Clinical trial NCT03972137
Conditions: Tobacco Smoking
Keywords: Smoking Cessation Heart rate variability biofeedback
Sponsor: Rutgers, The State University of New Jersey
Start date: 2019-04-24; Completion date: 2020-02-20
Enrollment: 10 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Open trial of heart rate variability biofeedback as an adjunct to individualized smoking cessation counseling (SCT) plus transdermal nicotine replacement patch (NRT) in smokers with elevated emotional distress.

Detailed description:
The investigators propose to develop and pilot test heart rate variability biofeedback (HRVB) for smokers with elevated emotional distress as an adjunct to individual smoking cessation counseling (SCT) and transdermal nicotine patch (NRT). In this open trial, all participants received the active intervention. Findings will be used to refine the protocol in advance of a subsequent Phase III randomized clinical trial.

Arms: arm 1: All participants in this open trial received individualized cognitive-behavioral smoking cessation treatment (SCT), up to 8 weeks of the transdermal nicotine patch (NRT) and individualized heart rate variability biofeedback (HRVB).
Interventions: intervention 1: Cognitive-Behavioral Smoking Cessation intervention 2: Heart Rate Variability Biofeedback (HRVB) intervention 3: Transdermal Nicotine patch
Intervention descriptions: intervention 1: Participants were 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: All participants were provided with individualized training in resonance breathing using biofeedback to help improve self-regulation. intervention 3: All participants were offered up to eight weeks of transdermal nicotine patch, beginning on their quit date.

Protocol documents:
Prot_SAP_003.pdf: 
 
 
 
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PI Name: Leyro 
Protocol Title: HRVB-SCT 
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 INTERVENTIONAL 
RESEARCH PROTOCOL TEMPLATE 
(HRP-503a) 
 
 
 
INSTRUCTIONS 
 
This template should be used by biomedical and social-behavioral researchers conducting research which 
subjects are assigned to receive one or more interventions so that the researchers can evaluate their 
effects.  (e.g. clinical trials, CBT, Behavioral Modification studies, or randomized outcome studies) 
 
Sections in red may not be applicable to your research: you may replace the instructional text 
with “N/A”.  
 
As you are writing the protocol, remove all instructions in blue italics so that they are not 
contained in the final version of your protocol. 
 
 
STUDY INFORMATION 
Title of Project: Development and Pilot Investigation of Heart Rate Variability Biofeedback for 
Smoking Cessation 
Principal Investigator:  
 
Name: Teresa M. Leyro, Ph.D. 
Division & Department: Psychology 
Contact Information: Room 539, Tillett Hall, 53 Avenue E., Piscataway, NJ 08854 
Telephone Number & Email Address: 848-445-2090, teresa.leyro@rutgers.edu 
 
 
PROTOCOL VERSION AND DATE: 5, 11/5/19 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
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Table of Contents  
Skip To Section: Hold CTRL + Click (Below) To Follow Link in Blue 
 
1.0 
Research Introduction 
 
 
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 
Primary Specimen Collection 
 
 
1.9 
Interviews, Focus Groups, or Surveys 
 
 
1.10 Timetable/Schedule of Events 
 
 
2.0 
Project Management 
 
 
2.1 
Research Staff and Qualifications 
 
 
2.2 
Resources Available 
 
 
2.3 
Research Sites 
 
 
3.0 
Multi-Site Research Communication & Coordination 
 
 
3.1 
Outside Research 
 
 
4.0 
Research Data Source/s 
 
 
4.1 
Primary Data – Subjects and Specimens 
 
 
4.2 
Subject Selection and Enrollment Considerations 
 
 
4.3 
Subject Randomization 
 
 
4.4 
Secondary Subjects 
 
 
4.5 
Number of Subjects 
 
 
4.6 
Consent Procedures 
 
 
4.7 
Special Consent Populations 
 
 
4.8 
Economic Burden and/or Compensation For Subjects 
 
 
4.9 
Risks to Subjects 
 
 
4.10 Secondary Data – Record/Chart Reviews, Databases, Tissue Banks, Etc. 
 
 
4.11 Chart/Record Review Selection 
 
 
4.12 Secondary Specimen Collection 
 
 
5.0 
Special Considerations 
 
 
5.1 
Health Insurance Portability and Accountability Act (HIPAA) 
 
 
5.2 
Family Educational Rights and Privacy Act (FERPA) 
 
 
5.3 
NJ Access to Medical Research Act 
 
 
5.4 
Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations) 
 
 
6.0 
Research Data Protection and Reporting 
 
 
6.1 
Data Management and Confidentiality 
 
 
6.2 
Data Security 
 
 
6.3 
Data Safety And Monitoring 
 
 
6.4 
Reporting Results 
 
 
6.5 
Data Sharing 
 


 
 
 
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7.0 
Data and/or Specimen Banking 
 
 
8.0 
Other Approvals/Authorizations 
 
 
9.0 
Bibliography 
 
 
1.0 Research Introduction 
 
1.1 Purpose/Specific Aims 
The purpose of the study is to conduct a pilot trial to examine the effects of heart rate variability 
biofeedback as a smoking cessation treatment adjunct for smokers with moderate anxiety and/or 
depression symptoms. 
 
