Effect of a Non-Invasive Brain Stimulation Technique on Smoking Cessation Behaviors
Phase: NA
Conditions: Tobacco Use Disorder
Sponsor: University of Minnesota

Effect of a Non-Invasive Brain Stimulation Technique on Smoking Cessation Behaviors 
 
NCT03386253 
 
05/16/2018 

Effect of a Non-Invasive Brain Stimulation Technique on Smoking Cessation Behaviors 
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PROTOCOL TITLE: 
Effect of a Non-Invasive Brain Stimulation Technique on Smoking Cessation Behaviors 
 
PRINCIPAL INVESTIGATOR: 
Michael Kotlyar, PharmD 
Associate Professor 
Department of Experimental and Clinical Pharmacology 
612-625-1160 
kotly001@umn.edu 
 
Co-Investigators 
Y. Jazmin Camchong, PhD 
Assistant Professor 
Psychiatry 
612-624-0134 
camch002@umn.edu 
 
Dorothy Hatsukami, PhD 
Professor 
Department of Psychiatry 
612-626-2121 
hatsu001@umn.edu 
 
Kelvin Lim, MD 
Professor 
Department of Psychiatry 
612-626-6772 
kolim@umn.edu 
 
 
 
VERSION NUMBER/DATE: 
Version 3.0 
Version Date: 05-16-18 

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REVISION HISTORY 
 
Revision # 
Version Date 
Summary of Changes 
Consent Change? 
       #1 
     11/28/17 
Added weight measurement at Follow-Up 
visits 
               YES 
      # 2 
     5/16/18 
Adding functional magnetic resonance 
imaging (fMRI) 
               YES 

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Table of Contents 
After completing your protocol, right click on the Table of Contents below and select 
“Update Field.” If prompted, select “Update entire table.” This will automatically 
update the protocol sections and page numbers for you. Do this also each time you 
modify your protocol after initial approval. 
1.0 
Objectives .................................................................................................................................... 6 
2.0 
Background .................................................................................................................................. 6 
3.0 
Study Endpoints/Events/Outcomes .............................................................................................. 7 
4.0 
Study Intervention(s)/Investigational Agent(s) ............................................................................ 7 
5.0 
Procedures Involved ..................................................................................................................... 8 
6.0 
Data and Specimen Banking ...................................................................................................... 10 
7.0 
Sharing of Results with Participants .......................................................................................... 10 
8.0 
Study Duration ........................................................................................................................... 11 
9.0 
Study Population ........................................................................................................................ 11 
10.0 
Vulnerable Populations .............................................................................................................. 12 
11.0 
Local Number of Participants .................................................................................................... 12 
12.0 
Local Recruitment Methods ....................................................................................................... 12 
13.0 
Withdrawal of Participants ........................................................................................................ 13 
14.0 
Risks to Participants ................................................................................................................... 13 
15.0 
Potential Benefits to Participants ............................................................................................... 14 
16.0 
Data Management ...................................................................................................................... 14 
17.0 
Confidentiality ........................................................................................................................... 14 
18.0 Provisions to Monitor the Data to Ensure the Safety of Participants ........................................ 15 
19.0 
Provisions to Protect the Privacy Interests of Participants ........................................................ 15 
20.0 
Compensation for Research-Related Injury ............................................................................... 15 
21.0 
Consent Process ......................................................................................................................... 15 
22.0 
Setting ........................................................................................................................................ 16 
23.0 Multi-Site Research: N/A .......................................................................................................... 16 
24.0 Resources Available ................................................................................................................... 16 
25.0 References .................................................................................................................................. 16 
 

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ABBREVIATIONS/DEFINITIONS 
• 
tDCS – transcranial direct current stimulation 
• 
fMRI – functional magnetic resonance imaging 
• 
FC – functional connectivity 
• 
NAcc – nucleus accumbens 
• 
DLPFC - dorsolateral prefrontal cortex 
• 
MNWS – Minnesota Nicotine Withdrawal Scale 
• 
QSU – Questionnaire of Smoking Urges 
• 
CO – carbon monoxide 

