AAT + tDCS to Reduce Cue-induced Craving and Smoking Behavior
Phase: NA
Conditions: Smoking Behaviors, Smoking, Cigarette
Sponsor: Cynthia Conklin

Date: Friday, January 17, 2025 12:44:09 PM
Print
Close
View: Pitt SF: Basic Study Information 8.2
Basic Study Information
 
1. * Title of study:
AAT + tDCS to reduce cue-induced craving and smoking behavior
2. * Short title:
AAT+tDCS
3. * Brief description:
Smokers are highly reactive to smoking-related stimuli and report that this cue
reactivity (CR) is a major obstacle to quitting. To date, no pharmacologic methods
attenuate CR, and attempts to diminish it with traditional cue exposure treatment
(CET) have not proven effective. The proposed study will test a highly novel cue-
based smoking treatment adjunct combining an Approach/Avoidance Task (AAT)
with brain stimulation via tDCS applied to the dorsolateral prefrontal cortex (dlPFC)
during personalized multi-cue exposure; the goal of which is to discover an effective
means of reducing cue reactivity and daily smoking, and increasing intent and
confidence to quit, among high treatment-interest smokers.
4. * What kind of study is this?
Single-site study
 
5. * Will an external IRB act as the IRB of record for this study?
  Yes  No
6. * Local principal investigator:
Cynthia Conklin
* Is this your first submission, as PI, to the Pitt IRB?
  Yes  No
7. * Does the local principal investigator have a financial interest related to this
research?
  Yes  No
8. Attach the protocol:
Sponsor/Multicenter/Investigator-initiated protocol
Coordinating Center supplement
Emergency Use Consent/ Protocol/ FDA Form 3926
Exempt Application form
 Document
Category
Date Modified
Document History
There are no items to display

View: Pitt SF: Funding Sources (not integrated with Grants)
Funding Sources
1. * Indicate all sources of support:
External funding
2. * Identify each organization supplying funding for the study:
Funding
Source
Sponsor's
Funding ID
Grants
Office ID Attachments
Pitt
Awardee
Grant
Recipient
National
Institute on
Drug Abuse
1 R21
DA053395-01  
Grant Application
R21 DA053395-
01.pdf
yes
 

View: Pitt SF: Study Team Members
Study Team Members
1. * Identify each person involved in the design, conduct, or reporting of the
research:
Name
Roles
Department/SchoolAffiliation
Involved
in
Consent
QualificationsFinancial
Interest
Brian
Coffman
Co-
investigator
U of Pgh | School
of Medicine |
Psychiatry
Pitt faculty no
has a
doctorate in
Experimental
Psychology
with a
concentration
in
Quantitative
methods. He
has
considerable
experience
and has
written
several
manu...
no
Cynthia
Conklin
Principal
Investigator
U of Pgh | School
of Medicine |
Psychiatry
Pitt faculty yes
is an
Associate
Professor of
Psychiatry
with a
doctorate in
Clinical
Psychology.
She has
considerable
clinical and
research
expertise
with
conditioni...
no
Jordan
Dawson
Secondary
Study
Coordinator
UPMC | Hospital
Divisions | WPIC
UPP/UPMC
staff
yes
Jordan is a
Research
Assistant at
UPMC who
will be
explaining
the consent
with Dr. Tyagi
and running
participants
through the
study
procedures.
no
Ronald
Salkeld
Primary
Study
Coordinator
UPMC | Hospital
Divisions | WPIC
UPP/UPMC
staff
yes
Mr. Salkeld
will be
involved in
recruiting,
consenting,
assessing
study
participants.
He will run
sessions,
manage data
and be
responsible
for the d...
no
Shachi
Tyagi
Co-
investigator
U of Pgh | School
of Medicine |
Medicine
Pitt faculty yes
Dr. Tyagi's
clinical
training in
medicine and
geriatrics,
no
 view all 
 view all 
 view all 

Name
Roles
Department/SchoolAffiliation
Involved
in
Consent
QualificationsFinancial
Interest
combined
with her
basic
research
experience in
urology, has
equipped her
with the
required ...
2. External team member information: (Address all study team members in item
1. above and leave this section blank)
Name
Description
There are no items to display
3. Have you, Cynthia  Conklin, verified that all members of the research team have
the appropriate expertise, credentials, training, and if applicable, child
clearances and/or hospital privileges to perform those research procedures
that are their responsibility as outlined in the IRB application?
*   Yes  No
 view all 

View: Pitt SF: Study Scope 8.1
Study Scope
Check all that apply
1. * Will this study actively recruit any of the following populations?

Adults with impaired decision-making capacity

Children (under the applicable law of the jurisdiction in which the research will
be conducted (<18 years for PA))

Children who are Wards of the State

Employees of the University of Pittsburgh/UPMC

Medical Students of University of Pittsburgh as primary research group

Students of the University of Pittsburgh

Neonates of uncertain viability

Non-viable neonates

Non-English speakers

Nursing home patients in the state of Pennsylvania

Pregnant women

Prisoners
N/A
2. * Will any Waivers be requested?

Waiver/Alteration of Consent

Waiver to Document Consent

Waiver/Alteration of HIPAA

Exception from consent for emergency research
N/A
3. * Will this study involve any of the following?

Specimens

Honest Broker to provide data/specimens

Return of Results to Subjects or Others

Fetal tissue
N/A
4. * Will Protected Health Information be collected?

Pitt medical records

UPMC medical records

Other Institutions’ medical records
N/A
5. * Other Requests?

Deception (if not Exempt, also requires Waiver/Alteration of Consent)

Emergency Use / Single Patient Expanded Access (using FDA Form 3926)
Placebo Arm

Withdraw from usual care

N/A
6. * Determining Scientific Review:
WPIC SRC - Western Psychiatric Institute and Clinic Scientific Review Committee
(this option MUST be picked if from Department of Psychiatry)
7. * Has this study (or substantially similar study) been previously disapproved
by the Pitt IRB or, to your knowledge, by any other IRB?
  Yes  No

Review the HRPO policy, if participating in research at the VA Pittsburgh Healthcare
System or using funding from the VA
8. * Does the study use an approved drug or biologic, use an unapproved drug
or biologic, or use a food or dietary supplement to prevent, diagnose, cure,
treat, or mitigate a disease or condition?
  Yes  No
9. * Does the study evaluate the safety or effectiveness of a device (includes in-
vitro laboratory assays)?
  Yes  No
10. * Is this application being submitted to convert an approved study from
OSIRIS to PittPRO? (Tip Sheet)
  Yes  No
 
11. * Does your research protocol involve the evaluation or use of procedures
that emit ionizing radiation and, after reviewing this HUSC guidance, does your
research protocol require HUSC review? (If yes, upload the HUSC form in the
Local Supporting Documents section). If you are unsure of review
requirement, select yes.
  Yes  No
 

View: Pitt SF: Research Sites
Research Sites 
1. Choose all sites that apply:
University of Pittsburgh
UPMC
* Select the University of Pittsburgh sites where research will be conducted:
Main Campus – Pittsburgh
List university owned off-campus research sites if applicable:
* Select the UPMC sites where research will be conducted:
Western Psychiatric Institute & Clinic
2. Describe the availability of resources and the adequacy of the facilities to
conduct this study:
Western Psychiatric Hospital (WPH) formerly Western Psychiatric Institute and
Clinics (WPIC). A dual entity, WPH is the academic Department of Psychiatry within
the University of Pittsburgh School of Medicine, and also
a psychiatric hospital within the University of Pittsburgh Medical Center (UPMC).
This dual status allows for optimal integration between the academic and clinical
domain. WPH is recognized nationally and internationally as one of the premier
research and treatment centers in the United States. The Department has over 200
primary faculty trained in a mix of disciplines including medicine, psychology, basic
sciences, and social work, who are dedicated to the pursuit of excellence in
research, training and provision of clinical care. Their efforts are supported by
numerous emeritus, secondary, adjunct and volunteer faculty. The intellectual
resources at WPH are enriched by close collaborative ties with numerous other
Departments within the University of Pittsburgh including Psychology, Neuroscience,
Neurology, Kinesiology/Sports Medicine and Radiology. The Department also
maintains active collaborations with many other departments and research
institutions in the U.S. and around the world. The Department of Psychiatry has
been ranked first among all Departments of Psychiatry in the U.S. with regard to
research funding from the National Institutes of Health (NIH) since the mid-1980s.
The University of Pittsburgh ranks among the top ten universities nationwide in the
level of funding from the National Institutes of Health (NIH)
http://www.pitt.edu/research.html). Founded in 1787, it is one of the oldest
institutions of higher education in the United States. As one of the nation's
distinguished comprehensive universities, the resources of the University contribute
to the intellectual, economic, and social enrichment of
Pennsylvania and the nation. The University's mission is to provide high-quality
undergraduate programs; offer superior graduate training; engage in research,
artistic, and scholarly activities that advance learning through
the extension of the frontiers of knowledge and creative endeavor; and cooperate
with industrial and governmental institutions to transfer knowledge in science,
technology, and health care. Due to its central location on the University of
Pittsburgh campus, the Main WPH building is an easily accessed and familiar
location for research participants. Most city bus lines stop within a block of this
building, and campus shuttles stop directly in front of it. For individuals who choose
to drive to research sessions, free parking is easily available in the building’s off-
street garage.

