilot study. Int J Psychophysiol. 2014;93(2):204-210. PMID: 24769434
Jarvis, M. J., Tunstall-Pedoe, H., Feyerabend, C., Vesey, C., & Saloojee, Y. (1987). Comparison of tests 
used to distinguish smokers from nonsmokers. American Journal of Public Health, 77(11), 1435-
1438. 
Kajantie, E., & Phillips, D. I. (2006). The effects of sex and hormonal status on the physiological response 
to acute psychosocial stress. Psychoneuroendocrinology, 31(2), 151-178. 
Kashdan TB, Rottenberg J. Psychological flexibility as a fundamental aspect of health. Clin Psychol Rev. 
2010;30(7):865-878. PMID: 21151705
Kessler, R. C., Adler, L., Ames, M., Demler, O., Faraone, S., Hiripi, E. V. A., ... & Ustun, T. B. (2005). The 
World Health Organization Adult ADHD Self-Report Scale (ASRS): a short screening scale for 
use in the general population. Psychological medicine, 35(2), 245-256.
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Koffarnus, M. N., & Bickel, W. K. (2014). A 5-trial adjusting delay discounting task: Accurate discount 
rates in less than one minute. Experimental and Clinical Psychopharmacology, 22(3), 222-228. 
http://dx.doi.org/10.1037/a0035973
Lawrence D, Mitrou F, Zubrick SR. Smoking and mental illness: results from population surveys in 
Australia and the United States. BMC Public Health. 2009;9(1):285-298. PMID: 19664203
Lee, P. (2014). Heart rate variability using the phone's camera. from 
http://www.marcoaltini.com/blog/heart-rate-variability-using-the-phones-camera
Lehrer, P. M., & Gevirtz, R. (2013). Heart rate variability biofeedback: How and why does it work? 
Frontiers in Psychology, 5, 756-756. 
Lehrer, P. M., Vaschillo, B., Zucker, T., Graves, J., Katsamanis, M., Aviles, M., & Wamboldt, F. (2013). 
Protocol for heart rate variability biofeedback training. Biofeedback, 41(3), 98-109. 
Lehrer PM, Vaschillo E. Heart rate variability biofeedback: A new tool for improving autonomic 
homeostasis and treating emotional and psychosomatic diseases. Japanese Journal of 
Biofeedback Research. 2004;30:7-16. NAID 110003162987 
Lehrer, P. M., Vaschillo, E., & Vaschillo, B. (2000). Resonant frequency biofeedback training to increase 
cardiac variability: Rationale and manual for training. Applied Psychophysiology and Biofeedback, 
25(3), 177-191. 
Lehrer PM, Vaschillo E, Vaschillo B, et al. Heart rate variability biofeedback increases baroreflex gain and 
peak expiratory flow. Psychosom Med. 2003;65(5):796-805. PMID: 14508023
Lehrer, P. M., Vaschillo, E., Vaschillo, B., Lu, S.-E., Eckberg, D. L., Edelberg, R., . . . Tahvanainen, K. U. 
(2003). Heart rate variability biofeedback increases baroreflex gain and peak expiratory flow. 
Psychosomatic Medicine, 65(5), 796-805. 
Leung, J. Y., Barr, A. M., Procyshyn, R. M., Honer, W. G., & Pang, C. C. (2012). Cardiovascular side-
effects of antipsychotic drugs: The role of the autonomic nervous system. Pharmacology & 
Therapeutics, 135(2), 113-122. 
Leventhal AM, Zvolensky MJ. Anxiety, depression, and cigarette smoking: A transdiagnostic vulnerability 
framework to understanding emotion-smoking comorbidity. Psychol Bull. 2015;141(1):176-212. 
PMID: 25365764
Leyro, T. M., Thompson, R., Yang, M.-J., Borges, A., & Mendes, W. B. (2017, April). Conditional Effect of 
Distress Intolerance on Emotional Recovery from Trier Social Stress Task as a Function of Vagal 
Flexibility. Paper presented at the Anxiety and Depression Association of America, San 
Francisco, CA.
Libby DJ, Worhunsky PD, Pilver CE, Brewer JA. Meditation-induced changes in high-frequency heart rate 
variability predict smoking outcomes. Front Hum Neurosci. 2012;6:54. PMID: 22457646
Licht, C. M., De Geus, E. J., Van Dyck, R., & Penninx, B. W. (2009). Association between anxiety 
disorders and heart rate variability in The Netherlands Study of Depression and Anxiety 
(NESDA). Psychosomatic Medicine, 71(5), 508-518. 
MacKillop, J., Murphy, J. G., Ray, L. A., Eisenberg, D. T., Lisman, S. A., Lum, J. K., & Wilson, D. S. 
(2008). Further validation of a cigarette purchase task for assessing the relative reinforcing 
efficacy of nicotine in college smokers. Experimental and Clinical Psychopharmacology, 16(1), 
57.
Macnee CL, Talsma A. Development and testing of the barriers to cessation scale. Nurs Res. 
1995;44(4):214-219.
Marlatt, G. A., Curry, S., & Gordon, J. (1988). A longitudinal analysis of unaided smoking cessation. J 
Consult Clin Psych, 56(5), 715. 
McHugh RK, Otto MW. Domain-general and domain-specific strategies for the assessment of distress 
intolerance. Nicotine Tob Res. 2011;25(4):745-749.
Mohr, D. C., Spring, B., Freedland, K. E., Beckner, V., Arean, P., Hollon, S. D., . . . Kaplan, R. (2009). The 
selection and design of control conditions for randomized controlled trials of psychological 
interventions. Psychotherapy and Psychosomatics, 78(5), 275-284. 