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STUDY SUMMARY 
 
Study Title 
Effect of a Non-Invasive Brain Stimulation 
Technique on Smoking Cessation Behaviors 
Study Design 
Randomized Double-Blind Pilot Study 
Primary Objective 
To determine the feasibility of using tDCS (a non- 
invasive brain stimulation technique) as a treatment 
for smoking cessation 
Research 
Intervention(s)/Investigational 
Agents 
Transcranial direct current stimulation (tDCS) 
IND/IDE # (if applicable) 
n/a 
Investigational Drug Services 
# (if applicable) 
n/a 
Study Population 
medically stable smokers 
Sample Size (number of 
participants) 
20 to complete the study 
Study Duration for Individual 
Participants 
Approximately 6 weeks 

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1.0 
Objectives 
1.1 Aim 1: To determine the feasibility of using transcranial Direct Current 
Stimulation (tDCS) in a population of smokers interested in cessation 
 
2.0 
Background 
2.1 
Significance of Research Question/Purpose: The morbidity and mortality 
associated with smoking is well characterized, with the most recent Surgeon 
General’s report estimating that approximately 480,000 deaths annually in the 
United States are attributable to smoking.1 Although 70% of smokers indicate a 
desire to quit, the best current treatments result in less than 30% achieving long- 
term abstinence. New treatments for tobacco dependence are introduced rarely 
with only three medications currently approved for increasing smoking cessation 
rates (i.e. medicinal nicotine, varenicline, bupropion). Clearly, additional 
therapies are needed 
2.2 
Preliminary / Existing Data: Transcranial direct current stimulation 
(tDCS) is a non-invasive brain stimulation technique in which a weak electrical 
current (2mA or less) is applied to the scalp via anodal and cathodal electrode 
sponges, causing either increases or decreases in cortical excitability, respectively. 
Use of this technology has been studied for the treatment of several disorders (e.g. 
depression, Alzheimer’s disease, Parkinson’s disease) and has been suggested as a 
potential treatment modality for addiction. Drs. Camchong and Lim have 
identified, using functional magnetic resonance imaging (fMRI), brain biomarkers 
that support long-term abstinence from alcohol in those with alcohol use disorder. 
Specifically, cross-sectional and longitudinal findings suggest that higher 
functional connectivity (FC) between the nucleus accumbens (NAcc) and 
dorsolateral prefrontal cortex (DLPFC) is a potential brain biomarker that is 
associated with abstinence. Long-term abstinent alcoholics (7 years of abstinence) 
have higher resting FC between NAcc and DLPFC when compared to non- 
substance abusing healthy controls. Short-term abstinent alcoholics (11 weeks of 
abstinence) have intermediate FC (lower than long-term abstinent alcoholics and 
higher than controls).2, 3 Further, lower FC between NAcc and DLPFC at 11 
weeks of abstinence can be a predictor of subsequent relapse (with 74% 
accuracy).4 Moreover, in a pilot longitudinal study examining resting FC of NAcc 
at 5 and 13 weeks of abstinence in individuals with substance use disorder, FC 
between NAcc and DLPFC decreased from 5 to 13 weeks of abstinence in 
subsequent relapsers, while it increased in subsequent abstainers.5 One 
interpretation of this data is that long-term abstinence is supported by a 
compensatory mechanism that mediates proper executive function over reward 
(which is mediated by DLPFC-NAcc FC). This information provides a potential 
brain marker that could be an intervention target if methods can be identified that 
increase FC between DLPFC and NAcc. 
Cognitive flexibility, the ability to change maladaptive behavior, depends on 
DLPFC input to NAcc. 6 DLPFC transmits reward representations to NAcc 
through glutamatergic projections that guide goal-directed behavior. 7 If DLPFC 