A. Objectives  
The present investigation is an uncontrolled pilot study of a heart rate variability (HRV) biofeedback 
smoking cessation treatment (HRVB-SCT) or smokers with moderate levels of anxiety or depression. This 
study is designed to develop, refine, and pilot test HRVB-SCT for daily, nicotine dependent smokers, with 
elevations in anxiety and depression symptoms. Findings will be used to further develop and refine 
patient and clinician manuals for HRVB-SCT to be used in a subsequent randomized clinical trial.  
The goals are to: (a) develop and refine patient and clinician manuals for HRVB-SCT in smokers with 
comorbid emotional psychopathology; (b) understand unique concerns in this patient group that may 
affect treatment fidelity and participant adherence; and (c) complete two open trials of 5 smokers each 
with moderate levels of affective distress in each (n=10) and use observations to inform a subsequent 
randomized clinical trial. 
B. Hypotheses / Research Question(s) 
The main study hypothesis is that HRVB will be a feasible and acceptable accompaniment to standard 
SCT in smokers with elevated emotional distress. We hope to identify and address processes that may 
affect treatment delivery fidelity and patient adherence. We expect that information gleaned from the 
open pilot trial will lead to changes in patient and clinician manuals. Finally, we expect that participants 
will make a quit attempt while enrolled in the open trial, and will report reductions in anxiety and 
depressive symptoms.  
1.2 Research Significance (Briefly describe the following in 500 words or less): 
 
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 I study will develop and pilot test an 
integrated, biobehavioral, transdiagnostic smoking intervention for smokers with moderate emotional 
distress (i.e., elevated mood/anxiety symptoms). 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; 


 
 
 
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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 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.  
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) the current proposal seeks to develop and pilot test HRVB as a treatment adjunct for standard 
smoking cessation treatment (HRVB-SCT) in daily smokers with moderate emotional distress. The 
proposal will use a staged model for developing and standardizing behavioral interventions, as indicated 
by NIDA. The first year of the project will focus on drafting, piloting, and modifying an integrated HRVB 
smoking cessation treatment (HRVB-SCT) and assessing feasibility of treatment delivery, fidelity, and 
potential for improving smoking cessation outcomes and reducing emotional distress. Data collected 
during this time will inform the next stage of the study, which will involve completion a two-arm pilot 
randomized controlled trial (RCT) of HRVB-SCT versus a breath awareness training (BAT-SCT) sham to 
evaluate smoking and emotional distress outcomes and explore transdiagnostic physiological and 
cognitive-affective treatment mechanisms.   
1.3 Research Design and Methods 
 
Overview: The current proposal represents of the initial phase of treatment development and will 
involve writing, pilot testing, and refining the HRVB-SCT patient and clinician treatment manuals. We will 
pilot test the manual in two open trials including 5 participants each (n=10) to assess feasibility in 
preparation for a subsequent pilot randomized clinical trial, to be conducted at a later date. 


 
 
 
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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. All participants will receive HRVB-SCT. 
Pre-Study Telephone Screening: Upon initial contact of the ABUSA lab, prospective participants will 
complete a phone interview to assess current smoking status, history, screen for key health exclusionary 
criteria (e.g., substance use, cardiac health, and history of psychotic spectrum symptoms), and assess 
current depression, anxiety and stress, using the DASS-21. Participants who appear to meet study 
inclusion/exclusion criteria will be scheduled for a baseline appointment to occur within the next week. 
Reason for exclusion will be tracked for ineligible participants, and they will be referred to the Rutgers 
Tobacco Dependence Program, a free local clinic offering evidence-based pharmacological and individual 
and group cessation treatments. 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.   
HRVB Intervention: Intervention sessions will last between 30 and 60 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 10 sessions of HRVB over the course of 7 weeks. Sessions are front-loaded with two sessions 
occurring before homework assignment to ensure accurate training, and four prior to the quit date, to 
promote quit day success (see Table 1). Clinicians will be trained in the application of HRVB including 
instructing participants in how to breathe with a pacer and using Thought Technology software to teach 
participants how to follow a cardiotachometer to achieve breathing at their resonance frequency (i.e., 
biofeedback), which provides real time display of resonance, peak and trough amplitude of heart rate, 
inter-beat-interval, and respiration data. Clinicians will also be trained in the use of a smartphone 
application, that will be used for at-home practice and recording. This app uses the phone camera light 
as a pulse plethysmograph to obtain estimates of heart rate data. Data will be used primarily for 
homework compliance and in-session to build confidence in home practice. While breathing at the 
prescribed pace, participants will view a waveform on the phone that reflects their heart rate, similar to 
that observed in biofeedback sessions. While following the waveform and practicing learned resonance 
breathing, they are instructed to try to increase the amplitude of heart rate oscillations, which will 


 
 
 
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increase heart rate variability (HRV). Participants will be asked to practice HRV biofeedback 40 minutes 
daily, in bouts of 5-20 minutes. Practicing for 40 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 at-home 
practice, the device allows the investigators to download biofeedback data for quality assessment. 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): As indicated by clinical practice guidelines ((Fiore et al. 2008; Jaen 
et al., 2008), participants will receive transdermal (NRT) patches and counseling for smoking cessation. 
Counseling will be integrated into HRVB sessions. To standardize treatment between-groups, 
independent assessors, who are blind to treatment randomization, will be trained in providing the SCT 
using the National Cancer Institute’s Clear Pathways (NCI, 2013) guide. Each participant will be provided 
with Clear Pathways and be given weekly assignments. SCT will be provided for 20 minutes at weeks 1a, 
2a, 3a, and 5 (see Table 1). Participants will receive 8 weeks of NRT and will be instructed to place their 
first nicotine patch upon waking on their quit day (Fiore et al. 2008). Dosage Schedule: Individuals 
smoking >10 cigarettes/day will receive the 21 mg/day NRT patch for 4 weeks, followed by the 14 
mg/day NRT patch for 2 weeks, and complete their course of NRT treatment with the 7 mg/day NRT 
patch for 2 weeks. Individuals smoking ≤10 cigarettes/day will receive the 14 mg/day NRT patch for 6 
weeks followed by the 7 mg/day NRT patch for 2 weeks. To increase compliance, dosing will be 
monitored and adjusted as needed to ensure adequate dosing and minimize adverse effects. 
 