View: Pitt SF: Devices
Devices
1. * List each device in the study that will be evaluated for safety or
effectiveness:
 
Device
Purpose
Type
View NeuroConn
DC-
Stimulator
An IDE application (G150197) was submitted to the FDA on August 14 (recieved by the FDA on September 9, 2015). The
FDA has determined that the proposed study is a nonsignificant risk device study because it does not meet the definition of
a significant risk (SR) device under §812.3(m) of the Investigational Device Exemption (IDE) regulation (21 CFR 812). The
letter from the FDA is attached under the "other attachments section". Overall, there are no significant risks associated with
tES as all risks are very unlikely and minimally serious. Several investigators have examined the safety aspects associated
with transcranial direct current stimulation (tDCS). For example, Iyer et al. (2005), applied 1 and 2 mA anodal, cathodal,
and sham DC stimulation to the left prefrontal cortex for 20 minutes while clinical EEG was recorded. Participants were
encouraged to report any discomfort or subjective sensations while undergoing stimulation. These researchers observed
no aversive EEG abnormalities resulting from DC stimulation, and no participants asked to stop the study or reported any
significant discomfort. Differences in mood between sham and stimulation were assessed using the Visual Analog Mood
Scale (VAMS) that measures subjective reports of anger, anxiety, confusion, energy, fright, happiness, sadness, tension,
and tiredness. The investigators found no measurable effects of stimulation on participants' VAMS scores. Based on their
findings, they conclude that limited exposure to direct current stimulation between 1 and 2 mA is a safe procedure in
healthy participants. In another study conducted by Gandiga, Hummel, and Cohen (2006), tDCS and sham were compared
in healthy volunteers and chronic stroke victims. Discomfort was measured using a 10 point scale, where 1 represented no
discomfort and 10 represented extreme discomfort and pain. These researchers report transient and mild discomfort of
sensations (12 on the 10 point scale) that weren’t significant between sham and stimulation conditions, nor between
healthy volunteers and stroke victims. Safety and tolerability of tES has also been examined in adults with schizophrenia
(Brunellin et al., 2014), as well as childhood onset schizophrenia (Mattai et al., 2011). tES in these studies was wel
ltolerated by participants, and no adverse events were reported. Recently, safety of other forms of tES have been
thoroughly examined. Chaieb et al. (2014) examined assessed safety aspects of Sinusoidal transcranial alternating current
stimulation (tACS) by measuring neuronspecific enolase (NSE) levels, examining electroencephalogram (EEG) traces and
analyzing anatomical data by using magnetic resonance imaging (MRI). tACS was delivered at 5 kHz applied for 10 min at
1 mA intensity over the hand area of the primary motor cortex. No changes were detected in NSE levels, no structural
alterations were observed in the anatomical scans and no pathological changes were found in the EEG recordings.
Additionally, Zaghi et al. (2010) administered various behavioral and neuropsychological tests during tACS. tACS was not
associated with any cognitive adverse effects and had no harmful effects on motor function (Purdue Pegboard Test, Finger
Tapping Test). Moreover, tACS was not associated with pain, mood, or anxiety. DCSTIMULATOR has a Maximum Voltage
Limitation of +/- 20V. The output circuit of the constant current source of the DCSTIMULATOR is equipped with an electrical
fuse which limits the current to 5 mA. Therefore, in any faulty condition and during normal operation, the fuse will become
open circuit if the current exceeds 5 mA by a significant amount. The higher the current exceeds 5 mA the faster it will
become open circuit. This means that it is impossible for the participant to recieve a harmful level of current, even in cases
of equipment malfunction. To avoid thermal discomfort and possible skin damage, the German authority (Bundesanstalt für
Arzneimittel und Medizinprodukte) gives a limit of 0.1 mA/cm² for DC current applications. The largest current density we
will use here is 0.08 mA/cm². We will monitor participant discomfort throughout the administration of tES. If at any point the
participant reports perceived heat, tingling, or itching at the site of the electrodes as 8 or higher on a 10point scale, tES will
be stopped immediately. The Co-I, Coffman, has administered tES to over 250 research participants in previous studies at
the University of New Mexico, with only two adverse events, one of which was due to latex allergy, and the other was due
to small electric shock caused by suboptimal equipment. Only the PI and trained research staff /Co-I's will administer tES
here, and individuals with latex alergy will be excluded. The Neuroconn stimulator used here is robust, so we do not
anticipate this to be a problem here.
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ Evidence of
efficacy across past work, including some from our research team include the following: Past work has shown that brain
stimulation with tDCS during CR further enhances cognitive training, as cognitive effects of tDCS are largely dependent
upon the cognitive faculty being engaged at the time of stimulation (Bradnam, Stinear, Lewis, & Byblow, 2010). We found
enhancement of alerting attention network function measured by the Attention Networks Test, a measure of proactive
cognitive control, more than an hour after anodal tDCS directed at right inferior frontal gyrus (Falcone, Coffman, Clark, &
Parasuraman, 2012). tDCS was paired with complex object detection training, which is thought to engage cognitive control
networks in the brain. Further, tDCS directed at right frontal cortex has been used to increase reactive cognitive control in
the stop-signal task (SST) as evidenced by reaction time and neurophysiological measures obtained with
electroencephalography (EEG)(Jacobson, Ezra, Berger, & Lavidor, 2012). Thus, we plan to use CR + tDCS as a means of
further enhancing cognitive control among smokers with schizophrenia. Three tDCS studies(Boggio et al., 2009; Fregni et
al., 2008; Grundey et al., 2012) in healthy non-quitting smokers (randomized, active vs. sham 1-5 training days) targeting
the dorsolateral prefrontal cortex (DLFPC) found dose dependent reductions in cue-induced craving and smoking behavior.
tDCS has also been shown to significantly enhance the ability of smokers to resist the urge to smoke( Falcone et al., 2016).
Our recent pilot study (N=6) found that weekly group sessions of 30 minutes of mindfulness + tDCS of the right IFG,
followed by 60 minutes of mindfulness + counseling led to a significant 50% reduction in cigarettes per day at the end of
treatment (d=0.50; Witkiewitz et al., 2015). However, CR will be used in this present study, not mindfulness, as it targets
multiple aspects of cognition, and has shown greater efficacy to enhance cognitive deficits among patients with psychosis
(d= >1(Hogarty et al., 2004) vs. d=.41 (Khoury, Lecomte, Gaudiano, & Paquin, 2013)respectively).
__________________________________________________________________________________________________
Boggio, P. S., Liguori, P., Sultani, N., Rezende, L., Fecteau, S., & Fregni, F. (2009). Cumulative priming effects of cortical
stimulation on smoking cue-induced craving. Neuroscience Letters, 463(1), 82–86.
https://doi.org/10.1016/j.neulet.2009.07.041 Bradnam, L. V., Stinear, C. M., Lewis, G. N., & Byblow, W. D. (2010). Task-
dependent modulation of inputs to proximal upper limb following transcranial direct current stimulation of primary motor
cortex. Journal of Neurophysiology, 103(5), 2382–2389. Falcone, B., Coffman, B. A., Clark, V. P., & Parasuraman, R.
(2012). Transcranial direct current stimulation augments perceptual sensitivity and 24-hour retention in a complex threat
detection task. PloS One, 7(4), e34993. Falcone, M., Bernardo, L., Ashare, R. L., Hamilton, R., Faseyitan, O., McKee, S.
A., … Lerman, C. (2016). Transcranial direct current brain stimulation increases ability to resist smoking. Brain Stimulation,
9(2), 191–196. Fregni, F., Liguori, P., Fecteau, S., Nitsche, M. A., Pascual-Leone, A., & Boggio, P. S. (2008). Cortical
stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a
randomized, sham-controlled study. Journal of Clinical Psychiatry, 69(1), 32–40. Grundey, J., Thirugnanasambandam, N.,
Abbrevia

 
Device
Purpose
Type
Kaminsky, K., Drees, A., Skwirba, A. C., Lang, N., … Nitsche, M. A. (2012). Neuroplasticity in cigarette smokers is altered
under withdrawal and partially restituted by nicotine exposition. The Journal of Neuroscience, 32(12), 4156–4162. Hogarty,
G. E., Flesher, S., Ulrich, R., Carter, M., Greenwald, D., Pogue-Geile, M., … others. (2004). Cognitive enhancement
therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior. Archives of General Psychiatry,
61(9), 866–876. Jacobson, L., Ezra, A., Berger, U., & Lavidor, M. (2012). Modulating oscillatory brain activity correlates of
behavioral inhibition using transcranial direct current stimulation. Clinical Neurophysiology, 123(5), 979–984. Khoury, B.,
Lecomte, T., Gaudiano, B. A., & Paquin, K. (2013). Mindfulness interventions for psychosis: A meta-analysis. Schizophrenia
Research, 150(1), 176–184. https://doi.org/10.1016/j.schres.2013.07.055 Witkiewitz K, Kirouac M, Frohe T, Armenta ML,
McCallion E, Roos C, O’Sickey AJ, Brown D, Hunter M, Coffman BA, & Clark VP (2015). (2015). Mindfulness and
Transcranial Direct Current Stimulation as an Intervention for Tobacco Dependence: A Pilot Study.
2. If applicable, identify each investigational device exemption (IDE) number:
IDE Number
IDE Holder
Other Holder
There are no items to display
3. Attach files: (attachments may include justification of risk determination, FDA
correspondence and if the holder of the IDE is a University of Pittsburgh based,
sponsor-investigator, attach both the FDA acknowledgement letter and approval
letter)
 
Document
Category
Date
Modified
Document
History
View FDA Letter is same device.docx(0.02)
Device
Attachment4/22/2021History
View FDA_response_IDE_G150197_Version_0.01_Version_0.01.pdf(0.01)Device
Attachment2/17/2021History
4. * Describe your plan to manage devices so that they will be used only on
subjects and be used only by authorized investigators:
tDCS will be administered by Drs. Conklin and Coffman and Research Coordinator
Mr. Salkeld. Dr. Coffman has applied tDCS in previous research studies to a
combined total of over 250 research subjects and Dr. Conklin and Mr. Salkeld have
been trained by Dr. Coffman. The device will be stored in Dr. Conklin's personal
office in a locked cabinet. Dr. Coffman will also train any additional research staff
over the course of the 2-year study.

View: Pitt SF: Local Site Documents
Click Continue as this page was intentionally left blank.