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fails to activate when required, as often observed in substance use disorder, target 
neurons in the NAcc core do not receive critical information needed to select the 
appropriate outcome, causing acquired maladaptive response patterns to persist 
(e.g. drug consumption).6 Higher FC between DLPFC and NAcc may be 
achieved by stimulating DLPFC while subjects perform tasks that require 
cognitive flexibility, an aspect of executive functioning. 
Transcranial direct current stimulation (tDCS) has shown in both healthy subjects 
and in patients (e.g. Parkinson’s disease, stroke, and depression) to modulate 
synaptic strengthening and neurotransmitter-dependent plasticity underlying 
changes in behavior and learning.8 It therefore has the potential to increase 
functional connectivity between NAcc and DLPFC when paired with a cognitive 
task engaging this pathway. As previously described, strengthening this pathway 
should facilitate proper selection of goal-directed behavior and decrease craving 
in those with substance use disorder.9 
There is currently limited data regarding the efficacy of tDCS on smoking 
cessation and no data regarding the efficacy of combining tDCS with a concurrent 
task requiring cognitive flexibility. Although studies have assessed the effect of 
tDCS on smoking behavior, these have not combined stimulation with a task 
requiring cognitive flexibility nor have these studies assessed cessation outcomes. 
Instead, smoking cues were presented either immediately prior to, during or 
immediately after neurostimulation10-14 with the outcomes assessed being either 
cue induced craving severity, number of cigarettes smoked during the days of 
stimulation or using laboratory based smoking choice paradigms. These studies 
have generally found small but positive effects in these measures. However by 
not combining tDCS with the cognitive flexibility task, these studies may not 
have been able to maximize the effects of this intervention. 
 
3.0 
Study Endpoints/Events/Outcomes 
3.1 
Primary Endpoint/Event/Outcome: As a pilot study, the main objective of 
this investigation is to determine the feasibility of using the proposed approach as 
a method by which to increase smoking cessation rates. The primary endpoint is 
therefore to determine if recruiting smokers into a study evaluating tDCS will be 
feasible and if the intervention is well tolerated by smokers. 
3.2 
Secondary Endpoint(s)/Event(s)/Outcome(s): Secondary endpoints include 
measures associated with smoking cessation outcomes including time to smoking 
lapse, time to smoking relapse, number of cigarette smoked, severity of craving 
and severity of withdrawal symptom score. We will also assess impulsivity as 
tDCS may impact this measure.  fMRI measures will be assessed in the sub-
population of subjects enrolled after protocol revision # 3 is approved and after 
all preparations to enroll subjects into this portion of the study are complete.  
4.0 
Study Intervention(s)/Investigational Agent(s) 
4.1 
Description: The tDCS will be performed with the Neuroelectrics Starstim 
NE (Neuroelectrics Barcelona, Spain). This device is located in the MnDRIVE 
Non-invasive Neuromodulation Laboratory (Room 247 at the Delaware Clinical 

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Research Unit of the CTSI). 
 
4.2 
Drug/Device Handling: To minimize risks of tDCS, study staff will be 
trained in and use standards of administration that have been shown as safe in 
numerous other studies using transcranial direct current stimulation. A recent 
review of the safety of tDCS found no reports of serious adverse effects or 
irreversible injury across over 33,200 session and 1,000 subjects with repeated 
sessions.15 The length of administration of the current, size of electrode sponges 
used, and method of applying stimulation are no higher than those that have been 
demonstrated as safe. 
4.3 
IND/IDE. In studies using tDCS, approval of the device in research has 
generally been granted without an investigational device exemption due to 
meeting criteria for non-significant risk (NSR). A recent review of regulatory 
considerations for the clinical and research use of tDCS concluded that in the 
United States, “IRB’s ubiquitously (at a minimum overwhelmingly) designate 
tDCS trials NSR (see adverse event discussion above), thus not requiring a formal 
IDE application to the FDA.” 16 
4.4 
Biosafety: N/A 
 