Week 0 Visit (Baseline): At Week 0, potential participants will come to the lab and meet with an 
independent assessor who will verify smoking status via CO analysis of breath sample, confirm study 
inclusion/exclusion criteria, and obtain written informed consent. To ensure participants do not meet 
criteria for exclusionary bipolar, psychotic spectrum disorders, or severe substance use disorders, the 
independent assessor will use a short diagnostic structured interview. Next, participants will complete a 
battery of self-report measures on Qualtrics, an online survey portal. In addition to core 
inclusion/exclusion criteria, questionnaire data will be used to assess general health, a range of smoking 
relevant processes, other substance use, and self-reported and behaviorally indexed distress tolerance. 
Following Week 0, participants who remain eligible will be scheduled for their first intervention session 
the following week.  
Recording Sessions: During sessions 1, 4, 8, and 10, we will record several 5-minute physiological 
segments in order to assess both within and between-session changes in cardiac vagal parameters (i.e., 
vagal tone and flexibility). Data will be collected via two methodologies. First, participants will be 
hooked up to Mindware’s integrated psychophysiological system to obtain continuous measures of 
electrocardiograph (ECG) and impedance cardiograph (IC), which allows for the extraction of respiration 
data necessary to compute HF-HRV (BioNex 8SLT Biolab Acquisition Application, MindWare 
Technologies, Gahanna OH). Following a 5-minute resting period, 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. Mindware software will be used to score data, and 


 
 
 
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digitized ECG signals will be examined to correct misidentified R spikes. This cognitively demanding dot-
tracking task has reliably been used in the past as an index of vagal flexibility 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. 
During HRVB training, participants will be connected to Thought Technology Infiniti System 
(www.thoughtechnology.com) to obtain continuous respiration and ECG data during several 5-minute 
rest and HRVB periods. HF-HRV data will be scored using Cardiopro software. This data will supplement 
our core indices of vagal tone and flexibility that will be obtained using Mindware. During each session, 
participants will be asked to complete several measures to assess pre- and post-session positive and 
negative affect, substance use, importance of quitting and confidence ratings, and smoking withdrawal 
craving. In addition, both participants and therapist will provide ratings to assess acceptability and 
feasibility of the intervention.  
 
Weekly Assessments: During each session, participants will again be asked to complete several 
measures to assess pre- and post-session positive and negative affect, substance use, importance of 
quitting and confidence ratings, and smoking withdrawal craving. Also, participant and therapist ratings 
to help assess acceptability and feasibility of the intervention will be made.  
Follow-up Assessments: Post-quit assessments will occur during sessions eight and ten (2-weeks and 1-
month, post quit), and 3-months post quit date. Abstinence will be verified via self-report and carbon 
monoxide analysis of breath sample and confirmed by saliva cotinine.  
 
Table 1. Summary of Integrated HRVB-SCT Intervention Protocol by Session 
 
Week 
Session 
Core Components 
Time 
Pay 
Week 1a 
HRVB S1 
• 
Intervention Overview 
• 
Recording sessionR 
• 
Goal: Introduce HRVB Breathing using pacer 
40 
$25 
 
$15 app 
practice 
SCT  
• 
SCT program introduction and orientation to 
Clear Pathways 
• 
Goals: Understanding why you smoke, 
health effects of smoking/quitting, set quit 
date (week 3) 
20 
Week 1b 
HRVB S2 
• 
Biofeedback practice sessionB 
• 
Goal: Introduce cardiotachometer 
biofeedback 
• 
Assign homework: Practice 2x/day for at 
least 20m 
30 
Week 2a*  HRVB S3 
• 
Biofeedback practice sessionB 
• 
Goal: Cross-reference Camera HRV and 
cardiotachometer 
30 
$25 
 


 
 
 
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• 
Assign homework: Practice 2x/day for at 
least 20m 
$15 app 
practice 
SCT  
• 
Review homework 
• 
Goals: Increase motivation to quit, plan for 
quit day, introduce NRT and provide 
instructions 
20 
Week 2b 
HRVB S4 
• 
Recording sessionR  
• 
Assign homework: Practice 2x/day for at 
least 20m 
40 
 
SCT 
• 
Plan for quit day, introduce NRT and provide 
instructions 
 
 
Week 3a  
(Quit day) 
HRVB S5 
• 
Biofeedback practice sessionB 
• 
Goal: Assess adherence, motivation, trouble-
shoot  
• 
Assign homework: Practice 2x/day for at 
least 20m 
30 
$10 
 