Moodithaya, S., & Avadhany, S. T. (2011). Gender differences in age-related changes in cardiac 
autonomic nervous function. J Aging Res, 2012, 1-7. 
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           9/28/2022
           9/17/2024


Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v9 9/23/22
Page 38 of 41
Moon E, Lee S-H, Kim D-H, Hwang B. Comparative study of heart rate variability in patients with 
schizophrenia, bipolar disorder, post-traumatic stress disorder, or major depressive disorder. Clin 
Psychopharmacol Neurosci. 2013;11(3):137-143. PMID: 24465250
Moore, C. G., Carter, R. E., Nietert, P. J., & Stewart, P. W. (2011). Recommendations for planning pilot 
studies in clinical and translational research. Clinical and Translational Science, 4(5), 332-337. 
Muhtadie, L., Koslov, K., Akinola, M., & Mendes, W. B. (2015). Vagal flexibility: A physiological predictor 
of social sensitivity. Journal of Personality and Social Psychology, 109(1), 106-120. doi: 
10.1037/pspp0000016
Muse, K., & McManus, F. (2013). A systematic review of methods for assessing competence in cognitive–
behavioural therapy. Clinical Psychology Review, 33(3), 484-499. 
National Cancer Institute. (2013). Clear pathways: Winning the fight against tobacco.  Atlanta, GA.: U. S. 
Department of Health and Human Services, National Institute of Health.
Norton, P., & Sears Edwards, K. (2017). Anxiety Sensitivity or Interoceptive Sensitivity. European Journal 
of Psychological Assessment, 33(1), 30–37. https://doi.org/10.1027/1015-5759/a000269 
Park G, Thayer JF. From the heart to the mind: cardiac vagal tone modulates top-down and bottom-up 
visual perception and attention to emotional stimuli. Front Psychol. 2014;5:1-8. PMID: 24817853
Park G, Van Bavel JJ, Vasey MW, Thayer JF. Cardiac vagal tone predicts attentional engagement to and 
disengagement from fearful faces. Emotion. 2013;13(4):645-656. PMID: 23914769
Perkins, K. A., & Scott, J. (2008). Sex differences in long-term smoking cessation rates due to nicotine 
patch. Nicotine & Tobacco Research, 10(7), 1245-1251. 
Piper ME, Cook JW, Schlam TR, Jorenby DE, Baker TB. Anxiety diagnoses in smokers seeking cessation 
treatment: Relations with tobacco dependence, withdrawal, outcome and response to treatment. 
Addiction. 2011;106(2):418-427. PMID: 20973856
Piper, M., Piasecki, T., Federman, E., Bolt, D., Smith, S., Fiore, M., … Sobell, M. (2004). A Multiple 
Motives Approach to Tobacco Dependence: The Wisconsin Inventory of Smoking Dependence 
Motives (WISDM-68). Journal of Consulting and Clinical Psychology, 72(2), 139–154. 
https://doi.org/10.1037/0022-006X.72.2.139.
Pothineni, N. V., Shirazi, L. F., & Mehta, J. L. (In press). Gender differences of autonomic control of the 
cardiovascular system. Current Pharmaceutical Design. 
Preacher KJ. Latent growth curve modeling. Sage; 2008 Jun 27.
Prochaska, J. J., & Hilton, J. F. (2012). Risk of cardiovascular serious adverse events associated with 
varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ, 344, e2856. 
Rose, L., Zask, A., & Burton, L. (2017). Psychometric properties of the Meaning in Life Questionnaire 
(MLQ) in a sample of Australian adolescents. International Journal of Adolescence and 
Youth, 22(1), 68–77. https://doi.org/10.1080/02673843.2015.1124791
Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology. 1990 Jan 1;1(1):43-6.
Rottenberg J, Salomon K, Gross JJ, Gotlib IH. Vagal withdrawal to a sad film predicts subsequent 
recovery from depression. Psychophysiology. 2005;42(3):277-281. PMID: 15943681
Schmidt, N. B., Lerew, D. R., & Jackson, R. J. (1997). The role of anxiety sensitivity in the pathogenesis 
of panic: Prospective evaluation of spontaneous panic attacks during acute stress. Journal of 
Abnormal Psychology, 106, 355–364.
Schuch, J. J., Roest, A. M., Nolen, W. A., Penninx, B. W., & de Jonge, P. (2014). Gender differences in 
major depressive disorder: Results from the Netherlands study of depression and anxiety. Journal 
of Affective Disorders, 156, 156-163. 
Sepkovic, D. W., & Haley, N. J. (1985). Biomedical applications of cotinine quantitation in smoking related 
research. American Journal of Public Health, 75(6), 663-665. 
Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E., Hergueta, T., Baker, R., 
Dunbar, G.C. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and 
validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin 
Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57
Shiffman, S., Waters, A. J., Hickcox, M. (2004) The Nicotine Dependence Syndrome Scale: A 
multidimensional measure of nicotine dependence. Nicotine & Tobacco Research, 6 (2), 327–
348. DOI: 10.1080/1462220042000202481
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           9/17/2024


Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v9 9/23/22
Page 39 of 41
Simons, J. S., & Gaher, R. M. (2005). The Distress Tolerance Scale: Development and validation of a 
self-report measure. Motiv Emotion, 29(2), 83-102. 
Sirota, A. D., Rohsenow, D. J., MacKinnon, S. V., Martin, R. A., Eaton, C. A., Kaplan, G. B., ... & Swift, R. 