5.0 
Procedures Involved 
5.1 Study Design: This study is a randomized double-blind pilot study in which 
subjects will receive either active or sham tDCS 
5.2 Study Procedures: The following procedures will occur during the study 
5.2.1 Screening visit: Initial eligibility will be assessed via a phone interview. 
Those likely to qualify will be scheduled for a screening visit at which written 
informed consent will be obtained and eligibility confirmed. Medical, psychiatric 
and smoking history will be obtained via subject report with smoking status 
biochemically confirmed (via an exhaled carbon monoxide (CO) concentration of 
> 8 ppm or a urinary nicotine test strip = 6). Baseline levels of a variety of 
measures such as severity of smoking urges, severity of withdrawal symptoms, 
extent of nicotine dependence and how subjects evaluate their current cigarettes 
will be assessed via questionnaires. Height and weight will be measured. Those 
who qualify will be scheduled for a week during which they will come in daily for 
5 consecutive days to receive tDCS treatments (active or sham) and will be asked 
to maintain a daily tobacco use diary in order to assess baseline levels of smoking. 
Subjects enrolled after revision # 3 has been approved and all preparations to 
enroll subjects into the scanning portion of the study are complete will be asked to 
come in for two additional visits to collect fMRI data: one visit before tDCS 
treatments begin, and a second visit after all tDCS treatments are completed. 
5.2.2 MRI scanning visits (2 visits, 1 visit occurring during the week prior to 
and the other visit occurring during the week following the tDCS visits):  
Participants will undergo an MRI scan (3T), which takes about 75 to 80 minutes.  
MRI involves taking pictures of the participant's brain, from which the properties 
of certain brain tissues can be measured.  These scans are strictly for research 

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purposes and therefore will not receive a clinical or medical interpretation. For 
the scan, the participant will be asked to lie down quietly on a bed, and the bed 
will slide into the scanner. Once the participant is inside the scanner, the imaging 
will begin. During the scan, the participant will be asked to lie quietly in the 
scanner with their eyes closed and may also be asked to perform a cognitive task 
(e.g., reversal learning task). The MRI scan will be performed at the University of 
Minnesota’s Center for Magnet Resonance Research.  
5.2.3 tDCS Visits (5 visits on consecutive days): At each of these visits, subjects  
will receive active or sham tDCS. The length of stimulation and the current used 
is consistent with the parameters previously found in clinical studies of alcohol 
dependence to reduce relapse.17 Specifically, subjects will receive two 13 minute 
2-mA sessions to the left DLPFC at each visit with a rest interval (no stimulation) 
of 20 minutes in between. 17, 18 While receiving stimulation, subjects will perform 
cognitive training tasks drawn from the commercially-available Brain HQ suite 
of tasks.  Over each 46 minute period (i.e., the two 13 minute tDCS session 
separated by 20 minutes in between), each of 7 tasks will be performed for 
approximately 6 minutes. These tasks are designed to be adaptive based on 
participants’ performance and therefore are more engaging than non-adaptive 
tasks. Multiple peer-reviewed medical and science journal articles have been 
published on Brain HQ exercises and assessments in varied clinical populations. 
Its commercial availability also makes Brain HQ amenable to potential future 
large scale deployment. Table 1 summarizes the Brain HQ tasks that will be 
utilized 
 