$15 app 
practice 
SCT  
• 
Assess quit status via CO analysis101 
• 
Highlight successes, trouble-shoot/learn 
from failures 
• 
Promote quit resumption if failed 
• 
Assess NRT use side effects, 
questions/concerns, adherence 
20 
Week 3b  
HRVB S6 
• 
Biofeedback practice sessionB 
• 
Goal: Make post-quit adjustments to HRVB, 
assess adherence, motivation 
• 
Assign homework: Practice 2x/day for at 
least 20m 
30 
Week 4* 
HRVB S7 
• 
Biofeedback practice sessionB 
• 
Goal: Assess adherence, motivation, trouble-
shoot  
• 
Assign homework: Practice 2x/day for at 
least 20m 
30 
$10 
 
$15 app 
practice 
Week 5  
(2w post 
quit) 
HRVB S8 
• 
Recording sessionR  
• 
Assign homework: Practice 2x/day for at 
least 20m 
40 
$25 
 
$15 app 
practice 
SCT  
• 
Goal: Assess abstinence status, revise quit 
plan to maintain abstinence or resume 
cessation, provide additional NRT 
20 
Week 6*  
HRVB s9 
• 
Biofeedback practice sessionB 
• 
Goal: Assess adherence, motivation, trouble-
shoot  
• 
Assign homework: Practice 2x/day for at 
least 20m 
30 
$10 
 
$15 app 
practice 


 
 
 
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Week 7  
(1m post-
quit) 
HRVB S10 
• 
Recording sessionR  
• 
Goal: Obtain commitment to continue 
practice  
40 
$25 
 
$15 app 
practice 
SCT 
• 
Goal: Brief assessment abstinence status, 
offer of support, encourage resumption, 
provide NRT 
20 
Week 16  
(3m post-
quit) 
HRV  
• 
Recording sessionR 
40 
$50 
 
$15 for 
every 
week of 
app 
practice 
SCT 
• 
Assess abstinence via CO and cotinine 
10 
RRecording session (respiration, ECG, blood volume sensor, skin temperature, and skin conductance); 
BBiofeedback practice session (respiration and ECG) 
Participants will be paid up to $15 each week for at-home breathing practice during weeks 1-15. 
Participants will be paid $1 per each 20-minute at-home breathing practice session as recorded with the 
app. Participants should practice twice daily, for a total of up to $2 per day. If participants complete 2 
sessions per day for all 7 days, they will receive a $1 bonus, for a total possible of up to $15 weekly. 
*At the discretion of the study team, participants may be given the option to complete sessions 3 (week 
2a), 7 (week 4), and 9 (week 6) at home with therapist support via teleconferencing (e.g., via computer, 
phone, etc.). 
 
Table 2. Study Measures Table 
Phone Screen: 
1) Interview: The phone screen will be administered prior to study enrollment to help determine 
whether interested participants are eligible. 
2) 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. 
3) 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. 
In Person and Qualtrics Measures: 
Participant Information Sheet to confirm inclusion/exclusion criteria 
Medical Screening Questionnaire to confirm inclusion/exclusion criteria 
Participant Contact Info to document best means to contact participant for study 
communication *includes request for permission to text* 
Demographic InformationB to confirm inclusion/exclusion criteria. 


 
 
 
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Short-form Health Survey133 to assess quality of life in regard to health.  
Credibility and Expectancy QuestionnaireB 134 to assess treatment expectancy and credibility of 
intervention rationale (modified for the purposes of this study). 
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 provide ratings of participant engagement, comfort in 
applying intervention, confidence in applying intervention, and perceived accuracy of 
intervention. 
Exit interview 
Smoking History Questionnaire (SHQ) B135–30-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. 
Fagerström Test of Cigarette Dependence (FTCD)B 136-138 –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 (scoredas 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. 
Thoughts about Abstinence W139-141 to assess commitment to complete abstinence including 
importance and confidence.    
Minnesota Nicotine Withdrawal Scale W  142 
Questionnaire of Smoking Urges W,  143 
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. 
Smoking Abstinence Questionnaire (SAQ)--55-item self-report questionnaire which assesses 
expectancies related to smoking abstinence. Participants usea7-point Likert scale (0=not likely at 
allto 6=extremely likely) to indicate perceived feelings, thoughts, behaviors that will be 
experienced as a result of quitting. The psychometric properties and reliability of this scale have 
been reported. 
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.  
Wisconsin  Inventory  of  Smoking  Dependence  Motives  (WISDM-68)--68-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-dimesnional 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  proved  to  be  good. 


 
 
 
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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. 
Timeline Followback Winterview144-146 will be used to assess ongoing cigarette, e-cigarette, patch, 
alcohol, and other tobacco and substance use.  
Depression Anxiety Stress Scale (DASS-21) W  116 to assess for past week symptoms of depression, 
anxiety, and stress. 
Positive and Negative Affect Schedule W   147,148 to assess current emotional states before and 
after intervention sessions.  
Distress Intolerance Index (McHugh & Otto) B, R 149 to assess participants’ perceptions of their 
ability to tolerate mental distress.  
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.106 
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.107 
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. 
Distress Tolerance Scale (DTS) -- 15-item scale used to assess participants’ perception of their 
ability to tolerate mental distress. Items (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.127 
Frustration Discomfort Scale (FDS) -- 35 items 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.128 


 
 
 
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Perceived Stress Scale (PSS10) – 10 items designed to measure 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. 
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.139,140,141,142 
Adult ADHD Self-Report Screening Scale (ASRS-5) 6 items 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. 
The Urgency, Premeditation, Perseverance, and Sensation Seeking Impulsive Behavior (UPPS-P) 
-- 20-item measure assesses characteristics of personality, such as how rashly participants 
respond in response to negative moods, and determines how they may contribute to impulsive 
behavior.134 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 consistency135 and convergent and divergent validity.136 
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. 
Cigarette Purchase Task (CPT) is a 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).    
 