M. (2010). Intolerance for Smoking Abstinence Questionnaire: Psychometric properties and 
relationship to tobacco dependence and abstinence. Addictive behaviors, 35(7), 686-693.
Sjoberg, N., & Saint, D. A. (2011). A single 4 mg dose of nicotine decreases heart rate variability in 
healthy nonsmokers: Implications for smoking cessation programs. Nicotine & Tobacco 
Research, 13(5), 369-372. 
Smith, P. H., Bessette, A. J., Weinberger, A. H., Sheffer, C. E., & McKee, S. A. (2016). Sex/gender 
differences in smoking cessation: A review. Preventive Medicine, 92, 135-140. 
Sobell, L. C., Brown, J., Leo, G. I., & Sobell, M. B. (1996). The reliability of the Alcohol Timeline 
Followback when administered by telephone and by computer. Drug Alcohol Depen, 42(1), 49-54. 
Sobell, L. C., & Sobell, M. B. (1992). Timeline follow-back Measuring Alcohol Consumption (pp. 41-72): 
Humana Press.
Sobell, L. C., & Sobell, M. B. (1995). Alcohol timeline followback users’ manual. Toronto, Canada: 
Addiction Research Foundation.
Sood, R., Sood, A., Wolf, S. L., Linquist, B. M., Liu, H., Sloan, J. A., . . . Barton, D. L. (2013). Paced 
breathing compared with usual breathing for hot flashes. Menopause, 20(2), 179-184. 
Stein, P. K., Rottman, J. N., & Kleiger, R. E. (1996). Effect of 21 mg transdermal nicotine patches and 
smoking cessation on heart rate variability. American Journal of Cardiology, 77(9), 701-705. 
Stevens S. Smith, Megan E. Piper, Daniel M. Bolt, Michael C. Fiore, David W. Wetter, Paul M. Cinciripini, 
Timothy B. Baker, Development of the Brief Wisconsin Inventory of Smoking Dependence 
Motives, Nicotine & Tobacco Research, Volume 12, Issue 5, May 2010, Pages 489–
499, https://doi.org/10.1093/ntr/ntq032
Taylor S, Zvolensky MJ, Cox BJ, et al. Robust dimensions of anxiety sensitivity: development and initial 
validation of the Anxiety Sensitivity Index-3. Psychol Assess. 2007;19(2):176-188.
Taylor, S., Landry, C. A., Paluszek, M. M., Fergus, T. A., McKay, D., & Asmundson, G. J. (2020). 
Development and initial validation of the COVID Stress Scales. Journal of Anxiety Disorders, 72, 
102232.
Thayer JF, Åhs F, Fredrikson M, Sollers JJ, Wager TD. A meta-analysis of heart rate variability and 
neuroimaging studies: Implications for heart rate variability as a marker of stress and health. 
Neurosci Biobehav Rev. 2012;36(2):747-756. PMID: 22178086
Thayer JF, Lane RD. A model of neurovisceral integration in emotion regulation and dysregulation. J 
Affect Disord. 2000;61(3):201-216. PMID: 11163422
Thayer, J. F., Yamamoto, S. S., & Brosschot, J. F. (2010). The relationship of autonomic imbalance, heart 
rate variability and cardiovascular disease risk factors. International Journal of Cardiology, 141(2), 
122-131. 
Ustun, B., Adler, L., & Rudin, C. (2017). The World Health Organization AdultAttention-
Deficit/Hyperactivity Disorder Self-report Screening Scale for DSM-5 (vol 74, pg 520, 2017). Jama 
Psychiatry, 74(12), 1279–1279.
University of Wisconsin Population Health Institute. (2013). Adult smoking. 2013 Rankings New Jersey, 
County Health Rankings & Roadmaps. from http://www.countyhealthrankings.org/app/new-
jersey/2013/measure/factors/9/map
Ware, J. E., Kosinski, M., & Keller, S. D. (1996). A 12-item Short-Form Health Survey: Construction of 
scales and preliminary tests of reliability and validity. Med Care, 34, 220-233. 
Wasserman, D. A., Havassy, B. E., & Boles, S. M. (1997). Traumatic events and post-traumatic stress 
disorder in cocaine users entering private treatment. Drug Alcohol Depen, 46(1), 1-8. 
Watson, D., & Clark, L. A. (1999). The PANAS-X: Manual for the positive and negative affect schedule-
expanded form. 
Watson, D., Clark, L. A., & Tellegen, A. (1988). Development and validation of brief measures of positive 
and negative affect: The PANAS scales. Journal of Personality and Social Psychology, 54(6), 
1063-1070. 
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Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v9 9/23/22
Page 40 of 41
Whiteside, S. P., & Lynam, D. R. (2001). The five factor model and impulsivity: Using a structural model of 
personality to understand impulsivity. Personality and individual differences, 30(4), 669-689. 
Williams JM, Steinberg ML, Griffiths KG, Cooperman N. Smokers with behavioral health comorbidity 
should be designated a tobacco use disparity group. Am J Public Health. 2013;103(9):1549-1555. 
PMID: 23865661
Zawertailo L, Voci S, Selby P. Depression status as a predictor of quit success in a real-world 
effectiveness study of nicotine replacement therapy. Psychiatry Res. 2015;226(1):120-127. PMID: 
25618468
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ICF_001.pdf: 
TITLE: Open Trial of Heart Rate Variability Biofeedback for Smoking Cessation 
NCT05224050 
PI: Teresa Leyro, Ph.D. 
Document Date: 01/25/2023 


Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
Page 1 of 12
CONSENT TO TAKE PART IN A RESEARCH STUDY
Title of Study: Open Trial of Breath Training for Smoking Cessation 
Principal Investigator: Teresa M. Leyro, Ph.D.