View: Pitt SF: Recruitment Methods
Recruitment Methods
* Will you be recruiting individuals for participation in this study?
  Yes  No
1. *  Describe who will be recruiting individuals for participation for this study:
The research staff will be recruiting individuals for this research study.
2. * Select all methods to be used for recruitment:
Flyers/Posters or Brochures
Pitt+Me
Telephone scripts
3. * Provide details on your recruitment methods:
Pitt+Me will be utilized to recruit participants through the online portal. Eligible
participants from Pitt+Me will then be contacted by research staff to undergo the
telephone screen for further eligibility determination.
Interested respondents contact the office by telephone or are contacted by us from
the information gained from Pitt+Me and are provided with a brief description of the
study, including its purpose, research procedures, time involved to complete the
study, and participant payments.
Telephone screen: We will ask a few short questions by telephone (screening tool
attached) to determine whether the potential participant is a smoker and initially
eligible to participate for the study and schedule the first visit. Forms for those who
are not eligible will be shredded. No PHI will be collected if participant is found to be
ineligible.
4. * Describe all compensation/incentives offered to participants and timing of
these offers:
Participants will be compensated $20.00 per session, except for the two EEG visits,
which they will be paid $50. At session 4 participants will be paid $20 plus $50
bonus for taking their pictures and continuing onto session 4. At session 10 (the last
in person visit) they will receive $20.00 plus a $50 completion bonus. The
participants will be paid $25.00 per visit for 2 follow-up visits that occur over the
phone. Participants will also be reimbursed for public transit.
5. Recruitment materials: (attach all material to be seen or heard by subjects,
including advertisements and scripts)
 
Document
Category
Date
Modified
Document
History
View AAT_tDCS study flyer
updated phone.doc(0.03)
Recruitment
Materials
3/2/2023 History
View AAT_tDCS Craigslist
Advertisement.docx(0.01)
Recruitment
Materials
3/2/2023 History
View Phone Screen(0.09)
Recruitment
Materials
8/12/2022History

View: Pitt SF: Study Aims
Study Aims
1. * Describe the purpose, specific aims, or objectives and state the hypotheses
to be tested:
Specific aims:
For decades addiction researchers have known that stimuli linked to smoking can
evoke intense craving to smoke, but have failed to discover an effective means of
reducing this persistent source of relapse risk.
Although nicotine replacement therapy reduces "abstinence-induced craving,"
brought on by nicotine withdrawal, it fails to decrease the intense craving evoked by
exposure to smoking-related stimuli, or “cues." Smokers
regularly report that cue-induced craving derails their quit attempts, and research
shows that confrontation with one’s smoking cues in the natural environment
increases the odds of lapsing and/or relapsing. However, past
cue-exposure treatments (CET) to reduce cue reactivity (CR) consistently fail. Three
clear CET methodological weakness likely drive that failure. First, CET traditionally
includes only cues most closely linked to smoking, or proximal cues (e.g., lit
cigarettes, lighters). We have repeatedly found that distal cues (i.e., people and
environments) evoke more robust cue reactivity. A lit cigarette will make most
smokers crave, but one’s smoking
friends (people cue) or car on the way to work (environment cue) evoke much
stronger craving and increase subsequent smoking. Reactivity is further enhanced
when cues are combined. Yet, no CET has ever included
these personal cues. Second, CET involves passive cue exposure. Smokers are
repeatedly exposed to proximal cues while refraining from smoking until their CR
diminishes. Although rooted in animal drug extinction studies, this method does not
translate well to the cue-rich experience of human smokers or prepare them to
encounter the panoply of smoking triggers in their daily lives. Thus, CET’s failure is
not surprising, and it will continue to fail until personal cues are targeted and
smokers are trained to actively reject their well engrained approach tendency to
such cues. The Approach/Avoidance task (AAT), is an active behavioral method of
cue re-training involving pushing away (rejecting) stimuli during exposure. This
method engages the dorsolateral prefrontal cortex (PFC), a region of the brain
linked to cognitive control over drug use decisions and motivations, making it an
excellent candidate for our third CET improvement; namely brain stimulation to
bolster cue re-training. Transcranial Direct Current Stimulation (tDCS) is a non-
invasive means of increasing excitability in cortical brain regions. tDCS targeting the
PFC has shown encouraging results in reducing smoking CR as a standalone
treatment; however, studies of other disorders suggest greater efficacy when it is
combined with a behavioral task that engages the same brain region being
stimulated. Thus, combining PFC-targeted tDCS with AAT cue
re-training, should provide a synergistically robust means of reducing smokers’ CR
to personal smoking cues. We hypothesize that AAT and tDCS applied to the dlPFC
will each attenuate smokers’ reactivity to personal combined smoking cues, indexed
as cue-induced craving, smoking topography, and attentional bias (behavioral
Stroop and neurophysiological EEG), and that the combination of AAT+tDCS will
prove
synergistically effective. We will also examine the impact of these methods on quit
intention and confidence in quitting and reduction in cigarettes per day (cig/day)
from pre-post training, and at 2 follow ups. We will explore
sex and other individual differences as moderators of this new CET’s efficacy. Eighty
high treatment-interest smokers will receive one of four training conditions:
AAT+tDCS, AAT+sham tDCS, Active control (AC)+ tDCS, or AC+sham tDCS.
Baseline assessment and re-test of reactivity variables will occur following 5
AAT/tDCS sessions of personal combined-cue exposure, with follow-up
assessments of cig/day, intent and confidence to quit at 1 week and 1-month post-
training.
Our specific goals are:
Aim 1: Determine the effectiveness of AAT and tDCS to attenuate cue-induced

craving and attentional bias to personal smoking stimuli. AAT, tDCS, and combined
AAT + tDCS will each lead to greater
reductions in pre-post training cue-induced craving and improved behavioral
(quicker reaction time) and neurophysiological (lower P300 ERP) measures of
attentional bias for smoking cues over the control condition.
Aim 2: Determine the effectiveness of AAT and tDCS to reduce cue-provoked
smoking behavior and daily smoking, and to increase intent and confidence to quit.
AAT, tDCS, and combined AAT + tDCS will
each lead to greater pre-post-training reductions in smoking topography measures
(latency to light & puff volume) assessed during cue exposure, as well as reduced
cigs/day and increased confidence and intent to
quit from pre-training to post-training and 1-week & 1-month follow-up over the
control condition.
Aim 3: Examine if changes in reactivity to smoking-related cues (Aim 1) are
associated with posttraining reductions in smoking topography and/or cig/day and
increases in intent and confidence to quit. (Aim 2). Reduced craving and attentional
bias to smoking stimuli across all groups will be associated with reductions in
smoking topography post-training, as well as post-training and follow-up changes in
cigs/day and confidence and intent to quit Secondary Aim: Explore sex and other
individual differences as moderators of outcome measures to explore who might
benefit most from AAT and tDCS methods.
There have been few recent innovative approaches for alleviating cue-induced
craving to smoke. AAT and tDCS are two promising methods to newly apply to this
endeavor. Although this exploratory work is not fully powered to detect significant
interaction effects of AAT and tDCS, we will examine the size of the interaction to
inform potential efficacy trials of combined AAT + tDCS vs the individual therapies
alone. The results here will thus guide a future RCT of novel CET methodology
within a cessation trial aimed at helping more smokers stay quit.
2. * Describe the relevant prior experience and gaps in current knowledge
including preliminary data. Provide for the scientific or scholarly background
for, rationale for, and significance of the research based on existing literature
and how it will add to existing knowledge:
SIGNIFICANCE
Obstacles to quitting smoking. Smoking accounts for upwards of 400,000 annual
deaths in the U.S. alone.1 Most current smokers report a desire to quit, but
cessation rates with any treatment rarely exceed 30%.
Cessation failure is often attributed to abstinence-induced craving during nicotine
withdrawal. However, studies of nicotine replacement therapy (NRT) show that even
when smokers are given nicotine at levels comparable to smoking, over 70% still
relapse. Thus factors other than the pharmacological effects of nicotine clearly play
a crucial role in smoking behavior. One such factor, frequently studied but not well
understood, is reactivity to smoking cues. Considerable research demonstrates that
stimuli present during smoking gain associative properties, which when later
encountered in the absence of drug reinforcement (e.g., nicotine) induce robust urge
to smoke (i.e. cue-induced craving). Recent cue reactivity (CR) studies show that
cue-induced craving predicts immediate subsequent smoking, as well as speed and
volume of actual smoking. Unlike abstinence based craving, cue-induced craving
and smoking is not reduced with nicotine replacement and can continue long after
physiological nicotine withdrawal abates. Moreover, smokers report that smoking-
related cues are a vital aspect of their difficulty or inability to stay quit,15 making it
even more unfortunate that, to date, no efficacious treatment exists to attenuate this
unrelenting source of relapse risk.
New methods to reduce cue-induced reactivity. If reactivity to smoking-related cues
is a factor driving craving and inhibiting a smoker's ability to stay quit, then, as many
researcher purport, extinguishing CR through
repeated unreinforced exposure to smoking cues (i.e., cue exposure treatment;
CET) should increase cessation success. However, traditional CET-based
treatments have consistently failed to attenuate CR or increase smoking cessation
rates. To improve CET, researchers have suggested that, given the link between
cognition, craving, and relapse, cue-based treatments should focus on training