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 
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. 131 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.132 
Ratings of Session Protocol Adherence and Examination of Physiological Data for Intervention 
Accuracy: To assess treatment fidelity.    
 


 
 
 
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HRVB Clinician Training: Training will include careful assessment of clinician adherence, defined as using 
the correct skills as well as competence, i.e., 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, and will role-play managing 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. Designated 
study assessors will be asked to code 25% of the initial eight HRVB sessions provided to first cohort (n=5) 
of participants (Muse & McManus, 2013). Fidelity will additionally be assessed by Co-Is E. Vaschillo and 
P. Lehrer who will review recorded physiological data from sessions 1, 4, 8, and 10 to rate whether 
participants, under therapist instruction, received adequate resonance between heart rate and blood 
pressure, central to the success of the intervention. 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 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, to promote accurate HRVB application.  
HRVB Training and Manual Refinement: Study clinicians will receive intensive training from our team 
who will provide ongoing clinical supervision and consultation. In addition to prescribed study measures, 
study 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 (completing <75% of at-home practice sessions; and/or at-
home sessions average < 10m of practice) will be asked a structured series of questions by their clinician 
to help determine what is promoting or obstructing adherence. Together, a combination of qualitative, 
interview, objective, and self-report data will be consolidated and provided to the research team and 
will be used to adapt HRV-SCT intervention accordingly.  
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 two in-person training sessions, and homework will not be assigned until after the second 


 
 
 
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session.  We hope that this prevents formation of bad habits and increases the likelihood of adherence. 
To address adherence, we have put in place several strategies. Participants who do not have iPhones 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 10; 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. 
Compensation: Participants will receive up to $455 in total study compensation. This includes $10 to 
$25 per week, depending on whether they include a recording session, $50 for their 3-month follow-up 
appointment, and a $50 bonus for attending all sessions. Additionally subjects will be paid up to $15 
each week for at home breathing practice from weeks 1-15.  
B.  What data points will be collected including long-term follow-up? 
Data will be collected over the course of 16 weeks, which include ten in-person laboratory sessions (Tables 
1), and will include interview, self-report, behavioral, and psychophysiological assessment.   
 
C.  Define the duration of the study and the length of time each subject will participate in the study.  
Following the baseline session, which will last 1-3 hours, participants will be asked to complete 10 
intervention sessions over the course of 7 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.  Describe any primary and secondary study or safety endpoints 
N/A 
 
1.4 Preliminary Data 
N/A 
 
1.5 Sample Size Justification 
The goal of this study is for n=10 to complete at least one intervention session. We will consent up to 
n=15 participants for this study as we anticipate that a portion of individuals attending a Week 0 
appointment will not be eligible for the intervention, based upon our extensive inclusion/exclusion 
criteria. The target sample size of n=10 for the current project was selected to allow our study team to 
develop, refine, and test, via open trial, HRVB-SCT on two cohorts of 5 participants, prior to scaling the 
intervention for a larger randomized clinical trial. Data will not undergo rigorous statistical testing and 
will instead be examined qualitatively, and used to adjust our study protocol. 
 


 
 
 
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1.6 Study Variables 
A. Independent Variables, Interventions, or Predictor Variables  
All participants will receive the active intervention, HRVB-SCT as part of this uncontrolled open trial. 
 Please see 1.3 Research Design and Methods for details. 
 
B. Dependent Variables or Outcome Measures  
The following list of measures will be used to assess therapist credibility, treatment fidelity and 
acceptability, and participant adherence. We will also examine treatment utility via examination of 
whether participants make a quit attempt, as well as changes in withdrawal, urges, overall use of 
cigarettes, and anxiety and depression symptoms.  
 
Credibility and Expectancy Questionnaire to assess treatment expectancy and credibility of 
intervention rationale. 
Post-Intervention Acceptance Ratings (Participant and Therapist versions): To assess treatment 
acceptability.  
Ratings of Session Protocol Adherence and Examination of Physiological Data for Intervention 
Accuracy: To assess treatment fidelity.    
Minnesota Nicotine Withdrawal Scale  
Questionnaire of Smoking Urges  
Timeline Followback interview will be used to assess ongoing cigarette, e-cigarette, patch, alcohol, 
and other tobacco use.  
Depression Anxiety Stress Scale (DASS-21) to assess for past week symptoms of depression, 
anxiety, and stress. 
 
1.7 Drugs/Devices/Biologics  
Nicotine replacement therapy. The nicotine patch is an accepted, FDA approved treatment for nicotine 
dependence. Patches are available over-the-counter (OTC) without a prescription. Study participants will 
be provided with information written at a 6th grade level describing the proper use of the nicotine 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) Storage and accountability. We will store nicotine replacement therapy (NRT) in original 
packaging (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.  
b) Inventory. We will use an NRT inventory log to document the Lot # and Expiration date of each 
box of NRT. 
c) 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. 
 


 
 
 
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1.8 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 Interviews, Focus Groups, or Surveys  
N/A 
 
1.10 Timetable/Schedule of Events 
The proposed timeline is based on project completion within three years.  
 
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: Min-Jeong Yang, Mark Versella, and Allison Borges have each completed 
extensive training in evidence-based smoking cessation treatment and will serve as study clinicians and 
independent assessors. 
Research Coordinator: Amy Gong has participated in several studies in our lab. She will be responsible 
for study coordination, including scheduling, compensation, dispensing NRT, and randomization.  
Key Study Personnel: Drs. Leyro, B. Vaschillo, and Lehrer will be responsible for clinical training and 
supervision of personnel and Dr. Leyro will provide general project oversight, including training in all 
study procedures, IRB correspondence, documentation of all adverse events, and data safety monitoring 
board communication. Drs. Bates and E. Vaschillo 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.   
Undergraduate Research Assistants: Undergraduate RAs will undergo extensive training in addition to 
their prior experience in the lab and will assist in screening potential participants, scheduling 
appointments, recording physiological data and communicating select study information to participants.  
Table 4. Timeline for Proposed Research  
Months  
Goals  
1-3  
Draft initial manual; obtain feedback from consultants; revise manual; conduct staff 
training, begin recruitment.  
4-5 
Conduct open trial for cohort 1 (n=5) through quit week.   
6 
Initial revisions to protocol. Update IRB of proposed revisions, if applicable. 
7-8 
Cohort 2, open trial (n=5) through week 6. 
9-10 
Finalize protocol revisions, prepare IRB submission for subsequent randomized clinical 
trial. Open trial participants complete 3-month follow-up.  


 
 
 
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2.2 Resources Available 
A. Facilities 
Research will take place in the Principal Investigator’s lab space son at One Spring Street in downtown 
New Brunswick, as well as the 5th floor of Tillett Hall located on the Livingston Campus in Piscataway. 
Facilities include materials necessary for data collection (e.g., physiological monitoring equipment, 
laboratory space, sub-zero freezer). 
B. Medical Or Psychological Resources 
Study risks are minimal and include an increase in distress as a result of the speech tasks; 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 physiological monitoring equipment; abrasions 
should not be more intensive than removal of bandaids.  
 
C. Research Staff Training 
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 study to allow 
for sufficient practicing of necessary procedures. All study staff have previously administered all of the 
aforementioned techniques during prior investigations. 
 
Training will also include careful assessment of clinician adherence, defined as using the correct skills, as 
well as competence, meaning, 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, 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.  
 
Study clinicians will receive intensive training from Drs. Leyro, Lehrer, and B. Vaschillo 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 


 
 
 
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(<75%) will be asked a structured series of questions by their clinician to help determine what is 
promoting or obstructing adherence. Together, a combination of qualitative, interview, objective, and 
self-report data will be consolidated and provided to the research team, and be used to adapt HRV-SCT 
intervention accordingly prior to the Phase II RCT. 
 
3.0 Multi-Site Research Communication & Coordination  
N/A 
 
3.1 Outside Research 
N/A 
 
4.0 Research Data Source/s 
 
4.1 Primary Data-Subjects and Specimens 
N/A 
 
4.2 Subject Selection and Enrollment Considerations  
A. Recruitment Details 
We will consent up to 15 participants from the greater Rutgers, New Brunswick, NJ area with a target of 
n=10 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 over the course of six months 
through posters, leaflets, mailings, online advertisements, community outreach (i.e., meetings with local 
organizations and treatment providers who work with cigarette smokers), and listservs.   
B. Source of Subjects  
Community participants in the greater New Brunswick and Central New Jersey area.  
 
C. Method to Identify Potential Subjects 
Study advertisements will be posted in the greater New Brunswick area and Central New Jersey. Online 
advertisements will be posted via social media platforms and will target potential participants based on 
demographic criteria including age and gender. Advertisements will also be posted in health-related 
clinics and institutes in the area.  
D. 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 


 
 
 
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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) ability to read and speak English fluently, and (4) computer 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) 
self-reported pending legal issue with potential to result in incarceration; (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 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 > 30); (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. 
 
E. Recruitment Materials  


 
 
 
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Prospective participants will be recruited from the greater Rutgers University area in New Brunswick, 
New Jersey via posting flyers in the community and via social media. In addition, information on our 
study will be printed in local and University print and online papers, forums, and listservs.  
F. Lead Site Recruitment Methods 
N/A 
 
4.3 Subject Randomization 
N/A 
 
4.4 Secondary Subjects 
N/A 
 
4.5 Number of Subjects 
A. Total Number of Subjects 
Up to 15 participants will be consented with a target enrollment of n=10.  
 
 
B. Total Number of Subjects If Multicenter Study 
N/A 
 
C. Require Number of Subjects to Complete Research 
N/A 
Please see the response in 4.5.A above. 
D. Feasibility of Recruiting 
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 (e.g., Baker et al(Baker et al., 2007)).  
 
4.6 Consent Procedures 


 
 
 
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A. Consent 
 Documenting Consent 
The PI or supervised/trained RAs will complete all aspects of the consent procedures. Verbal consent will 
be obtained for the initial phone screen. The PI or RA 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, procedure, 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 
N/A 
 Waiver or Alteration of Consent Process  
(i) Waiver or Alteration Details 
N/A 
(ii) Destruction of Identifiers 
N/A 
(iii) Use of Deception/Concealment 
N/A 
 
B. 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 in-person meeting at our research offices, or at the agency at which the participant is 
associated, 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 with the DSMB 
to determine adverse event reporting, and will be detailed in all continuing review procedures.  


 
 
 
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 
 Individual Roles for Researchers Involved in Consent 
PI supervised/trained graduate students and research assistants will complete all aspects of the consent 
procedures.  
 