Table 1: Brain HQ Executive Function Tasks 
Task 
Modality 
Domain 
Description 
Freeze Frame 
Visual 
Behavioral Inhibition 
Must decide if pictures match one presented at start 
of task. Respond ONLY when pictures DO NOT 
match. 
Mixed Signals 
Visual & 
Auditory 
Behavioral inhibition 
Listen to a number, letter of color while looking at a 
set of numbers letters or colors. Decide if the two 
stimuli match quickly as possible. 
Divided Attention 
Visual 
Behavioral inhibition; 
Set shifting 
Decide if two objects match depending on rule 
(color vs. shape). 
Mind Bender 
Visual 
Set shifting 
Must respond based on two competing rules 
depending on the type of stimuli 
Card Shark 
Visual 
Working Memory 
Visual n-Back 
Auditory Ace 
Auditory 
Working Memory 
Auditory n-back task 
Juggle Factor 
Visual 
Working Memory 
Presented with a sequence of numbers that are 
placed within moving circles; Must reconstruct the 
sequence in the right order & locations. 
At the beginning of each tDCS visit, participants will be assessed for number of 
cigarettes smoked 24 hours prior to the session, the time since last cigarette and 
exhaled CO levels. A cigarette evaluation scale will be completed at each visit. 
Additionally, adverse events, smoking urges and nicotine withdrawal symptom 
severity will be assessed before and after each session using several 
questionnaires. At the first tDCS session, urine will be collected to be analyzed at 
a later time for markers of cigarette smoking (e.g., cotinine concentrations). Prior 
to the first and after the last tDCS session, participants will also complete an 
impulsiveness questionnaire as this parameter is thought to be affected by tDCS, a 

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questionnaire assessing nicotine dependence as well as a questionnaire assessing 
motivation and self-efficacy to quit smoking.19 Total participation time at each 
visit is not expected to exceed 2 hours per day. 
At these visits, participants will be provided a smoking cessation treatment 
manual (Clearing the Air) and begin preparation for the quit date, which will be at 
the end of the 5th visit. The standardized content of the brief (10 min) behavioral 
treatment session provided to participants will include discussing benefits of 
quitting, ways to prepare the environment to minimize smoking cues (e.g., 
removing ashtrays), and methods to reduce craving and withdrawal symptoms 
(e.g., deep breathing). Participants will also keep track of situations associated 
with smoking and begin to develop a plan to deal with these situations. 
This tDCS device to be used in this study is located in the MnDRIVE Non- 
invasive Neuromodulation Laboratory. There is currently no evidence of serious 
side-effects.15 Mild side-effects that typically resolve upon discontinuing tDC 
include light itching under the electrode at the beginning of administration, 
headache, fatigue, and nausea. The subject may choose to discontinue stimulation 
at any time during the session if experiencing excessive discomfort or side effects. 
Although seizures are not a known risk of tDCS intervention,20 anyone with a 
history or a risk for seizures will be excluded from the study. No other risks 
related to tDCS are anticipated. 
5.2.4 Post Cessation Visits (4 visits): Follow-up visits will occur at each of 4 
weekly visits. At each visit, smoking diaries will be collected and exhaled CO 
will be measured. Urine will be collected at the week 1, 2 and 4 visits. Weight 
will be measured at week 1, 2, 3 and 4 visits. Questionnaire assessing craving and 
withdrawal symptoms severity will be assessed as will the effects that 
participants report from smoking (via the cigarette evaluation scale21). 
 
5.3 
Individually Identifiable Health Information: All information is collected 
directly from subjects (i.e., medical records will not be requested) and this is not a 
treatment study. The data being collected therefore does not meet the definition 
of PHI. 
 
5.4 Use of radiation: N/A 
5.5 Use of Center for Magnetic Resonance Research: This study has been reviewed by the 
CMRR (Project Application Review System application # 5101) 
 
6.0 
Data and Specimen Banking 
6.1 Storage and Access: Urine will be collected from subjects at the Day 1 and Weeks 1,2 
and 4 visits. The samples will be stored in freezers located in labs used by faculty in the 
ECP department (currently these freezers are located on the 5th floor of 717 Delaware 
Ave). Samples will be stored until later batch analysis can be completed.  
7.0 
Sharing of Results with Participants 
7.1 Study results will not be shared with participants. 

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8.0 
Study Duration 
• 
The anticipated duration for an individual participant’s participation in the 
study is approximately 6 weeks (depending in part on length of time 
between the screening visit and first tDCS visit). 
• 
Data collection is expected to be complete within 1 year of starting the 
study. 
 