cognitive control to reduce cue reactivity. Moreover, empirical evaluation of past CET
studies by us and others provide additional direction on promising ways to improve
CET. Thus, we have identified three key reasons for past CET failure, as well as
three techniques, exploiting new technology, to remedy CET.
1) Targeting just proximal cues is not adequate. Regardless of drug or cue
presentation mode (e.g., pictorial, in vivo), the majority of CR studies and CETs have
targeted smokers’ reactivity to proximal cues, cues most closely linked to actual drug
administration (e.g., cigarettes, lighter). However, our research clearly shows that
distal stimuli present during smoking also gain associative control over craving.
Specifically, the
actual environments and people in a smoker's life, through repeated pairing with
smoking, can alone, in the absence of proximal cues, trigger strong cue-induced
craving, and immediate smoking. When exposed to pictures of their personal
smoking and nonsmoking environments, as well as standard smoking and
nonsmoking environments, personalized smoking environments significantly
enhanced smokers’ self-reported craving over all other cue combinations. In another
study, viewing personal smoking environments increased BOLD signal in multiple
brain regions associated with craving to smoke, corresponding to higher self-report
cue-induced craving (F(2,180)=18.32, p<.0001). Yet another study using pictures of
smokers’ friends and acquaintances around whom they do or do not smoke revealed
both enhanced craving to pictures of smoking related people, and a significant
inhibitory response on craving to people around whom they do not smoke. Most
recently, we found that combining proximal and personal environment smoking cues,
led to the greatest increase in cue-induced craving and smoking topography
(indexed as latency to light, # of puffs, and puff volume during cue exposure). Thus,
CET incorporating only proximal cues and standard, not personal, stimuli fails to
capture the multitude of cues that bring about smokers’ strongest cue-induced
craving and actual smoking behavior. As noted by even the earliest researchers of
extinction training, in order to adequately
reduce reactivity to cues, the cues targeted must be those that evoke the strongest
reactivity. Our past work suggests that combining multiple personalized cue types
lead to the greatest increases in cue-induced craving and smoking. These cues
must be targeted in any treatment adjunct aimed at attenuating smokers’ cue
reactivity.
2) New learning requires more than just unreinforced exposure. Most CETs involve
passive exposure to cues while repeatedly refraining from smoking. However, active
re-training may prove much more effective in reducing CR. The approach/avoidance
task (AAT) specifically targets attentional biases toward visual stimuli. The AAT, by
which smokers actively push away or pull in pictorial stimuli with a joystick, can
reduce reactivity to smoking stimuli, specifically attentional bias, as well as daily
smoking. This
approach/avoidance retraining method is based on cognitive embodiment theories,
which have demonstrated the effects of motor actions on cognition. Arm movements
during AAT activate motivational systems in the brain: Arm flexion (approach
behavior) activates a reward motivation system, whereas arm extension (avoidance
behavior) activates a motivational system involved in processing possible threats.
Avoidance behaviors call for vigilance and controlled action. Because of this
repeated association, avoidance behaviors may lead to greater recruitment of
resources. Repeated exposure to smoking-related stimuli while smoking strengthens
appetitive responses, which leads to the development of automatic approach
tendencies, most often indexed as attentional
bias, to smoking-related cues. Smokers demonstrate a strong approach bias toward
smoking stimuli that is not present in ex-smokers, a bias which has been implicated
in the maintenance of smoking behavior and
likelihood of relapse. Neurologically, regulated avoidance responses during AAT
(e.g., smokers avoiding smoking stimuli) leads to stronger activation in the
dorsolateral prefrontal cortex (DLPFC) indexed as lower
deoxygenated hemoglobin (HHb).37 Thus, AAT re-training may alter implicit
attitudes toward smoking by dynamically engaging DLPFC and increasing cognitive
control during exposure to smoking-related cues.38
Further, although AAT has not been tested as a method of reducing cue-induced

craving, it has been shown reduce attentional bias to smoking stimuli and decrease
daily smoking. Studies that included a follow-up
found sustained smoking reduction at 1-month and 3-months post-AAT training.
Thus, multiple exposures that involve active re-training of motor responses to cues
(executing an avoidance response by pushing smoking
stimuli away and an approach response by pulling in stimuli that inhibit craving)
should activate the PFC and result in cognitive-control-mediated changes in CR
(reduced craving and smoking). This more active and robust extinction training
should better generalize to decision making when faced with personal smoking
cues.
3) Non-invasive brain stimulation to bolster new learning. Transcranial Direct Current
Stimulation (tDCS), is a safe, non-invasive method of brain stimulation that can
enhance cortical excitability and help attenuate cue-induced craving. Animal studies
show clear neurophysiological effects of tDCS, where anodal tDCS enhances and
cathodal tDCS reduces neuronal excitability. Human pharmacological studies
confirm these results. Thus, tDCS has become increasingly popular in clinical and
neurocognitive research with known neurobiological targets, showing promising
efficacy in reducing drug craving, auditory hallucinations in schizophrenia,
depression, Parkinson’s disease, stroke, and cognitive enhancement in healthy
subjects. tDCS of the prefrontal cortex (PFC) reduces cue-induced craving and daily
smoking by improving decision-making and cognitive control. Most important to
note, although effective as a standalone treatment for reducing cue-induced craving,
the effects of tDCS are greatly enhanced when stimulation is paired with tasks that
engage the brain processes that underlie the targeted behavior. Thus, we purport
that AAT during cue exposure, which engages the dlPFC, is a prime candidate for
augmentation with PFC-targeted tDCS. Enhanced excitability in PFC during AAT
should improve ability to dynamically recruit
cognitive control systems during avoidance behaviors, aiding in the retraining of
smoking-related cue valence. Thus, effects of AAT+tDCS on CR to smoking cues
and behavior should be synergistically more effective.
The decision to target PFC comes from its repeated implication as a key seat of
cognitive control over craving, particularly cue-induced raving. Although several
brain regions, notably the ventral striatum (VS),obitofrontal cortex (OFC), and
anterior cingulate cortex (AAC) are
activated during exposure to drug cues, particularly during cost/value
assessments, the PFC is hypothesized to combine these
valuations with other information, such as drug context/availability and prior
outcomes. Imaging studies reveal that VS activation during cue exposure increases
craving, and activation of the PFC during cue exposure downregulates the VS
resulting in attenuation of craving Studies of PFC-targeted tDCS further support this
link. In three studies of non-quitting smokers (randomized to active or sham for 1-5
days), stimulation of dorsolateral PFC (dlFPC) led to dose-dependent reductions in
cue-induced craving and daily smoking (i.e. effectiveness increased with number of
sessions, 30% fewer cigs/day). tDCS also enhances ability to resist the urge to
smoke. In our recent study, weekly group sessions of 30min of Mindfulness + tDCS
(targeting rPFC), followed by 60min of Mindfulness + counseling led to a significant
50% reduction in cig/day at the end of treatment (d=0.50), with individuals reporting
greater control over craving after treatment. Given our focus on attenuating cue
reactivity here, we will include AAT, not mindfulness. In AAT, avoidance behaviors
have been shown to signal the recruitment of cognitive control centers in dlPFC, a
likely component in its effectiveness. Thus, enhancement of dlPFC excitability with
tDCS, and retraining approach/avoid biases to one’s most salient personal smoking
cues, are both promising methods that target PFC activation, and their combination
may further enhance reductions in smokers’ cue reactivity and other outcome
measures. Of note: Studies have examined left or right dlPFC as a stimulation
target, with one study comparing both, with no difference as a function of
lateralization. We propose right side stimulation based on our past success targeting
right PFC. tDCS, Attention, and Craving in alcohol and food: Aside from the smoking
studies reviewed above, a few
studies on the impact of tDCS on attentional bias and craving for food and alcohol
cues are worth noting. These studies found largely null results, albeit with methods

starkly different than those proposed here. Further, CR
varies by drug/substance of choice, with reactivity to alcohol and food cues being
notably less robust and less affected by the same manipulations as smoking. One
alcohol study, found no effect of 1 weekly tDCS session
for 4 weeks on attentional bias and craving in college drinkers, and three others,
also using limited tDCS, showed no changes in attentional bias, but revealed
craving reductions. One food study found null results after 1 tDCS + cognitive
modification session to reduce chocolate craving. Smoking tDCS studies suggest
that multiple sessions closely spaced increase efficacy, thus we propose 5 closely
spaced sessions of tDCS during personal smoking cue exposure. No studies have
used personal cues from participants lives, pre-post cue reactivity assessment of
craving and behavior, or highly dependent individuals. No studies, including
smoking, have examined combined tDCS + AAT. Thus, although the proposed work
is high risk, past null findings across other substances using generic cues and
focusing on attentional bias do not predict null effects here, rather extensive past
work on each of our included components and strong theory behind combining tDCS
+ AAT suggest potential for high reward. Assessing the impact of novel CET on
smoking-related outcome measures. Attentional Bias. Smokers demonstrate
selective attention to smoking-related stimuli. and delayed reaction time (RT) during
exposure to smoking cues. They are slower than controls to color-name smoking-
related words in a modified Stroop task, which combines common words with
intermittent presentation of smoking-related words. Smokers maintain their gaze on
smoking stimuli longer than neutral stimuli, and show increased P300 response to
smoking-related cues. The smoking-cue P300 is thought to reflect attentional and
motivational state of smokers when cues prime smokers’ urge to smoke. According
to incentive-sensitization theory, these biases likely emerge from the motivational
and attention-grabbing properties of smoking cues, which gain salience after
repeated pairing with smoking. This causes sensitization of dopamine
neurotransmission in the striatum increasing the salience of the stimuli long-term
and resulting in greater allocation of attentional resources (attentional bias) and
increases in
craving. Abstinent smokers with greater attentional bias to smoking stimuli are more
likely to relapse, reducing this response may aid cessation. In our pilot studies, we
assessed attentional bias behaviorally and using EEG,
in a forced-choice RT task and found a decreased RT difference between smoking
and neutral stimuli of 60% (p<0.05) following tDCS. We also show that tDCS of right
dlPFC using the same montage proposed here
(N=8) reduced the P300 difference between smoking and nonsmoking images
compared to sham tDCS (N=8) in smokers with long-term/chronic schizophrenia
(Figure 2). In the proposed study, we anticipate that AAT and
tDCS training will reduce approach bias indexed as decreased RT and P300
amplitude difference between smoking and neutral images from baseline to re-test
during a modified smoking Stroop task. Cue-Induced Craving and Smoking. As
noted above, smokers report that smoking cues are a major obstacle to quitting and
multiple studies have demonstrated robust cue-induced craving,cue-induced
smoking behavior, and a strong link between the two. Our procedures to personalize
cues, present them in combination, and assess smokers’ self-report and behavioral
CR creates an ideal environment to develop and test novel CET methodology.
Although the combination of AAT + tDCS has not been assessed for reduction of
cue-induced reactivity (craving or smoking topography), research on these two
procedures independently have
examined AAT effects on attentional bias and daily smoking, and tDCS effects on
cue-provoked craving and daily smoking, with mixed but largely positive effects.
Given that tDCS is known to be more effective when it is
used while engaging the neural processes targeted for change, we anticipate that
combining AAT + tDCS during cue exposure may further enhance reduction in cue-
induced craving and smoking topography (latency & puff volume) to combined
personal smoking cues (proximal, environment, and people) as measured at
baseline and re-testing after 5 sessions of training. Daily smoking (cigs/day) and
Intent and Confidence to quit. Both AAT and tDCS have independently shown
efficacy in reducing daily smoking among non-quitting smokers with high treatment