1. 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.   
 
2. 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.  
 
3. 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.  
 
4.7 Special Consent/Populations 
 
A. Minors-Subjects Who Are Not yet Adults  
 Criteria for Consent of Minors 
N/A 
 Wards of the State 
N/A 
 Parental Permission 
N/A 
 Non-Parental Permission 
N/A 
 Assent Process 
N/A 
 
Non-English Speaking Subjects 
N/A 
1. Process for Non-English Speaking Subjects 
N/A 
 
Short Form Consent for Non-English Speakers 
N/A 
B. Adults Unable to Consent / Cognitively Impaired Adults (for interventional studies) 
 
NJ Law-Assessment of Regaining the Capacity To Consent 
N/A 
 
Capacity To Consent 
N/A 
 
NJ Law-Selecting A Witness  


 
 
 
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N/A 
 
Removing a Subject 
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 the designated DSMB to make a 
determination regarding communicating when and how to communicate information to the IRB or 
funding agency (NIDA). 
 
4.8 Economic Burden and/or Compensation for Subjects 
A. Expenses  
Participants may incur costs of transportation to arrive at the study site. Travel and transportation costs 
will not be reimbursed. 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 $455 in total study compensation. This includes $10 to $25 per week 
depending on whether they include a recording session, $50 for their 3-month follow-up appointment 
(see Table 1), and a $50 bonus for attending all sessions. Additionally subjects will be paid up to $15 
each week for at home breathing practice from weeks 1-15.  
C.  Compensation Documentation 
A signature of participants will be obtained upon the completion of the compensation. 
  
4.9 Risks to Subjects 
A. Description of Subject Risk 
 (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 
interventions.  The most often observed risk is discomfort breathing at a pace that is much slower than 
typical, and worry that one is not inhaling adequate air. To address this potential risk, study clinicians 
will be carefully trained in providing participants with a clear rationale for the procedure, clinical 
management of distress associated with the intervention, and appropriate adjustments to ensure 
participants are able to adhere to the protocol.  
(3) Physiological Recording: All of our sensors record responses from the surface of the body and are 
hence noninvasive, and should not cause the participants any discomfort or physical harm. Patients may 
experience mild discomfort with the application and removal of passive electrodes to monitor their 
physiological parameters. However, we do not anticipate this discomfort to be longstanding. To 


 
 
 
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minimize discomfort, all sensors are placed and removed by study staff that will receive training in 
appropriate placement and removal. 
 (5) 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.   
(6) 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. 
 (7) Breach of Confidentiality: There is a risk that confidential information about a participant may be 
revealed. 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. 
 
B. Procedures for Risks to Embryo, Fetus, and/or Pregnant Subjects 
N/A 
C. Risks 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.  
 
 Risk Of Imposing An Intervention On Subject With Existing Condition 
N/A 
 Other Foreseeable Risks 
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 


 
 
 
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with results in any published or otherwise publicly presented report. Demographic information, including 
information about participants’ age, ethnicity, education, marital status and employment status, will be 
reported using averages and percentages computed over multiple participants and never reported at the 
level of individual participants.  
 Observation And Sensitive Information 
N/A 
 
E. Minimizing Risks 
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 
themself, we will contact Acute Psychiatric Services (855-515-5700). 
 
F. 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.  
 
G. 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 assigned to HRVB will experience additional reductions in anxiety and 
depressive symptoms, and improved physiological health as determined by indices of autonomic 
balance.  
 
H. 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 


 
 
 
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addition, potential participants will not interact with any member of the study team that they have a 
personal or professional relationship with. 
 
I. Research Team Access to Subject Data 
Only IRB approved staff will have access to participant data. All data will be coded by arbitrary study 
number to ensure confidentiality and will be stored in a locked filing cabinet or stored on the lab server 
where access will be password-protected. Data collected online will be de-identified (e.g., associated with 
an arbitrary study ID number) and only accessible to trained study personnel. Consent forms with 
identifying information (names) will be filed separately from actual study data in a separate locked filing 
cabinet. The list linking participant ID with name will be kept in a separate locked cabinet from de-
identified data, and a digital copy will be maintained locally in a password-protected file, located within a 
password-protected database on an encrypted computer. Locked cabinets and the locked office in which 
they are kept will ensure that all data also double-locked. 
 
4.10 Secondary Data – Records/Chart Reviews/Databases/Tissue Banks/etc. 
N/A 
4.11 Chart/Record Review Selection 
N/A 
4.12 Secondary Specimen Collection 
N/A 
 
5.0 Special Considerations 
 
5.1 Health Insurance Portability and Accountability Act (HIPAA) 
N/A 
 
5.2 Family Educational Rights and Privacy Act (FERPA) 
N/A 
 
5.3 NJ Access to Medical Research Act 
N/A 
 
5.4 Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations) 
A.  “Special" Classes Of Subjects 
N/A 
6.0 Research Data Protection and Reporting 
 
6.1 Data Management and Confidentiality 
All copies of records, behavioral tests, audio and video recorded, 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 


 
 
 
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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 the baseline session, 
we will obtain consent, verify inclusion/exclusion criteria, assess smoking status, complete a diagnostic 
interview, 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 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. 
A. Data analysis plan 
The current study is underpowered for statistical examination of intervention effects, which are not the 
primary study aims. Instead, fidelity, adherence, and acceptability of the intervention will be examined 
using data acquired via self-report, physiological, and phone app data from participants, therapist report 
of session quality and ease, and rating of recorded sessions. We will also assess whether participants 
engage in a quit attempt and report decreases in withdrawal, urge, cigarette use, and anxiety and 
depression symptoms.  
B. Power analysis 
N/A The goal of this project (N=10) is to provide preliminary data to examine the feasibility and 
acceptability of a novel smoking cessation intervention.  
 


 
 
 
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C. Securing data 
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. 
D. Quality control 
Qualtrics and Excel databases will be created in such a way as to not allow for out of range data. 
 
In addition, the following strategies will be employed to minimize study attrition and maximize data 
collection: Randomized participants will begin treatment within one week of consent. During the first 
visit, study staff will emphasize the participant’s responsibility for engagement and commitment to their 
quit program and our intervention, reiterate confidentiality, and work to establish strong rapport with 
participants, including discussing their training, expressing enthusiasm to work with the participant, and 
addressing questions and concerns. Study staff will follow a detailed protocol to address participant 
lateness or absenteeism based on work by Hall et al,(Hall et al., 2011; Hall et al., 2009; Hall, Humfleet, 
Reus, Muñoz, & Cullen, 2004; Hall, Muñoz, & Reus, 1994; Hall et al., 1996; Hall et al., 1998) whose 
extended smoking cessation interventions boast retention rates of nearly ~90%.   
Specifically, participants will complete a tracking form to obtain names and contact information, 
including telephone numbers, home, and email addresses of four individuals who may be contacted by 
study staff if we are unable to reach the participant.  
Participants will not be considered lost to follow-up at any data point until they: (1) fail to return three 
calls when messages are left; (2) fail to attend three appointments; and (3) refuse an outreach visit by 
staff.  
If this occurs, we will attempt to obtain smoking data by telephone verification from contacts, and 
encourage completion of questionnaire data via online survey link or mail. Participants will be contacted 
for all assessments independent of whether or not they continued treatment. In addition, at each visit, 
participants will receive a written reminder of their next appointment, and reminder calls/texts will be 
placed 48 and 24 hours prior to study visits that occur one-week apart, and one- and two-weeks prior to 
the 3-month follow-up.   
We anticipate that the majority of study attrition will occur early in treatment or during the follow-up 
period. Accordingly, we have front-loaded intervention sessions during weeks 1 and 2 (see Table 1), 
where clinicians will build rapport and implement psychoeducation strategies and provide a credible 
treatment rationale. In addition to promoting HRVB practice during treatment, we will provide ongoing 
monetary compensation for routine practice during weeks 7 through 16.  
E. Data handling 


 
 
 
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Study data will be linked to an arbitrary study number. Data will not be linked to protected health 
information. Data will only be accessed and handled by IRB approved study personnel and kept in 
password protected databases.  
 
Data will be kept indefinitely to allow for future secondary data analyses, which may require looking at 
original raw data. However, to ensure confidentiality, data will remain coded by an arbitrary study 
number. Data will continue to be stored and a locked office and locked cabinet. Data stored on 
computers will be double password protected. 
 
Dr. Leyro, the study PI, is responsible for the receipt and transmission of data. 
 
Data will not be transported or shared with any individuals aside from named study staff without explicit 
IRB approval. Data will only be accessible on password protected laboratory computers. 
 
6.2 Data Security 
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 separately 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. 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.  
 
6.3 Data and Safety Monitoring  
Dr. Leyro has developed a detailed data safety and monitoring plan and board that can be found in the 
attachment. Please note that the DSMP, submitted to the funding agency (NIH/NIDA) was designed to 
be used for both the open and randomized clinical trial (to be submitted to IRB for approval at a later 
date) phases of the study. 
A. Periodic Data Evaluation 
Please see DSMP 
B. Type of Data Evaluated 
Please see DSMP 
C. Collection of Safety Information 
N/A 
D. Frequency of Data Collection 
Please see DSMP 
E. Reviewer of Data 
Please see DSMP 
F. Schedule of Review of Cumulative Data 
Please see DSMP 
G. Tests for Safety Data 
Please see DSMP 
H. Suspension of Research 
Please see DSMP 


 
 
 
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6.4 Reporting Results 
A. Sharing of Results with Subjects  
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. Individual Results  
N/A 
C. Aggregate Results  
 
N/A 
D. 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. 
 
E. ClinicalTrials.Gov Registration and Data Reporting 
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. 
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, masking 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. 
3. 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 


 
 
 
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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, reporting groups, and 
randomization assignment), demographic and baseline characteristics (e.g., race/ethnicity, 
sex/gender, age, cigarettes smoked daily; total and separated by randomization), key outcome 
measures and analyses, serious and other adverse events, and limitations and caveats.  
 
6.5 Data Sharing   
Please see section 6.4.E. We will follow data sharing mandates in accord with registration on 
clinicaltrials.gov. Our consent form will detail requirements associated with this policy to ensure 
participants are aware of this policy.  
 
7.0 Data and/or Specimen Banking 
N/A 
 
8.0 Other 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  
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.  
Ashare R, Sinha R, Lampert R, et al. Blunted vagal reactivity predicts stress-precipitated tobacco 
smoking. Psychopharmacology. 2012;220(2):259-268. PMID: 21938416 
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.  


 
 
 
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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 
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ICF_002.pdf: 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Heart Rate Variability Biofeedback for Smoking Cessation  
Informed Consent Form  
Date of approval: 10-3-2018  
NCT03972137