9.0 
Study Population 
9.1 Inclusion Criteria: To be eligible subjects must: 
a) Be between the ages of 18 and 64 
b) Smoke (on average) at least 5 cigarette per day 
c) Be motivated to quit smoking 
9.2 Exclusion Criteria: Subjects will be excluded if they: 
a) Regularly use tobacco products other than cigarettes (> 9 times per 
month) 
b) Have any major medical or psychiatric condition that is unstable and 
renders them unable to participate in the study. 
c) Have any medical condition with neurological sequelae (e.g., stroke, 
seizures). 
d) History of loss of consciousness of greater than 30 minutes duration or 
loss of consciousness with neurological sequelae 
e) Have any medical condition or use any medication that would either 
increase risk of subjects participating in this study (e.g., medications that 
lower the seizure threshold) or that would impact measures of interest 
(e.g. smoking cessation medications). 
f) Have any contraindications for MRI scanning (e.g., metal implants, 
pacemakers or any other implanted electrical device, injury with metal, 
braces, non-removable body piercings, pregnancy) 
g) Are pregnant or planning to become pregnant during the study 
h) Have any contraindications to tDCS (e.g., current use of 
pacemaker, intracranial electrodes or implanted defibrillator). 
9.3 Screening: At the screening visit, subjects will complete a serious of 
questionnaires including those that ask about medical history, smoking 
history and motivation to quit smoking. All inclusion / exclusion will be 
based on self-report except for smoking status which will be confirmed via 
an exhaled carbon monoxide (CO) concentration of > 8 ppm or a urinary 
nicotine test strip reading of 6. Non-pregnant status will be confirmed via a 
urine pregnancy test. 
 

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10.0 Vulnerable Populations 
10.1 Vulnerable Populations: 
☐ Children 
☐ Pregnant women/Fetuses/Neonates 
☐ Prisoners 
☐ Adults lacking capacity to consent and/or adults with diminished 
capacity to consent, including, but not limited to, those with acute 
medical conditions, psychiatric disorders, neurologic disorders, 
developmental disorders, and behavioral disorders 
☐ Approached for participation in research during a stressful situation such 
as emergency room setting, childbirth (labor), etc. 
☐ Disadvantaged in the distribution of social goods and services such as 
income, housing, or healthcare 
☐ Serious health condition for which there are no satisfactory standard 
treatments 
☐ Fear of negative consequences for not participating in the research (e.g. 
institutionalization, deportation, disclosure of stigmatizing behavior) 
☐ Any other circumstance/dynamic that could increase vulnerability to 
coercion or exploitation that might influence consent to research or 
decision to continue in research 
☐ Undervalued or disenfranchised social group 
☐ Members of the military 
☐ Non-English speakers 
☐ Those unable to read (illiterate) 
☐ Employees of the researcher 
☐ Students of the researcher 
☒ None of the above 
 
11.0 Local Number of Participants 
11.1 Local Number of Participants to be Consented: We plan on recruiting 
subjects until approximately 20 have completed the study.  We expect that 
as many as 50 subjects will undergo the consent process. Some of those that 
attend the screening visit will likely not meet inclusion / exclusion criteria 
whereas others will not be interested in participating. 
 
12.0 Local Recruitment Methods 
12.1 Recruitment Process: Advertisements for the study will be placed in various 
print and on-line sources and via flyers. Interested participants will call the 
phone number listed. Study staff will explain the study to potential study 
subjects. Individuals that indicate an interest in participating in the study 
will then be screened by telephone to see if they are likely to qualify for the 
study. Additionally subjects that in previous studies agreed to be contacted 
regarding other research opportunities may be called – in this case, subjects 

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will be informed why they are being called with the telephone screening 
process being the same as for subjects who contacted us after seeing the 
study advertised. 
12.2 Recruitment Materials: Flyers and advertisements placed in local 
publications or on on-line resources (for example, Craigslist) will be used to 
recruit participants. 
12.3 Payment: Subjects will receive $20 for each visit that they complete (e.g. 
screening visit, MRI scans, 5 visits at which tDCS will be administered, 4 
follow-up visits). Subjects who attend all study visits and comply with all 
study related procedures will receive a $60 bonus. Subjects can therefore 
receive up to $300 for completing the entire study. Payment will be provided at 
the end of each visit in the form of a pre-paid debit card. 
 
13.0 Withdrawal of Participants 
13.1 Withdrawal Circumstances: Participants will be withdrawn from the study if 
they report any side effects of greater than moderate severity or that raise 
any safety concerns. Subjects may also be withdrawn from the study if they 
fail to follow study procedures (e.g., show up to scheduled study visits). 
Additionally, subjects will be told that participation is voluntary and that 
they may discontinue participation at any time for any reasons. 
13.2 Withdrawal Procedures: Subjects who withdraw from the study after having 
received tDCS will be asked if they can be contacted by telephone to 
ascertain smoking status. We will attempt to contact subjects by telephone 
who do not show up to scheduled visit to ascertain if they wish to continue 
to participate in the study (and if not, why not) and to determine smoking 
status. 
 
14.0 Risks to Participants 
14.1 
Foreseeable Risks: The device to be used in this study is a transcranial 
direct current stimulator - tDCS. tDCS is considered to be a safe brain stimulation 
technique that rarely results in adverse events. There is currently no evidence of 
serious side-effects. Mild side-effects that typically resolve upon discontinuing 
tDCS include light itching under the electrode at the beginning of administration, 
headache, fatigue, and nausea. The subject may choose to discontinue stimulation 
at any time during the session if experiencing excessive discomfort or side effects. 
Although seizures are not a known risk of tDCS intervention,20 anyone with a 
history or a risk for seizures will be excluded from the study. No other risks 
related to tDCS are anticipated. 
MRI risks: Individuals will complete a screening questionnaire for 
contraindications of MRI scanning which will be reviewed by CMRR staff at the 
University of Minnesota. A determination will be made regarding the level of risk 
to the subject and whether they are approved for scanning.     
There are no known risks to humans due to the static magnetic field. Subjects, 
operators, and guests are screened prior to entering the magnetic environment, 

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and frequently reminded of the potential danger of introducing magnetic objects 
to the controlled area. Subjects are excluded from the study if they have any 
implanted devices. Subjects are always accompanied when near the magnet, and 
reminded to move slowly and carefully as they enter and leave the magnet. 
The risk of tissue damage by energy emitted by the MRI device is controlled by 
compliance with FDA guidelines for commercial MRI devices. Safety devices are 
in place so that the magnet will cease to operate should any parameters begin to 
exceed their preset safety limits. The risk of peripheral nerve stimulation by dB/dt 
is limited by safety devices. The noise levels generated by each scan are 
monitored to ensure adherence to guidelines. In addition, subjects are provided 
with earplugs and secondary protection (foam covering or headphones) to 
increase comfort during the scan..   
14.2 
Reproduction Risks: There is limited data regarding the risks of tDCS to 
an embryo or fetus although since tDCS is a localized brain stimulation treatment, 
it is unlikely to have reproductive risks.22  The risks of MRI to fetuses are 
unknown.  We will therefore exclude women who are pregnant or are planning to 
become pregnant during the study. 
14.3 Risks to Others: There are no anticipated risks to others. 
 
15.0 Potential Benefits to Participants 
15.1 Potential Benefits: As this is not a treatment study, there is no direct benefit 
to individual participants. 
 