interest. We anticipate similar results here, as well as reductions in cue-induced
craving and smoking topography. Given that tDCS should enhance AAT learning, we
also anticipate that AAT+tDCS may further reduce in these measures. We will also
examine potential increases in Intent and Confidence to quit, the former shown to
increase with AAT training and both previously associated with quit initiation and
ability to abstain. These three measures will be assessed pre-post training and, to
examine more prolonged effects, at 1-week and 1-month post-training. Sex and
individual differences. Although past cue reactivity, AAT, and tDCS work has not
revealed sex differences across outcome variables, we will specifically recruit equal
numbers of male and female smokers to determine if sex, as well as other individual
differences (e.g., age, FTND, years smoking) moderate AAT/tDCS efficacy on our
more comprehensive set of outcomes, and thereby offer new information about for
whom our novel methods may work best as a smoking treatment.
INNOVATION.
The proposed study will be the first active and sham-controlled test of AATand tDCS
during personalized multi-cue exposure to attenuate several indices of smoking-
related cue reactivity and behavior. Several aspects of this
exploratory/developmental study are highly innovative. 1) AAT: Although
recommended, AAT effects on cue-induced craving have surprisingly not been
formally studied. Past AAT smoking cue studies reveal promising effects for AAT on
measures of daily smoking and
attentional bias, but have not examined cue-induced craving. Likewise, no AAT
studies have included neuropsychological measurement of attentional bias (EEG) or
changes in cue-induced smoking topography
(latency to light, puff volume). 2) tDCS: tDCS applied to the dlPFC can reduce
reactivity to proximal smoking cues (cigarettes, lighters) and can reduce daily
smoking in non-quitting smokers. This will be the first assessment of dlPCF-targeted
tDCS effects on smoking attentional bias (Stroop and EEG), craving to personal
cues, and cue-induced smoking topography. 3) Combining AAT + tDCS: No studies
have examined combined AAT+tDCS on smoking CR, attentional measures or
smoking behavior. Given that tDCS is known to be more effective when used while
engaging the faculty targeted for change we anticipate combined AAT+ tDCS
targeting dlPFC will have a synergistic effect on our comprehensive index of
reactivity measures to combined personal smoking cues, as well as daily smoking
and intent and confidence to quit. Our 2 x 2 design allows us to examine AAT and
tDCS independently across multiple new outcome variables, as well as the
combined impact of these two methods. 4) Multiple Personal Cues Exposure: CET
should be most effective when cues evoke smokers’ strongest reactivity and capture
key elements of the original contexts of learning. The proposed study will be the first
to incorporate all cue types (people, places and objects) during CET to target
numerous specific stimuli that trigger each smoker's strongest urges to smoke.
Multiple exposures to real world cue re-creations should enhance the
generalizability of training outside of sessions, a purported shortcoming of past
CETs, and allow us to capture smokers’ most salient cues without the inherent
difficulties of conducting real world exposures.
 

View: Pitt SF: Study Design
Study Design
1. Total number of subjects to be enrolled at this site (enter -1 for chart reviews,
banking, registries):
160
2. Describe and explain the study design:
Study Design and Procedures. Eighty (male=40, female=40) high treatment-interest
daily smokers age 26-55 will be recruited from the local Pittsburgh community. As
noted, past work has not revealed sex differences in CR, AAT, or tDCS training
outcomes with smokers, but we will examine sex differences here. Participants will
be screened via telephone interview, and again in person, for multiple measures
including level of quit interest, assessed by asking subjects if they intend to quit
smoking in the next 1, 3, 6, 12 months, longer, or never. Using a 2 x 2 design we will
examine AAT (AAT, active control [AC]) X tDCS (active, sham) to reduce cue-
induced craving and smoking topography, and attenuate behavioral and
neurophysiological measures of attentional bias to combined personal smoking
cues. We will also determine the impact of this novel CET methodology on daily
smoking, intent and confidence to quit, and explore sex and other individual
differences in the efficacy. Eligible participants will come to the laboratory and
complete informed consent and further screening, including vision screening for
sensory deficits that may affect cue reactivity and/or EEG testing, re-assessment of
treatment interest and completion of forms. Participants will also undergo the semi-
structured interview to identify the places of which to take pictures, and complete
camera practice. After initial screening, participants will be randomized to one of the
4 groups (stratified by sex & age). Dropouts will be replaced but examined by
AAT/tDCS group to assess tolerability. Groups include: 1) AAT + active (2.0 mA)
tDCS, 2) AAT + sham (0.01 mA), 3) active control (AC) + active tDCS, or 4) AC +
sham. Participants will participate in AAT/tDCS intervention sessions for 5 days over
3 weeks, but the over all study will be 10 visits total similar to our
tDCS/schizophrenia study (DA0417742), and that by Mattai et al. Cue-induced
craving, smoking topography, and attentional bias (reaction time & ERPs), as well as
cigs/day intent to quit90 and confidence in quitting91 will be assessed at Week 1
Baseline sessions 1 & 2 and Re-test sessions 9 & 10 during Week 3. Cigs/day,
intent and confidence to quit will be re-assessed during follow-up phone calls 1-
week and 1-month post-training
3. Describe the primary and secondary study endpoints:
Primary:
1.Cue Reactivity to personal cues, baseline to post treatment. Attenuation of
reactivity to smoking-related cues will be a primary outcome variables for this study.
The measures include self-reported cue induced craving, smoking topography
measures of latency to light and puff volume, as well as attentional bias measures of
reaction time and ERPs to smoking stimuli.
2. Daily Smoking, baseline to post-training and follow up. To examine the impact of
AAT + tDCS on daily smoking we will assess each participant's pre- and post-
training daily smoking, indexed as cigs/day.We will then re-assess average cigs/per
day via follow-up phone call assessments at 2 time points (1-week and 1-month post
training).
3. Intent and confidence to quit, Baseline to Post-treatment and follow-up.
Participant ratings of Intent to Quit and Confidence to quit will be assessed at
baseline and end of treatment to determine if AAT/ tDCS training has a
measurable impact on these smoking cessation related measures. To examine
prolonged effects of AAT / tDCS, they we be re-assessed at 1-week and 1-month
post-training via follow-up phone call assessments.
Secondary:
Sex and Individual Differences, Baseline to Post-training and follow up. Secondary

analyses will probe whether sex and other individual difference variables
(e.g.,FTND, age) moderate the effect of experimental group on
cue-induced craving and attentional bias, smoking topography, daily cig/day and
intent & confidence to quit.
4. Provide a description of the following study timelines:
Duration of an individual subject's active participation:
Approx 2 months
Duration anticipated to enroll all subjects:
Approx 19 months
Estimated date for the investigator to complete this study (complete primary
analyses): 
4/28/2023
5. List the inclusion criteria:
Inclusion Criteria:
-Between the ages of 22 & 65
-Ability to provide written informed consent
-Smoke ≥ 5 cigarettes per day
-Expired breath CO ≥ 5 ppm at screening
-Ability to attend 10 sessions over a 3-week period, and complete 2 follow-up phone
assessments
6. List the exclusion criteria:
Exclusion Criteria:
-Implanted cardiac or brain medical devices
-History of epilepsy or current seizure disorder
-History of brain surgery or skull fracture
-History of a head trauma (losing consciousness >10 min and/or problems with
speech or movement because of head injury)
-Latex allergy
-Scalp irritation
-History of diabetes that caused loss of consciousness (>10 min) or weakness in
your arms or legs
-History of ECT (electroconvulsive therapy) in the last 5 years
-Current use of dextromethorphan
-Diagnosed with or undergone treatment for alcohol or substance dependence past
3 months
-Uncorrected vision deficit
-Colorblindness
-Use of tobacco products other than commercially available cigarettes
7. Will children or any gender, racial or ethnic subgroups be explicitly excluded
from participation?
  Yes  No
* Identify the subgroups and provide a justification: 
Children, individuals defined as under the age of 18, will not be included as it is
illegal to sell cigarettes to minors in Pennsylvania. The safety and efficacy of tDCS
has not been tested in pediatric smokers, and standard doses have not been
established.
8. Describe the power analysis used and cite your method of statistical analysis.
If a power analysis is not possible, thoroughly justify the sample size required
for the study, including appropriate literature citation (alternatively provide
page reference in attached protocol):
Statistical design and power
This study uses a 2 x 2 AAT (AAT, active control[AC]) x tDCS (tDCS, sham tDCS)
design to assess prepost training changes in cue-induced craving and smoking

topography (latency to light and puff volume during cue exposure) and attentional
bias (reaction time and ERPs) to smoking-related cues, as well as daily smoking
(cigarettes per day) and confidence and intent to quit. The primary analyses (Aims 1
and 2) will be evaluated via repeated measures multivariate analysis of covariance
(RM-ANCOVA) and will test the main effects of AAT, tDCS, and their interaction on
measures of craving, reaction time, P300 amplitude, controlling for baseline levels
as covariates (Aim 1). This process will be repeated for Aim 2, where MANCOVA will
test effects on latency to smoke, total puff volume, and cigs/day. An additional 2x2x3
repeated measures (RM-) MANCOVA will test group differences in cig/day and intent
& confidence to quit
across time points (post-training, 1-week, and 1-month). For Aim 3, regression
analysis will be used to examine if attenuation of cue-induced craving and
attentional bias measures predict reductions in smoking
topography and daily smoking and elevations in intention to quit and confidence to
quit, while controlling for baseline levels of these variables. Exploratory analyses will
probe whether sex and other individual differences (e.g., age, FTND) moderate the
effects of AAT/tDCS training on all outcome variables.
Power is based on n=20 high treatment-interest smokers per group, with 4
experimental groups. Drop outs
in this experimental study will be replaced. We will examine differential group
dropout to assess tolerability of methods. Limited past work leads us to constrain
our power analysis to AAT and/or tDCS for each variable, but we expect the
synergistic effects of combined AAT + tDCS to be even greater, making these power
analyses conservative. However, this exploratory work is not fully powered to detect
significant interaction effects. Aim 1. Craving and Attentional bias. Assuming a
Cohen’s d effect size (ES) of 1.02- 1.57 based on prior literature, a multivariate α =
.05, and an R2 of .3 from other covariates in the model, we expect to have greater
than 0.99 power to detect main effects of tDCS on cue-induced craving. Boggio et
al.41 found an ES of d=1.13 for reduction in cue-induced craving via tDCS. Our pilot
P300 EEG data from our current study in smokers with schizophrenia shows ES of
d=1.3. AAT work indicates post-training
attentional approach bias reductions to smoking cues of d=1.2629, thus we expect
greater than .80 power to detect changes in attentional bias. Aim 2. Smoking
topography and cig/day. Based on our past cue studies, smoking topography to
multiple cues are of similar magnitude to cue-induced craving (d=.90). Further, past
tDCS studies of daily smoking outcome show an ES of 0.58100. Thus, with a
multivariate of α=.05, 20 subjects per group, and an R2 of .3, we expect greater than
0.84 power to detect an effect of tDCS on smoking behavior in both the MANCOVA
assessing immediate effects on smoking behavior and the RM-MANCOVA
assessing longitudinal effects on cig/day and intent & confidence to quit. Again,
tDCS
+ AAT should enhance effects. Aim 3. Smoking prediction. Assuming α=0.17
(conservative adjustment for 3 outcome variables) and controlling for other variables
contributing an R2 of .3, we will have power greater than .99 to detect an R2 of
0.2422 or larger, in the model predicting smoking topography and cig/day from cue-
induced craving and attentional bias change scores.