STUDY SUMMARY: This consent form is part of an informed consent process for a research study, and it will 
provide information that will help you decide whether you want to take part in this study. It is your choice to take 
part or not. 
The purpose of the research is to help smokers quit smoking. If you take part in the research, you will be asked to 
attend smoking cessation counseling, use nicotine replacement therapy, and participate in a breathing 
intervention. Your time in the study will take place over the course of 4 months, including 3 in-lab visits, and 5 
remote sessions. 
Possible harms or burdens of taking part in the study may be side effects from the Nicotine Transdermal Patch, 
discomfort related to quitting smoking, physical discomfort due to our breathing intervention requiring you to 
breath differently than is typical, slight emotional distress when completing questionnaires, interviews, and 
counseling services. Possible benefits of taking part may be access to high-quality, evidence-based smoking 
cessation treatment.
An alternative to taking part in the research study: If you choose not to take part in this study and express interest 
in another cessation program, we will provide you with information regarding other treatment options. Examples 
include a free telephone QuitLine or a local smoking cessation clinic.
The information in this consent form will provide you with more details about the research study and what will be 
asked of you if you choose to take part in it. If you have any questions now or during the study, if you choose to 
take part, you should feel free to ask them and should expect to be given answers you completely understand.  
After your questions have been answered and you wish to take part in the research study, you will be asked to sign 
this consent form. You are not giving up any of your legal rights by agreeing to take part in this research or by 
signing this consent form.
Who is conducting this study?
Teresa M. Leyro, Ph.D. is the Principal Investigator of this research study.  A Principal Investigator has the overall 
responsibility for the conduct of the research. However, there are often other individuals who are part of the 
research team. Other individuals working as co-investigators or study staff may assist or act for the Principal 
Investigator.
Teresa M. Leyro, Ph.D. may be reached at 732-659-4283 or teresa.leyro@rutgers.edu. Study staff can also be 
reached at abusa@psych.rutgers.edu . 
The Principal Investigator or another member of the study team will also be asked to sign this informed consent.  
You will be given a copy of the signed consent form to keep.
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 2 of 12
Sponsor of the Study: National Institute on Drug Abuse (NIDA).
Why is this study being done?
The purpose of this study is to help individuals who smoke cigarettes quit smoking.  The research study will 
develop and test whether the inclusion of a breath training component with standard smoking cessation treatment 
is useful. The research study will also test whether the inclusion of this breath training component is particularly 
helpful for individuals who may struggle with elevated mood and anxiety symptoms in their attempt to quit. First, 
we aim to test whether the intervention is easy and useful to implement. Second, we hope to improve smoking 
cessation outcomes and to reduce mood and anxiety symptoms.  
Cigarette smoking remains the leading cause of preventable death and poses an immense economic and health 
burden, in particular for those affected by comorbid anxiety and mood disorders. Individuals who smoke who also 
suffer from elevated emotional distress tend to smoke at greater rates, report greater cigarette dependence, and 
experience tremendous difficulty quitting. 
Among these individuals, alterations to the autonomic nervous system have been observed, and may make it more 
difficult to cope with cigarette withdrawal and emotional distress. Breathing interventions are one strategy that 
may be used to improve autonomic nervous system functioning, and also improve how well individuals can 
regulate distressing experiences. 
We hope that adding a breath training component to a smoking cessation program will provide smokers who want 
to quit with a cost-effective and efficient tool. We also hope that it will increase the likelihood that individuals who 
smoke are able to achieve prolonged abstinence and will also have a positive impact on emotional symptoms. 
The current researchers have no financial or propriety disclosures relevant to the current project. 
Who may take part in this study and who may not?
You may participate in this study if:
•
You are between the ages of 21 and 50
•
Have been smoking at least five cigarettes daily for the last two years
•
Are proficient in reading and speaking English
•
Are proficient in the use of a computer 
You will not be eligible to participate in this study if:
•
You are currently pregnant or lactating
•
Using other tobacco or nicotine products, including those used to help you quit
•
Currently receiving smoking cessation counseling or taking medication to help you quit
•
Have evidence of experiencing current or past psychotic or manic symptoms
•
Have current suicidal or homicidal thoughts or behaviors 
•
Have a self-reported pending legal issue which may result in incarceration
•
Have plans to leave the greater New Brunswick, NJ area in the next 6 months
•
Have evidence of another current moderate or severe substance use disorder
•
Have severe visual or hearing impairments
•
Have a medical condition
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 3 of 12
•
Are taking a medication that may affect the utility of the breath training component for you or its 
potential benefit for you
Why have I been asked to take part in this study?
We hope that this study will help individuals who smoke cigarettes quit smoking, as well as test and develop a 
breathing based intervention as a treatment adjunct for smoking cessation. 
How long will the study take and how many subjects will take part?
We expect 30 individuals who smoke daily to complete our study. Each participant will meet with the research 
team up to 8 times over the course of 4 months. Following your baseline session, you will receive 7 intervention 
sessions. This includes 2 intervention sessions before your quit date (one of which will be on the same day as the 
baseline session), and additional counseling sessions during weeks 2, 3, 4, 5, and 6. Your final appointment will be 
scheduled to occur 3 months after your quit date.  
What will I be asked to do if I take part in this study?
If you agree to participate in the study, the following procedures will occur:
Screening: Phone Assessments: The phone assessments will last approximately 1 hour. 
You will first speak with Dr. Leyro or another trained staff member over the phone who will go over several 
assessments with you. This will include an initial screening and a diagnostic interview to assess whether or not you 
are eligible for study participation.
•
First, we will complete a phone screen. During this screening, you will be asked questions about your 
current and past medical and psychological history to determine basic eligibility. 
•
Second, you will complete a diagnostic interview. During the interview, you will be asked to provide 
details regarding current and prior thoughts, feelings, and behaviors, and fill in a few surveys, including 
contact information, information about your mood and emotions, and more detailed information on your 
medical history.
•
Then, you’ll be emailed and asked to complete a set of online questionnaires to obtain additional 
information about your current mood, personality characteristics, as well as tobacco use, withdrawal, 
craving, and urge.
If you are found to be eligible for participation in this study, you will be asked to come into the lab to complete 
physiological assessments before being enrolled in our study intervention, which include smoking cessation 
counseling, nicotine replacement therapy, and a breathing intervention.
Baseline: In-Lab Visit 1:  Visit 1 will last approximately 3-4 hours. 
In the lab, you will speak with Dr. Leyro or another trained staff member who will go over additional assessments 
with you. This will include a carbon monoxide analysis of your breath to ensure your smoking status, 
questionnaires to learn more about your physical and mental health as well as your daily smoking patterns and 
health behaviors, a measurement of your height and weight, and physiological measures. 

During the carbon monoxide analysis, you will be asked to blow air into a tube that is attached to a 
machine, which determines the amount of carbon monoxide in your lungs. This is used to determine 
whether you are currently smoking.    
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 4 of 12
•
Next, you will be attached to sensors on your arms, neck, torso, and fingers that will allow us to measure 
your heart rate, cardiac activity, blood pressure, and respiration. There are no known risks associated with 
this assessment. New sterile sensors are used for each participant. While you are attached to the 
equipment, you will be asked to complete a few computerized tasks.
If you are still deemed eligible, you will learn a breathing intervention and how to use a smartphone app to breathe 
at a certain rate. In addition, each participant will receive smoking cessation counseling and nicotine replacement 
therapy patches. 
You will be asked to provide the names and contact information for three individuals who may be contacted if we 
are unable to reach you during your participation in this study. If we are unable to reach you, we will attempt to 
contact these individuals in order to reach you. We may also contact these individuals to learn whether or not you 
are currently smoking. You will be contacted for all assessments, independent of whether you continue treatment, 
and you will be compensated accordingly. 
 
Intervention Overview: In-Lab and Remote: Sessions will last 60-90 minutes. You will work with a separate breath 
training counselor and smoking cessation counselor. You will complete a total of 7 breath training sessions. You 
will also complete a total of 6 smoking cessation sessions. Two breath training and two smoking cessation 
intervention sessions will occur face-to-face in the lab, with the remainder conducted remotely via Zoom. 
During week 1, you will have two breath training and two smoking cessation sessions; the first session will be in the 
lab immediately following your baseline assessments, and the second will be conducted remotely through 
teletherapy. Your quit day will be scheduled for week 2 of treatment. 
You will then have once weekly treatment sessions. Weeks 2, 3, 4, and 5 will also be conducted remotely through 
teletherapy. Week 6 you will come back into the lab for an in-person session. Intervention sessions will include a 
combination of smoking cessation skills and breath training using the Inner Balance device, with the exception of 
week 5 when you will only meet with your breathing therapist. In-lab and remote sessions will also include taking a 
sample of your breath via carbon monoxide analysis to determine your current smoking status and completing a 
few questionnaires about your physical and mental health, as well as your current thoughts, urges, and cravings 
surrounding smoking.  We will video and/or audio record therapy sessions to ensure that counseling is provided as 
intended. An overview of the intervention schedule is provided in Table 1. 
Table 1. Overview of Intervention Schedule
Week
Treatment
Week 1 (Session 1)
In-person Baseline, Smoking Cessation, & Breath Training
Week 1 (Session 2)
Remote Smoking Cessation & Breath Training
Week 2 (Session 3, Quit Day)
Remote Smoking Cessation & Breath Training
Week 3 (Session 4)
Remote Smoking Cessation & Breath Training
Week 4 (Session 5)
Remote Smoking Cessation & Breath Training
Week 5 (Session 6)
Remote Breath Training
Week 6 (Session 7, 1 Month Follow Up)
In-person 1 Month Follow Up, Smoking Cessation, & Breath Training
Week 15 (3 Month Follow Up)
In-person 3 Month Follow Up
In addition, we will provide you with 8 weeks of nicotine replacement therapy patch. At week 1, we will provide 
you with the nicotine replacement therapy (NRT) patch and instructions for use. You will be asked to begin using 
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 5 of 12
the patch on the morning of your quit date. We will provide you with the patch for 8 weeks. Throughout this 
period, we will help you step down, or decrease, the amount of nicotine in the patches you are using. After 8 
weeks of using the NRT patch, we will ask that you refrain from all nicotine use. 
Study staff will go over the details of your treatment schedule prior to your leaving. You will also receive text, 
phone, and email reminders of all study appointments. 
At-home Practice: 
All participants will be asked to complete at-home practice as part of their intervention. This will include planning 
for your quit date, practicing skills that will help you be successful in quitting, and practicing your breath training 
using the Inner Balance app for at least 10 but ideally up to 20 minutes a day.
Follow-up Appointments: 
Your 1-month and 3-month follow-up sessions will include an analysis of your breath to determine whether or not 
you are currently smoking via your self-report and carbon monoxide analysis and a measurement of your height 
and weight. We will also routinely assess your physiology to monitor any changes that occur throughout your quit 
attempt and use of your breathing intervention. You will be attached to sensors on your arms, neck, torso, and 
fingers that will allow us to measure your heart rate, cardiac activity, blood pressure, and respiration. There are no 
known risks associated with this assessment. New sterile sensors are used for each participant. While you are 
attached to the equipment, you will be asked to complete a few computerized tasks. 
If we detect a possible abnormal ECG during our in-person session, we will inform you in the event you might want 
to follow up with a physician. However, please note that our equipment is not medical grade. We will not provide 
the actual ECG or other physiological records because our procedures are not designed for clinical diagnosis.
You will come in for a final follow-up appointment approximately 3 months after your quit date. Your final follow-
up appointment includes all of the above as well as a collecting a sample of your saliva. Saliva collection is a simple, 
painless procedure that takes approximately 3 minutes. This will help us determine your smoking status during 
your 3-month follow up appointment. 
What are the risks of harm or discomforts I might experience if I take part in this study?
Overall, the risks in this study are very minimal and may include the following: 
•
The Nicotine Transdermal Patch (“the patch”) has few side effects and is sold over the counter in the 
United States. Potential side effects of the nicotine patch include dizziness, headache, nausea, vomiting, 
diarrhea, or redness or swelling at the patch site. Individuals who smoke and have serious arrhythmias (a 
disorder of the heart rate (pulse) or heart rhythm, such as beating too fast, too slow, or irregularly) or 
have chest pains due to coronary artery disease should use the patch with caution.
•
Discomfort related to quitting smoking during the study may include increased anxiety, irritability, 
difficulty concentrating, headaches, upset stomach, and tobacco cravings. These symptoms are typical of 
short-term nicotine withdrawal and result from the addictive nature of nicotine. Although symptoms of 
nicotine withdrawal may be uncomfortable, they are not harmful to your health. As someone who 
smokes, you may have already had numerous experiences with these sensations and feelings throughout 
your day-to-day life. In addition, these symptoms will be directly addressed as part of your treatment. 
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 6 of 12
•
You may also experience physical discomfort throughout the study. For example, the breathing 
intervention requires you to breath differently than is typical. Because it may seem unusual, participants 
may occasionally report some discomfort. Also, attachment of electrodes, although passive, may result in 
some discomfort upon removal. However, removal is no more painful than removing an adhesive 
bandage.
•
There is a slight risk of feeling emotional distress and frustration when completing our questionnaires, 
interviews, and counseling sessions; however, this is minimal and can be addressed by Dr. Leyro, who is a 
licensed clinical psychologist, if necessary. You may also refuse to answer any individual questions you are 
asked.
•
You may find the use of study apps frustrating to learn. However, your breathing therapist will train you 
on how to use these apps and check in with you on your experience with the apps during your weekly 
sessions. You can also email or call us if you continue to experience problems with the apps. 
•
Finally, there is a risk that your confidentiality could be violated. To reduce the risk of violating 
confidentiality, several steps will be taken. Only IRB approved members of the research team will have 
access to the data, only IRB approved software and devices will be used, and all teletherapy platforms will 
be HIPPA compliant.  Data will only be accessed when coded, entered, or audited.  All data will be stored 
in locked cabinets within locked rooms.  Based on these procedures, we anticipate that the risk to 
confidentiality is very low. This study has also been granted a Certificate of Confidentiality from the 
National Institutes of Health, the details of which are described below.
•
Participation in this study may pose unknown and unforeseeable risks. 
Are there any benefits to me if I choose to take part in this study?
The benefits of taking part in this study may be access to high-quality, evidence-based smoking cessation 
treatment. In addition, indirect benefit from your participation includes contributing to research on smoking 
cessation and emotional distress. This research may have implications for smoking interventions. However, it is 
possible that you may not receive any direct benefit from taking part in this study.
What are my alternatives if I do not want to take part in this study?
Clinical practice guidelines for smoking cessation recommend getting behavioral support plus at least one of the 
seven FDA approved medications for smoking cessation. If you choose not to take part in this study and express 
interest in another cessation program, we will provide you with information regarding other treatment options. 
Examples include a free telephone QuitLine or a local smoking cessation clinic.
How will I know if new information is learned that may affect whether I am willing to stay in the study? During 
the study, you will be updated about any new information that may affect whether you are willing to continue 
taking part in the study.  If new information is learned that may affect you after the study or your followup is 
completed, you will be contacted.
Will there be any cost to me to take part in this study?
Aside from the time associated with coming to the New Brunswick Campuses of Rutgers University, there are no 
expected costs of participation. You have the option to request a prepaid Uber, Lyft, or taxi to cover travel costs.
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 7 of 12
Will I be paid to take part in this study?
In return for your time and effort required to take part in this study, you will receive up to $755 for participation. 
You will accrue $35 for the completion of baseline assessments (even if ineligible for the remainder of the study), 
$10 for each week of intervention weeks 1, 2, 3, 4, and 5, $35 for week 6, $50 for completion of your 3-month 
follow-up appointment at week 15, and up to $105 weekly compensation for at-home breathing practice using the 
Inner Balance device provided to you. To facilitate your practice, we ask that you practice using a smartphone and 
provide us with several brief ratings of how you feel before and after each practice session. You will additionally 
receive a $50 bonus for making it to 6 out of 7 treatment session and returning all study-provided devices (e.g., the 
Inner Balance device, the iCOquit CO monitor, a smartphone or tablet if you borrowed one for the study, etc). If 
you withdraw from the study, we ask that you return any study-provided devices (e.g., smartphone or tablet), and 
then we will provide you with compensation for all study participation up to that point. Participants will receive 
partial compensation for partial completion of study appointment measures. 
You will be compensated for your time via ClinCard, which is a specially designed debit card for clinical research.
Greenphire, the company which developed the ClinCard, will act as an agent of Rutgers University to manage the 
payment. You will be given a Greenphire ClinCard, which is a debit card that your study payments are loaded onto 
following completion of study visits. When a study visit is completed, the payment will be approved and loaded 
onto your card. The funds will be available every Friday during the time of your participation, unless the study 
coordinator advises you that it may take a little longer. You may use the ClinCard as you choose, including at 
grocery stores, restaurants, and to retrieve cash from major banks. You will be issued one ClinCard for the duration 
of your study participation. If your card is lost or stolen, you can contact ClinCard support at (866) 952-3795. This 
phone number is also on the back of the card. If you do need a replacement card and you obtain it directly through 
the ClinCard customer support service, it will be mailed to your address. In that event, the balance from your lost 
card will be loaded onto your replacement card, minus a $7 replacement fee charged by the customer support 
service. Or, you may request a replacement card during your next visit with your study coordinator, who will 
provide you with a replacement card for a fee of $3.50, which will be subtracted from your ClinCard balance.
In order to participate in this ClinCard program, as a part of the study, Greenphire will collect information about 
you, including your name, address, telephone number, next appointment date, date of birth, social security 
number, email address, if applicable, and your study subject ID. All information is stored in a secure fashion and 
will be deleted from Greenphire's system once the study has been completed and the funds on your ClinCard have 
been exhausted. Your information will not be shared with any third parties and will be kept confidential.
If you receive $600 or more in a calendar year in total stipend payments from this study, or from other Rutgers’s 
studies or programs, Rutgers University will issue to you an IRS Miscellaneous Income Form 1099, indicating the 
total amount of the payments you received in that tax year. Your decision to receive the stipend payments through 
ClinCard or in another payment form will not affect Rutgers University’s issuance of the Form 1099.
You may opt to receive cash instead of signing up for ClinCard. If you choose to receive cash, you will be paid 
during your in-person visits which will occur at the end of Session 1, 1 Month Follow Up, and 3 Month Follow Up.
How will information about me be kept private or confidential?
Your participation in this research is confidential. Private health information including data regarding physical 
health, mental health, and substance use will be linked to an arbitrary study identification number. However, a 
limited amount of information will be stored in a password-protected file in such a manner that will link your 
identity and your responses. The information in this file is limited to your assigned study ID, first and last name, 
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 8 of 12
your contact information (phone number and email address), and date of participation. Please note that this 
information will be stored separately from study data coded by your arbitrary study number. 
Five years after the conclusion of the study, any source linking your data to your personal identity will be destroyed 
and only the de-identified data will be kept. 
However, if you express suicidal thoughts or plans of any type, or if you express intent to seriously harm others, in 
the answers to our questions, we will do all that we can to maintain your safety and the safety of others, in which 
case the confidentiality limits described may be broken. To the best of our ability, we will seek your cooperation in 
making the report and provide you with referral information to local providers in the community with expertise in 
the treatment of problems related to your expression of intent to harm yourself or others. 
If information from this study is published or presented at scientific meetings, your name and other personal 
information will not be used. The research team and the Institutional Review Board at Rutgers University, who is 
responsible for supervising our research, are the only parties that will be allowed to see the data. If a report of this 
study is published, or the results are presented at a professional conference, data will be presented anonymously. 
Per Federal Regulations, study data will be retained for three 
years at which point the file linking participant names to arbitrary study IDs will be destroyed and remaining data 
will be anonymized. 
This research is covered by a Certificate of Confidentiality from the National Institutes of Health. Researchers with 
this Certificate may not disclose or use information, documents, or biospecimens that may identify you 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 you have consented for this use. Information, 
documents, or biospecimens 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 
abuse or communicable diseases but not for federal, state, or local civil, criminal, administrative, legislative, or 
other proceedings, see below); if you have consented to the disclosure, including for your medical treatment; or if 
it is used for other scientific research, as allowed by federal regulations protecting research subjects. 
The Certificate cannot be used to refuse a request for information from personnel of the United States federal or 
state government agency sponsoring the project that is needed for auditing or program evaluation by the National 
Institute on Drug Abuse, which is funding this project or for information that must be disclosed in order to meet 
the requirements of the federal Food and Drug Administration (FDA). You should understand that a Certificate of 
Confidentiality does not prevent you from voluntarily releasing information about yourself or your involvement in 
this research. If you want your research information released to an insurer, medical care provider, or any other 
person not connected with the research, you 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.
A description of this clinical trial is available on http://www.ClinicalTrials.gov, as required by U.S. Law. This website 
will not include information that can identify you. At most, the website will include a summary of the results. You 
can search this website at any time
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 9 of 12
Apps are used to store data in a secure and encrypted form. Although every reasonable effort has been taken, 
confidentiality during internet communication procedures cannot be guaranteed and it is possible that additional 
information beyond that collected for research purposes may be captured and used by others not associated with 
the study. 
What will happen if I do not wish to take part in the study or if I later decide not to stay in the study? It is 
your choice whether to take part in the research. You may choose to take part, not to take part, or you may 
change your mind and withdraw from the study at any time.
If you do not want to enter the study or decide to stop taking part, your relationship with the study staff will not 
change, and you may do so without penalty and without loss of benefits to which you are otherwise entitled.
You may also withdraw your consent for the use of data already collected about you, but you must do this in 
writing to Teresa M. Leyro, Ph.D. at 848-445-2090 or teresa.leyro@rutgers.edu. 
Additionally, we have the right to withdraw you from the study at any time in such cases as: 
If we determine that you gave us incorrect data that fall under exclusion criteria.
You are not able to fill out required questionnaires or obey study requirements. 
You become pregnant.
Who can I contact if I have questions?
If you have questions, concerns or complaints about the research, wish more information or if you feel you may 
have suffered a research related injury, you can contact the Principal Investigator: Teresa M. Leyro, Ph.D., 
Psychology Department, at 848-445-2090 or teresa.leyro@rutgers.edu.
If you have questions, concerns, problems, information or input about the research or would like to know your 
rights as a research subject, you can contact the Rutgers IRB Office at: (973) 972-3608 or (732) 235-9806 or (732) 
235-2866, or email us at IRBOffice@research.rutgers.edu, or write us at 335 George Street, Liberty Plaza Suite 
3200, New Brunswick, NJ 08901.
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 1 of 12
AGREEMENT TO PARTICIPATE
Subject Consent:
I have read this entire consent form, or it has been read to me, and I believe that I understand what 
has been discussed.  All of my questions about this form and this study have been answered.  I agree 
to take part in this study.
Subject Name (Print):
Subject Signature:
Date:
Subject Compensation:
I am choosing the following as my form of compensation throughout the study:
______ClinCard
______Cash
Subject Name (Print):
Subject Signature:
Date:
Signature of Investigator/Individual Obtaining Consent:
To the best of my ability, I have explained and discussed all the important details about the study 
including all of the information contained in this consent form.  
Investigator/Person Obtaining Consent (Print):
Signature:
Date: 
ADDENDUM: CONSENT TO AUDIO/VISUALLY RECORD OR 
PHOTOGRAPH SUBJECTS 
You have already agreed to take part in a research study entitled: Open Trial of Breath Training for 
Smoking Cessation conducted by Teresa M. Leyro, Ph.D.  We are asking your consent to allow us to 
audiotape your diagnostic interview and video and/or audio record your intervention sessions you as part 
of the research. You do not have to consent to be recorded to take part in the main research. 
The audio recording(s) of your diagnostic interview will be 
used to ensure reliability of diagnoses by the research team and as a teaching tool for new members of 
the team receiving training in the administration of diagnostic interviews. The recordings of your 
intervention sessions will be used to ensure accurate delivery of the intervention and to provide feedback 
to study clinicians.
The recording(s) may include the following information that can identify you: the arbitrary number that will 
be assigned to your data in order to ensure confidentiality. If you say anything that you believe at a later 
point may be hurtful and/or damage your reputation, then you can ask the interviewer to either remove 
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 1 of 12
that portion of the recording, rewind the recording and record over such information if the virtual platform 
that is being used allows, OR you can ask that certain text be removed from the dataset/transcripts.  
The recording(s) will be stored in password protected files, on password protected computers kept in 
locked rooms belonging to the lab. The recordings will be kept until reliability analyses have been 
completed and destroyed upon termination of data analytic procedures for the current investigation. The 
recording(s) will not be used by us or distributed to investigators for other research.  
Your signature on this form permits the investigator named above to record you as described above 
during participation in the above-referenced study. The investigator will not use the recording(s) for any 
other reason than that/those stated in the consent form without your written consent. 
AGREEMENT TO BE RECORDED
Subject Name (Print):______________________________________________________________ 
Subject Signature ________________________________   Date ______________________
Investigator/Person Obtaining Consent Name (Printed):___________________________________
Signature ________________________________________ Date ______________________
SMART PHONE, TABLET, 
OR COMPUTER LENDING 
ADDENDUM TO CONSENT FORM
You have already agreed to participate in a research study entitled Open Trial of Breath Training for Smoking 
Cessation conducted by Teresa M. Leyro, Ph.D.  Please sign below to acknowledge that you understand the terms 
of the smartphone, tablet, or computer lending agreement below.
1)
If you do not own a smartphone or computer which supports the Inner Balance application and video 
conferencing applications (i.e., Zoom) used in this study, we may lend you a device for use during remote 
teletherapy and at-home practice for the duration of the study. 
2)
You agree to return the device at the conclusion of the study (15 week follow-up visit) or if/when you 
withdraw from the study, whichever comes earlier.
3)
If you withdraw from the study prior to full completion (15 weeks), you will receive full compensation for 
all research participation up to the point of the device’s return. If you do not return the smartphone, 
tablet, or computer, you will not receive further compensation. If you do not return the device, you will 
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Department of Psychology
teresa.leyro@rutgers.edu
Tillett Hall
Rutgers, The State University of New Jersey
p. 732-659-4283 
53 Avenue E
f. 848-445-0036
Piscataway, NJ 08854
Protocol Title: Open Trial of HRVB-SCT
Protocol Version Date: v10, 12/20/22
                                                   
Page 1 of 12
not receive the final compensation, as we will be unable to retrieve study data—an integral part of your 
study participation.
4)
If you complete the study, you will receive the $50 attendance compensation and up to $50-100 
attendance bonus based on whether you attended 6/7 sessions or every session, contingent upon return 
of the borrowed smartphone, tablet, or computer.
Your signature on this form indicates that you understand the terms of the lending agreement for the smartphone, 
tablet, or computer to be used in the above-referenced study.  The investigator will not use the data retrieved 
from the device for any other reason than that/those stated in the consent form without your written permission.  
  
_______________________________
Date
 Participant's Printed Name 
Participant’s Signature for Consent
______________              _____________________________
_______________________________
Date
ABUSA Investigator’s Printed Name
ABUSA Investigator’s Signature
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