16.0 Data Management 
Data Analysis Plan: Data collected in this pilot study will be used as preliminary 
data and proof of concept to facilitate the design of and estimate power for 
subsequent larger grants. Descriptive statistics will conducted and effect sizes will 
be estimated. Linear mixed models will be used to examine time, group (sham vs. 
active) and group by time effects for various continuous outcome measures (e.g. 
craving). Survival analyses will be used to examine group differences on time to 
relapse to smoking. 
16.1 Power Analysis: As this is a pilot study, no power analysis was done. 
16.2 Data Integrity: In order to ensure that data entry is correct, data collected on 
paper questionnaires will be entered twice with the two entries compared 
and any discrepancies resolved. 
 
17.0 Confidentiality 
17.1 
Data Security: To ensure confidentiality, all subjects will be assigned a 
study identification code to be used on all data collection forms except those for 
which use of personal identifiers is mandatory (e.g., informed consent form). 
Forms that link the name of the participant and the subject identification code will 
be kept in a locked cabinet or office or in an electronic file stored on password 

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protected secure computer servers maintained by the University. Visits will be 
conducted at the CTSI, therefore there will be a record of the subject’s 
participation in the CTSI records although a copy of the consent form will not be 
placed in the participants’ medical records. 
 
18.0 Provisions to Monitor the Data to Ensure the Safety of 
Participants 
The CTSI monitoring group will be asked to monitor this study using their 
standard procedures. 
 
19.0 Provisions to Protect the Privacy Interests of Participants 
19.1 
Protecting Privacy: During the consent process, subjects will be told that 
they can discontinue participation at any time for any reason. Furthermore, they 
are free to not answer any questions asked on the questionnaires. However since 
certain information is needed to assess eligibility or to assess measures of interest, 
declining to answer certain questions may lead to a subject not being eligible to 
participate or to continue with the study. 
 
20.0 Compensation for Research-Related Injury 
20.1 Compensation for Research-Related Injury: No compensation is available in 
the event of research related injury. 
 
21.0 Consent Process 
21.1 
Consent Process (when consent will be obtained): Informed consent will 
be obtained at the screening visit. Subjects will have the opportunity to read the 
consent document and ask any questions that they have. A member of the study 
staff will then ask the subject questions to make sure that they understand the 
study procedures. No study procedures will be administered until the subject has 
signed the consent form. 
21.2 Waiver or Alteration of Consent Process (when consent will not be 
obtained): N/A 
 
21.3 Non-English Speaking Participants: N/A 
 
21.4 
Participants Who Are Not Yet Adults (infants, children, teenagers under 
18 years of age): Individuals under the age of 18 will be excluded from the study. 
Subjects will be asked to present ID at the screening visit to confirm that they are 
over the age of 18. 
 
21.5 
Cognitively Impaired Adults or adults with fluctuating or diminished 
capacity to consent: We are not planning on enrolling subjects with fluctuating or 
diminished capacity to consent.  Subjects that appear during the consent process 

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to have impaired capacity to consent will be excluded from the study. 
21.6 Adults Unable to Consent: N/A 
 
22.0 Setting 
22.1 
Research Sites: Potential subjects will be recruited via the use of flyers 
and advertisements placed in local publications or on on-line resources (for 
example, Craigslist). Additionally subjects that in previous studies agreed to be 
contacted regarding other research opportunities may be called. Study visits will 
occur in the Delaware Clinical Research Unit (formerly part of the Clinical and 
Translational Research Institutes (CTSI) facilities).  Scans will be conducted at 
the Center for Magnetic Resonance Research (CMRR). 
 
23.0 Multi-Site Research: N/A 
 
24.0 Resources Available 
This study is being supported by a grant from the Academic Health Center Seed 
Grant Program. The tDCS device being utilized in this study is located in the 
MnDRIVE Non-invasive Neuromodulation Laboratory (Room 247 at the 
Delaware Clinical Research Unit of the CTSI). The personnel assisting with this 
study (e.g., study coordinators) work with the research groups of the investigators. 
Based on previous studies, we believe that that there are adequate smokers in the 
community interested in participating in research studies in order to meet 
recruitment goals. However, as a feasibility study, the ability to recruit smokers is 
one of the outcomes of interest. 
 
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