View: Pitt SF: Research Activities
Research Activities
1. * Provide a detailed description of all research activities (including screening
and follow-up procedures) that will be performed for the purpose of this
research study. This description of activities should be complete and of
sufficient detail to permit an assessment of associated risks.
The PI, Co-I's and Research Coordinators will be responsible for carrying out all the
research activities.
Visit 1: During this visit we will explain the study and all its procedures with the
potential participant. If he/she agrees to participate and signs the consent we will
move forward with visit 1 procedures. A carbon monoxide (CO) level will be
measured by giving a breath sample using our breath CO monitor. If the participants
CO level is below 8 ppm they will not be able to continue with the study and will be
paid for today’s visit and excused from the study.
The participant will complete the following forms:
•Smoking History: This form will ask questions about the participant and their
smoking history and will also assess the participant's level of nicotine dependence.
•Quit Interest: This is a questionnaire for evaluating the participant's interest in
quitting smoking.
•Intent to Quit: This measures the participant's degree of intention to quit smoking.
•Confidence in Quitting: This questionnaire assesses the participant's confidence in
quitting smoking.
Next, we will identify personal smoking and non-smoking cues of places. The
participant will go through a brief interview during which we will identify places in
which they regularly smoke or do not smoke. We will lend them a camera and teach
them how to take pictures before the next visit. The participant will take pictures of
their top 4 places that are ‘smoking cues’ and 4 places ‘non-smoking cues’ from
various angles. We ask that they don’t take pictures of people (passers-by or any
other friends/family in the pictures) or personal identifiers (license plates, street
names, etc.) to protect privacy. The participant will bring the camera containing the
pictures back with them to the second session during which time they will be
checked to make sure they took the correct pictures identified and that they will work
for the presentation program used in the study. If they do not the participant will be
instructed to take more pictures to bring with them at the next scheduled visit.
Participants will be advised that they must not send any images that are considered
distasteful, obscene, implicate legal action.
The participant will return the lent camera containing the pictures when they come
back for the next study visit. We will also have the participant complete a brief vision
test during this visit. They will stand 10 feet from an eye chart, identify and read out
loud the line they can see most comfortably.
•The participant will be randomly assigned to one of four groups:
1. AAT + tDCS
2. AAT + sham tDCS
3. AC + tDCS
4. AC + sham tDCS
The components of these groups are defined as:
•Approach/Avoidance Task (AAT): The participant will use a joystick to push and pull
images in different directions on a computer screen.
•Transcranial Direct Current Stimulation (tDCS): is used to slightly change the way
the brain works for a short time. One wet, thin sponge is placed on the participants
head and another wet thin sponge is placed on their arm and connected to
electrodes which will deliver a very weak electrical current. Before stimulation, their
head and arm will be checked for any redness, irritation, or recent shaving of the
head. If any of these are seen, we will exclude them from the study. Some
participants may feel a slight painless tingling as the current begins, but the tingling
should go away after a short time. tDCS will be given at 2.0 mA and stimulate the

dorsolateral PFC (dlFPC) the sham tDCS will be given at 0.01 mA. We will ask the
participant at the beginning of and throughout the stimulation to report how much
tingling they are feeling on a scale of 1 being “not at all” and 10 being “extreme”. If at
any point they are experiencing extreme discomfort, we will end the stimulation.
•Active Control (AC): The participant will assess the orientation of a picture and
indicate it with a key press.
•Sham tDCS: Two wet, thin sponges are placed on the participants head and arm
and the sponges will be connected to electrodes just as the actual tDCS but they will
not deliver any electrical current.
Visits 2 and 9: During this visit the participant will have an attentional bias
assessment while undergoing an electroencephalography (EEG).
•Attentional-Bias: You will be seated in front of a computer with a four-button color
response box. Four different word lists of 15 words each will be presented in a
random order with no repeats. For each trial, a cross appears in the center of the
screen followed by one word from the list in one of four colors. You will press the
button that matches the color in which the word appears.
•EEG: The EEG allows us to measure electrical activity of the participants brain. A
cap containing sensors will be placed on their head. In addition, sensors will be
placed behind the ears, and on the tip of the nose. Gel will be inserted into the cap
to connect the sensors to the scalp. The participant will not feel any sensations from
these electrodes. While wearing the cap, they will complete the attentional bias
training. Afterwards, we will clean as much of the gel from their scalp as possible.
•Cue-reactivity: Cue reactivity involves viewing pictures of the participants personal
smoking-related and non-smoking-related pictures and rating how they felt while
viewing those pictures. The pictures and the ratings are presented on a computer
and some pictures will be projected on the wall.
Visits 3 and 10: During these visits the participant will complete cue-reactivity to their
personal smoking and non-smoking cues and smoke cigarettes using a special
cigarette holder that will measure how they smoke their cigarette. The participant will
be given special instructions on how to light the cigarette and place it into the holder
before they smoke. They will be seated comfortably in front of a large computer
monitor and view 12 picture trials. Each picture trial will be followed by post-trial
ratings. After all the picture trials, a screen will appear informing them that when
pictures begin to appear again they may smoke (using the cigarette holder) as much
or little as they like, or not smoke at all, it is up to them and watch the pictures. At
any point while viewing these pictures they may start or stop smoking.
Visits 4-8: During these visits the participant will go through cue-reactivity while
either doing AAT while receiving tDCS (Group 1), doing AAT while receiving sham
tDCS (Group 2), doing AC while receiving tDCS (Group 3), or doing AC while
receiving sham tDCS (Group 4). The participant will not specifically know which
group they are in.
Follow-up: We will call the participants at 1-week and 1-month after visit 10 and ask
them how many cigarettes per day they are smoking and ask them the intent and
confidence to quit questionnaires.
2. Upload a copy of all materials used to collect data about subjects: (Attach all
surveys, interview/focus group scripts, and data collection forms except for
case report forms, SCID or KSADS):
 
Document
Category
Date
Modified
Document
History
View Environment Listing Sheet(2)
Data
Collection
3/2/2023
History
View AAT_tDCS Study Calendar
Handout.docx(0.02)
Data
Collection
5/23/2022
History
View BIDR-IM.doc(0.01)
Data
Collection
5/17/2022
History

 
Document
Category
Date
Modified
Document
History
View Smoking Environment Places Interview
Sheet.doc(0.01)
Data
Collection
5/17/2022
History
View Non Smoking Environment Places
Interview Sheet.doc(0.01)
Data
Collection
5/17/2022
History
View Smoking History Form(0.01)
Data
Collection
3/15/2021
History
View Intent Ladder(0.01)
Data
Collection
3/15/2021
History
View Intent to Quit(0.01)
Data
Collection
3/15/2021
History
3. * Will blood samples be obtained for research purposes?
  Yes  No
 

View: Pitt SF: Consent Process
Consent Process
Enter N/A in response to the following questions if a Waiver of Consent is requested for all
research activities or if no subjects are being enrolled.
1. * Indicate where the consent process will take place and at what point
consent will be obtained:
Informed consent will take place at Session 1 in Dr. Conklin's laboratory on the 16th
floor of the Department of Psychiatry at Western Psychiatric Hospital after the
subject has been telephone screened. The informed consent process is a concerted
effort between Dr. Tyagi and either Dr. Conklin, and/or the research coordinator. The
potential participant is addressed in a private room and the most current IRB-
approved informed consent form is reviewed point by point with either Dr. Conklin,
and/or the research coordinator. All aspects of the study are explained, including but
not limited to the nature of the study, its purpose and associated procedures, the
expected duration, and the potential risks of participation. In addition, the subject is
informed about the right to withdraw from the study at any time without any
disadvantage and without having to provide a reason for this decision. The
opportunity for questions is given at various times. Following this explanation, we
will zoom video or phone call (phone call will only occur if Dr. Tyagi isn't currently
available to zoom call) with our licensed physician co-investigator, Dr. Tyagi, (whose
office is in Montefiore Hospital) at which point the participant will be able to have any
further questions or concerns about the study and the device used addressed by Dr.
Tyagi. Once all questions are satisfactorily addressed, the participant signs the
consent form and we will scan the signed consent form to Dr. Tyagi. Dr. Tyagi will
print, sign and then scan the consent with both signatures back to us. We will print
the signed consent form to file and the participant will be given a copy, as well. Once
both the participant and Dr. Tyagi have signed the consent form and we receive the
scanned copy back from Dr. Tyagi we will begin research procedures. No research
activities will begin until both the subject and the licensed physician Co-I signed the
consent form. This entire process will be documented in the participant's research
chart.
2. * Describe the steps that will be taken to minimize coercion and undue
influence, including assurance that there is sufficient time for subjects to
make an informed decision:
The consent process will include a short summary of the study commitment, an in-
depth explanation and breakdown of each visit, the purpose of the study, the risks
involved and our duty to the research participants, as detailed in the attached
consent form. The voluntary nature of the study will be emphasized.
3. For studies that involve multiple visits, describe the process to ensure
ongoing consent:
At the beginning of each visit the participant will be asked if they have any new
questions or concerns regarding the study and their participation and also be told
about any new information about the study to ensure they are completely informed
and want to continue in the study. Subjects active at the time of approval of MOD
003 will be reconsented.
4. * Steps to be taken to ensure the subjects’ understanding:
A brief explanation of the study will be given on the telephone screening call.
Dr. Tyagi will review and answer any additional questions the subject may have after
the Co-I's/research coordinator's explanation to ensure her understanding. The
participant will be given as much time as needed to think about participating.
5. * Are you requesting an exception to the IRB policy related to the informed
consent process:

  Yes  No

View: Pitt SF: Consent Forms
Consent Forms 
1. Consent Forms:
 
Document
Category
Date Modified
Document History
View Consent Form(0.15)
Consent Form
9/19/2023
History
Refer to the following templates and instructional documents:
Guidance - Consent Wording
Template - Consent Document - Short Form
HRP-090 - SOP - Informed Consent Process for Research  
HRP-091 - SOP - Written Documentation of Consent  
 

View: Pitt SF: Electronic Data Management
Electronic Data Management
1. * Will only anonymous data be collected (select NO if identifiers will be
recorded at anytime during the conduct of the study)?
  Yes  No
Select all identifiers to be collected during any phase of the research including
screening:
Name:

E-mail address:

Social security #:

Phone/Fax #:

Account #:

Medical record #:

Certificate/license #: 
 
 
Internet Protocol (IP) Address:

Web Universal Resource Locators (URLs):

Social security # (for Vincent payment only):

Full face photo images or comparable images: 
Health plan beneficiary #:

Device identifiers/serial numbers:

Vehicle identifiers/serial #/license plate #:

Biometric identifiers, finger and voice prints:

* 
a: Will you be collecting any of the following location data: geographic subdivisions smaller
than a State such as street address, city, county, precinct, zip, geocodes, etc.?
 
  Yes  No
* b: Will you be collecting any date information such as birth date, death, admission,
discharge, date of surgery/service?
  Yes  No
c: List any other unique identifying numbers, characteristics or codes related to an
individual that are to be collected:
d: Will you be collecting any data subject to the General Data Protection Regulation (GDPR)?   Yes  No
* e: Provide a justification for recording Social Security numbers including why it's required,
where it's stored, how it's protected and who will have access:
For vincent
payment
purposes only
* 
For ALL identifiable data collected, will you be
coding the data by removing the identifiers and
assigning a unique study ID/code to protect the
identity of the participant?
  Yes  No
* Will the data be HIPAA de-identified?
  Yes  No
* Briefly describe your plan to store coded data
separately from the identifiable data:
On enrollment, each
participant is assigned a
research code number
that is used to label all
research data collected
on the participant. The
research team secures
the link between the
participants' identity and
the assigned research
code number. The link is
secured in a
password and firewall
protected electronic
database
2. During this study, will restricted data as defined by the University’s Data Risk
Classification matrix ( https://www.technology.pitt.edu/security/data-risk-
classification-and-compliance ) be processed, stored, or transmitted?
  Yes  No 
3. * During this study, will sensitive data (https://www.hrpo.pitt.edu/electronic-data-
security) be collected where disclosure of identifying information could have
adverse consequences for subjects or damage their financial standing,
employability, insurability, educational advancement, reputation or place them
at risk for criminal or civil liability?
  Yes  No

4. * Select all locations where data will be stored or archived(including e.g.,
personal / employer laptop or desktop): If you have access to University owned
or controlled resources, facilities, or repositories, such as computer servers,
please choose that option to comply with the Research Data Management
Interim Policy R1 14.
Please note that to address Research Security Requirements, University data
must be stored in University owned, controlled, or approved repositories,
such as Pitt OneDrive. If UPMC or external electronic repositories must be
used, they must be approved by Pitt IT.
 
Storage Device
DescriptionIdentifiable
Data
Sensitive
Data
De-
Identified/Anonymous
Data
View
UPMC owned
desktop, laptop or
other device
 
no
no
yes
View
UPMC:
Departmental or
Hospital Server 
 
yes
yes
yes
View UPMC: OneDrive
/Sharepoint
 
no
no
yes
5. * Select all technologies being used to collect data or interact with
subjects: Technologies selected in this section may require a Vendor Security
Risk Assessment, which can be requested here.
Web-based site, survey, or other tool
Other
6. * Web Based Technologies – identify all web based technologies to be used to
collect data during any phase of the research:
 
name
Identifiable
View Pitt Redcap Version
 
7. * Other Technologies:
name
Identifiable
Digital Camera
no

View: Pitt SF: Data Safety and Monitoring
Data Safety and Monitoring
1. * Describe your plan to periodically evaluate the data collected regarding both
harms and benefits to determine whether subjects remain safe.  The plan
might include establishing a data monitoring committee and a plan for
reporting data monitoring committee findings to the IRB and the sponsor:
DATA SAFETY AND MONITORING PLAN
The Principal Investigator, Drs. Conklin, and the Co-I Dr. Coffman will ensure that
there are no changes in the risk/benefit ratio throughout the duration of the proposed
studies. Investigators and study personnel will meet weekly to discuss the progress
of the study. Minutes of these meetings will be maintained in the study binder. At
each meeting, the study goals will be discussed and any changes needed to the IRB
application will be made.
Real-time safety monitoring. Our safety monitoring plan involves monitoring of
adverse events at each lab visit during the study. Drs. Conklin and Coffman will be
available at all times by phone/pager during all sessions if adverse events need to
be addressed, as will Sr Research Coordinator Ron Salkeld. In addition, subjects
will be able to call if they experience adverse events while away from the lab, a
procedure we have employed in past studies. The PIs and Co-Is will monitor the
research literature tDCS to identify new findings regarding the overall safety and use
with participants. However, no new risks are anticipated, as the overall risks
associated with transcranial direct current stimulation (tDCS) are considered
minimal or no significant risk.
Data Security. All computers in which data is input and/or maintained have firewalls,
strong password protection, and authorized access to data built in against breaches
of confidentiality. We will emphasize patient confidentiality throughout the study.
Consent forms, and other identifying data will be separated from case-report forms.
Nevertheless, potential breaches will be reviewed with study participants in the
consent form, which will be reviewed in-person and will involve informing potential
participants of the potential for breaches in data security, and of the procedures that
are taken to minimize this possibility. All subject data folders will be maintained in
locked filing cabinets in the PI’s locked laboratory. Access will be given only to the
study investigator and study staff supervised by the investigators. All staff will be
trained on data input and maintenance, as well as confidentiality.
Study review meetings. At monthly meetings, the research team will review the
interests of study participants, assess the safety and utility of study procedures, and
monitor the overall conduct of the study. Quarterly reports will be compiled by the
Research Project Coordinator, under supervision of the PIs, and will be reviewed by
the study team regarding subject accrual (including adherence to protocol regarding
demographics and inclusion/exclusion criteria), adverse events, compliance with
treatment, attrition, breaches of confidentiality, and participant progress.
1. Measurement and Reports of Subjects to Accrual and Adherence to
Inclusion/Exclusion Criteria. These will be reported quarterly as indicated. This will
insure that subjects meet eligibility criteria and that ethnic diversity goals are being
met.
2. Measurement and Reporting of Adverse Events. Any adverse events that are
reported will be examined by both the PI and the study team. Any serious adverse
event will be reported to the IRB and NIH within 24 hours.
3. Measurement and Reporting of Participant Compliance with Treatment Protocol.
Data on compliance to the protocol will be collected and reviewed quarterly by the
team. The review will include an evaluation of attendance records of participants and
compliance records of staff regarding subject recruitment and study procedures. In
addition, the proposed research will be reviewed and approved by the Institutional
Review Board of the University of Pittsburgh. Also, the Principal Investigators will
continually evaluate the progress of the study at weekly meetings with study staff.
The study procedures addressed at these meetings also will include:

a. Subject safety and confidentiality issues
b. Participant recruitment, accrual and retention
c. Data quality and integrity issues. If over the course of the study there is concern
about changes in the risk-benefit ratio, interim analyses will be conducted to
determine if the study should proceed as originally designed.
2.   * Describe your plan for sharing data and/or specimens:
Individuals from the NIH/NIDA will have access to these records as they are the
funding source and we may share de-identified research data in the future with
secondary researchers who also have an interest in this research.
3. If any research data is collected, stored, or shared in a paper format, address
what precautions will be used to maintain the confidentiality of the data:
Data will be kept in locked filing cabinets in a secure suite. On enrollment, each
participant is assigned a research code number that is used to label all
research data collected on the participant. The research team secures the link
between the participants' identity and the assigned research code number.

View: Pitt SF: Risk and Benefits
Risk and Benefits
1. *  Enter all reasonably foreseeable risks, discomforts, hazards, or
inconveniences to the subjects related to subjects’ participation in the
research:
View
Research Activity
Questionnaires 
Common Risks
Some people may find the interview and questionnaires uncomfortable. All
interviews and questionnaires will be completed by trained personnel. The
subject will be given breaks as needed and will be reminded that he/she
doesn't have to answer questions he/she chooses not to and she may stop at
any time. 
Infrequent Risks
No Value Entered 
Other Risks
No Value Entered 
View
Research Activity
tDCS 
Common Risks
No Value Entered 
Infrequent Risks
The risk associated with transcranial electrical stimulation is minimal. There is
a small risk of skin irritation which is minimized by using saline water as the
conductive medium, and through the monitoring of participant discomfort
throughout the procedure. tDCS is seen as a non-invasive medical procedure,
and the commonly reported side-effects in active vs. sham treatments are
itching (39.3% vs 32.9%), tingling (22.2% vs 18.3%), headache (14.8% vs
16.2%), burning sensation (8.7% vs 10%), and discomfort (10.4% vs 13.4%).107
Redness at the electrode site has also been reported. 
Other Risks
No Value Entered 
View
Research Activity
Cue-Reactivity 
Common Risks
Some of the stimuli used have been shown to significantly increase urge to
smoke. The discomfort of increased urge to smoke is anticipated to dissipate
fairly quickly, and over the course of the treatment may lead to less robust
responses. 
Infrequent Risks
No Value Entered 
Other Risks
No Value Entered 
View
Research Activity
Collection and storage of private information 
Common Risks
No Value Entered 
Infrequent Risks
There is a rare possibility of a breach of confidentiality, but we have
safeguards in place to minimize that. All records related to your involvement
in this research study will be stored in a locked file cabinet and all electronic
records are password and firewall protected. Your identity on these records
will be indicated by a case number rather than by your name, although we
may use your initials on certain forms. 
Other Risks
No Value Entered 
2. *  Describe the steps that will be taken to prevent or to minimize risks:
The Neucoconn DC Stimulator Plus used in this study will be routinely tested
(monthly) to ensure that the current and voltage delivered by the device are as
expected based on the settings applied. We will test these parameters using a
standard multimeter (Fluke), and electronic logs of these tests will be maintained by
the PI. Potential risk of skin irritation from transcranial DC stimulation is minimized
by using saline water as the conductive medium, through the monitoring of
participant discomfort throughout the procedure, and by discontinuation of the
procedure if significant discomfort is experienced by the participant. Confidentiality
and loss of Privacy. Information on research participants will be protected for
confidentiality similar to medical records, and will be kept separate from the
research binders in locked metal cabinets and for authorized access only. No

identifiable data will be made available while compiling the study report or when
preparing the eventual results for a journal article. If the cue reactivity or
questionnaires cause the participant discomfort they do not have to answer the
questions and may stop the study at any time.
3. Financial risks - will the subject or insurer be charged for any research
required procedures?
  Yes  No
4. Describe the steps that will be taken to protect subjects’ privacy:
All research procedures will be completed in a private room and with only the
research staff present.
5. What steps will be taken in the event that a clinically significant, unexpected
disease or condition is identified during the conduct of the study:
The PI's would consult with the subject and refer to the appropriate physician for
follow-up.
6. Describe the potential benefit that individual subjects may experience from
taking part in the research or indicate if there is no direct benefit. Do not
include benefits to society or others:
There isn't a direct benefit to the participant for participating in this study; however,
it's possible they may find the study procedures helpful to their urge to smoke.
7. Do you anticipate any circumstances under which subjects might be
withdrawn from the research without their consent?
  Yes  No
*  Describe the circumstances and any procedures for orderly termination:
It is possible that the subject may be removed from the research study by the
researchers if he/she is unable to perform any of the required tasks or does not
show up for scheduled study visits. He/She will always be paid for a session she
attended prior to being formally withdrawn from the study.
8. Describe procedures that will be followed when subjects withdraw from the
research, including partial withdrawal from procedures with continued data
collection and data already collected:
Research data will be kept and reviewed for an indefinite period of time. Research
information collected before excusal or withdrawal from the study will continue to be
used and disclosed by the investigators for the
purposes described above.

View: Pitt SF: Placebo Arm
Placebo Arm
1. *  Is there a commonly used diagnostic/treatment approach that is currently
recognized as being effective for the proposed subjects' disease or condition,
and that will be withheld from subjects assigned to the placebo arm of this
research study:
N/A - the proposed subjects are normal, healthy volunteers
2. Describe the commonly used diagnostic/treatment approaches that will be
withheld from subjects assigned to the placebo arm of this research study:
3. Is enrollment into this study limited to individuals in whom the commonly
used diagnostic/treatment approaches are known to be ineffective or
intolerable?
4. Provide a scientific justification for the placebo-control arm of this research
study:
This is a balanced 2 x 2 design to examine the impact of two new methods to
reduce cue reactivity to personal smoking cues. The placebo arm allows us to
examine the individual and combined impact of the two techniques and compare
them with a time and contact control. The effectiveness of the techniques being
examined, independently or in combination, as methods to reduce cue reactivity to
personal smoking cues has yet to be examined, so a placebo comparison is
warranted.
5. How long will subjects participate in the placebo arm?  Justify why this
duration is necessary:
They will be in the placebo arm for the duration of the study 10 sessions. There are
also follow-up phone calls at 1 week and 1 month post-training. This allows the
placebo arm to serve as a control for subject time and contact.
6. How frequently will the subject's condition or disease be monitored and
compare that to the frequency of monitoring associated with standard care for
this disease/condition?
7. What specific endpoints will result in discontinuing a subject's participation
due to worsening of the subject's disease or condition?
8. What is the risk to subjects who receive no active treatment for their disease
or condition while in the placebo arm?
There is no notable risk, their smoking behavior and craving is expected to remain
stable, whereas we anticipate possible reductions in these measures in the other
arms of the study.
9. Describe the planned involvement of a 'contact person' who interacts with the
subject on a regular basis and who will notify the investigators immediately of
any problems related to the subject's disease or condition:
Note: The involvement of the contact person must also be addressed in the consent
form

View: Pitt SF: Conflict of Interest Ver2
Conflict of Interest
Institutional Financial Interests
1. * To the best of your knowledge, has the University of Pittsburgh optioned or
licensed technology that will be tested or evaluated in this research?
  Yes  No

View: Pitt SF: Ancillary Reviews
Ancillary Reviews 
1. Ancillary reviews or notifications selected below are required based on
previous answers to questions. If a selection is incorrect, return to the
appropriate page and adjust the answers to questions on that page: 
  Conflict of Interest (COI)
  Clinical and Translational Research Center (CTRC)
  Data Security
  Honest Broker
  UPMC Investigational Drug Service
  Pitt Medical School Review
 Pitt+Me  
  IND & IDE Support(IIS)
  Radioactive Drug Research Committee (RDRC)(study involves the evaluation
or use of procedures that emit ionizing radiation)
  ORP Business Manager (required for industry sponsored studies)
  Religious Directives
  Scientific Review
  Health Record Research Request (R3) (required if using UPMC clinical data
and authorization for other UPMC data sources for research)
  UPMC Office of Sponsored Programs and Research Support (using UPMC
facilities and/or UPMC patients during the conduct of the study)
2. Additional ancillary reviews the PI may choose to include as needed for the
research:
  Human Stem Cell Oversight (hSCRO)
  Institutional Biosafety Committee (IBC)(study involves deliberate transfer of
recombinant or synthetic nucleic acid molecules)

View: Pitt SF: Clinical Trials
Good Clinical Practice (GCP) Training
1. * Regardless of funding source, is this study a clinical trial (as defined by the
NIH)?
  Yes  No
ClinicalTrials.gov Information
Visit the University of Pittsburgh Office for ClinicalTrials.gov website or contact ctgov@pitt.edu
for further information.  
2. * Was this study registered, or will it be registered, on ClinicalTrials.gov?
  Yes  No
3. * Is the University of Pittsburgh or UPMC the Sponsor Organization for this
study record?
  Yes  No 
* Who will be the Responsible Party for this study record?
Principal Investigator of this IRB application

View: Pitt SF: Supporting Documents
Supporting Documents
1. Attach any additional supporting documents not previously uploaded. Name
the documents as you want them to appear in the approval letter:
 Document
Category
Date Modified
Document History
There are no items to display

View: Pitt Create
Add Storage Information
1. * Select a Storage Type:
UPMC owned desktop, laptop or other device
2. Description:
3. * Will identifiable data be stored in this location?
  Yes  No
4. * Will sensitive data be stored in this location?
  Yes  No
5. Will de-Identified or anonymous data be stored in this location?
  Yes  No
6. * Is anti-virus software installed and up to date on all devices and are the
operating systems kept up-to-date on all devices?
  Yes  No
7. Provide additional information as needed:

View: Pitt Create
Add Storage Information
1. * Select a Storage Type:
UPMC: Departmental or Hospital Server 
2. Description:
3. * Will identifiable data be stored in this location?
  Yes  No
4. * Will sensitive data be stored in this location?
  Yes  No
5. Will de-Identified or anonymous data be stored in this location?
  Yes  No
6. Provide additional information as needed:

View: Pitt Create
Add Storage Information
1. * Select a Storage Type:
UPMC: OneDrive /Sharepoint
2. Description:
3. * Will identifiable data be stored in this location?
  Yes  No
4. * Will sensitive data be stored in this location?
  Yes  No
5. Will de-Identified or anonymous data be stored in this location?
  Yes  No
6. Provide additional information as needed:
7. Will access to the files or folders be restricted to only those research team
members involved in the study(e.g., Specific people are granted access)?
  Yes  No 

View: Pitt Risk
Risk
1. * Research Activity:
Questionnaires
2. Common Risks:
Some people may find the interview and questionnaires uncomfortable. All
interviews and questionnaires will be completed by trained personnel. The subject
will be given breaks as needed and will be reminded that he/she doesn't have to
answer questions he/she chooses not to and she may stop at any time.
3. Infrequent Risks:
4. Other Risks:

View: Pitt Risk
Risk
1. * Research Activity:
tDCS
2. Common Risks:
3. Infrequent Risks:
The risk associated with transcranial electrical stimulation is minimal. There is a
small risk of skin irritation which is minimized by using saline water as the
conductive medium, and through the monitoring of participant discomfort throughout
the procedure. tDCS is seen as a non-invasive medical procedure, and the
commonly reported side-effects in active vs. sham treatments are itching (39.3% vs
32.9%), tingling (22.2% vs 18.3%), headache (14.8% vs 16.2%), burning sensation
(8.7% vs 10%), and discomfort (10.4% vs 13.4%).107 Redness at the electrode site
has also been reported.
4. Other Risks:

View: Pitt Risk
Risk
1. * Research Activity:
Cue-Reactivity
2. Common Risks:
Some of the stimuli used have been shown to significantly increase urge to smoke.
The discomfort of increased urge to smoke is anticipated to dissipate fairly quickly,
and over the course of the treatment may lead to less robust responses.
3. Infrequent Risks:
4. Other Risks:

View: Pitt Risk
Risk
1. * Research Activity:
Collection and storage of private information
2. Common Risks:
3. Infrequent Risks:
There is a rare possibility of a breach of confidentiality, but we have safeguards in
place to minimize that. All records related to your involvement in this research study
will be stored in a locked file cabinet and all electronic records are password and
firewall protected. Your identity on these records will be indicated by a case number
rather than by your name, although we may use your initials on certain forms.
4. Other Risks: