Role of Transcranial Direct Current Stimulation to Decrease Impulsivity and Compulsivity in Individuals With Obesity
Phase: NA
Conditions: Impulsivity, Compulsive Overeating, Obesity
Sponsor: Minneapolis Veterans Affairs Medical Center

Study Document
Study Title: Role of Transcranial Direct Current Stimulation to Decrease Impulsivity and
Compulsivity in Individuals with Obesity
Short Title: tDCS for Impulsivity and Compulsivity in Obesity
NCT: NCT04405089
Document Type: Protocol (includes statistical analysis plan)
Document Date: 24JUL2018

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PROTOCOL TITLE: 
Role of Transcranial Direct Current Stimulation to Decrease Impulsivity and Compulsivity 
in Individuals with Obesity 
PRINCIPAL INVESTIGATOR or FACULTY ADVISOR: 
Shalamar Sibley, MD, MPH 
Metabolic Section, Department of Medicine 
sible004@umn.edu 
 
CO-INVESTIGATORS: 
Charles Billington, MD 
Metabolic Section, Department of Medicine 
billi005@umn.edu 
 
Kelvin Lim, MD 
Department of Psychiatry 
kolim@umn.edu 
 
VERSION NUMBER/DATE: 
July,24,2018  
 

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1.  STUDY SUMMARY 
 
Study Title 
Role of Transcranial Direct Current Stimulation to 
Decrease Impulsivity and Compulsivity in Individuals 
with Obesity 
 
Study Design 
Double-blind, randomized, sham-controlled pilot clinical 
study 
Primary Objective 
Primary Objective: To determine if there is a 
treatment-related decrease in measures of impulsivity 
and compulsivity with tDCS compared to sham 
Hypothesis: tDCS treatment decreases impulsivity and 
compulsivity. 
 
Secondary Objective(s) 
Secondary Objectives: (1)To compare tDCS 
treatment-related change in weight loss compared to 
sham (randomized intervention) in individuals prior to 
undergoing their 16 week structured behavior 
modification weight loss program (usual care) in the 
Minneapolis VAMC’s Move Mass Program 
 
Hypothesis: tDCS treatment leads to weight loss 
 
(2) To examine the history of brain injury (no TBI, single 
TBI, multiple TBI) in individuals with obesity as a 
possible factor in impulsive and compulsive eating. 
 
Hypothesis: TBI as a co-morbid condition may have 
some impact on eating behaviors. 
Research 
Intervention(s)/Investigational 
Agents 
tDCS (Starstim Noninvasive Wireless neurostimulator) 
IND/IDE # (if applicable) 
Class IIa device 
Study Population 
500 Veterans will be screened to enroll up to 50 
Veterans. Subjects will be recruited from Minneapolis 
VAMC’s Move Mass Behavior Modification Classes 
Sample Size (number of 
participants) 
20 (10 will undergo tDCS and 10 will undergo sham 
procedure). All will undergo Brain HQ task training to 
enhance executive function. 
Study Duration for Individual 
Participants 
About 3-4 months 
 
 
 

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2.  Abstract 
 
Objectives. Impulsivity and compulsivity are two psychological factors which contribute 
to addictive behaviors. Impulsivity is characterized by lack of foresight and planning, and 
excessive risk taking. Impulsivity is a characteristic of poor executive functioning, reflective of 
deficits in goal-oriented behavior and self-regulation. Impulsivity is common to a number of 
psychiatric conditions which contribute to high morbidity and mortality in Veterans such as 
substance abuse disorders, post-traumatic stress disorder, and traumatic brain injury (TBI). 
Impulsivity has been implicated in refractory obesity, in both bariatric and non-bariatric subjects 
(Sutin 2011, Filbey 2017, Gunstad 2017, Galioto 2016). Individuals with food impulsivity report 
out of control eating; they may report binging and/or cravings. Compulsivity, characterized by 
inability to break old habitual behaviors, may also play a role in refractory obesity. Transcranial 
direct current stimulation (tDCS) has been shown in other settings to reduce impulsivity. 
Coupled with brain training tasks to strengthen key circuitry involved in impulse control, the 
prefrontal cortex, tDCS has the potential to reduce impulsivity and compulsivity in individuals 
with obesity, with the potential for therapeutic application as a non-pharmacologic treatment for 
obesity in individuals with food impulsivity. 
Research plan and methods. We plan to enroll up to 50 individuals and complete 
studies in 20 individuals involved with the Minneapolis VAMC’s Move Mass weight management 
clinic. Participants, who report that they tend to have out-of-control eating at least once per 
week, will be randomized to either active or sham tDCS, two 13-minute sessions separated by 
20 minutes, for five consecutive treatment days; both groups will undergo brain training tasks 
during the treatments. After they complete the sessions subjects will complete a 16-week long 
structured Move Mass Behavior Modification program (usual care). In addition to the brain 
training tasks during the stimulation periods, subjects will complete a food-impulsivity related 
questionnaire (the Binge Eating Scale [BES]) and other instruments at several timepoints during 
the study. The effect of the active vs. sham treatment to reduce measures of impulsivity and 
improve measures of executive function will be assessed over time. As a secondary aim we will 
evaluate treatment effect on weight loss and examine the possible relationship to TBI. 
Clinical relevance. Refractory obesity, like other conditions with an addictive 
component, is in part related to impulsivity and inability to change compulsive behavior. More 
effective treatments are needed for this condition which significantly impacts morbidity and 
mortality in Veterans and non-Veterans. Safer, more effective treatments, including non-
pharmacologic treatments which make use of the brain’s own neuroplasticity to enhance 
function and heal or strengthen regions involved in impulse control represents an exciting new 
therapy for impulse control in individuals with obesity. 
 

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3.  Objectives and Specific Aims 
a. 
Purpose: The primary purpose of this study is to determine if tDCS coupled with 
executive function training decreases impulsivity and compulsivity in individuals 
with obesity.  As a secondary aim, we will evaluate whether tDCS when coupled 
with executive functions training enhances weight loss in individuals with obesity 
attempting to lose weight in a structured behavior-modification based program. 
b. 
Our specific aims are as follows: 
i. Aim 1: To determine if tDCS with executive function tasks vs. sham 
paired with executive function tasks reduces impulsivity and compulsivity 
in individuals who report out of control eating and are enrolled in a 16 
week structured behavior modification-based weight loss program 
ii. Hypothesis 1: tDCS treatment decreases impulsivity and compulsivity in 
individuals with obesity who are enrolled in a structured behavioral 
modification weight loss program. 
 
iii. Aim 2 (secondary): To test whether tDCS treatment, paired with 
executive function tasks, enhances weight loss compared to sham paired 
with executive function tasks in individuals who report out of control 
eating and are enrolled in a 16-week structured behavior modification-
based weight loss program 
iv. Hypothesis 2: tDCS treatment with executive functions training enhances 
weight loss in individuals with obesity who are enrolled in a structured 
behavioral modification weight loss program. 
v. Aim 3: To examine the history of brain injury (no TBI, single TBI, multiple 
TBI) in individuals with obesity as a possible factor in impulsive and 
compulsive eating. 
 
vi. Hypothesis3: TBI as a co-morbid condition may have some impact on 
eating behaviors. 
In addition to the hypotheses and aims above, we intend to confirm the findings of 
Galioto et al, and demonstrate that baseline executive function predicts weight loss 
success (Galioto 2016). 
 
4.  Background, Significance, and Preliminary Data 
 
Impulsivity and compulsivity are two psychological factors which contribute to addictive 
behaviors. Impulsivity is characterized by lack of foresight and planning, and excessive risk 
taking. Impulsivity is a characteristic of poor executive functioning, reflective of deficits in goal-
oriented behavior and self-regulation. Impulsivity is common to a number of psychiatric 
conditions which contribute to high morbidity and mortality in Veterans such as substance abuse 
disorders, post-traumatic stress disorder and TBI. Impulsivity has been implicated in refractory 
obesity, in both bariatric and non-bariatric subjects (Sutin 2011, Filbey 2017, Gunstad 2017, 
Galioto 2016). Individuals with food impulsivity report out of control eating; they may report 

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binging and/or cravings. Compulsivity, characterized by inability to break old habitual behaviors, 
may also play a role in refractory obesity. 
In our own experience with a non-veteran population followed in the Adult Medical 
Weight Management Clinic at the University of Minnesota where the average BMI is around 40, 
89% of patients self-reported some level of out of control eating and/or craving at intake 
assessment (manuscript in preparation by PI). With regards to the veteran population at the 
Minneapolis VA, a large percentage of patients also report cravings for particular foods, binging, 
or out of control eating. It is also of note that insight into the underlying neurobiology of food 
impulsivity and/or cravings can also inform understanding of other compulsive, addictive 
behaviors such as gambling, and drug addictions including alcohol and cocaine abuse. These 
disorders manifest out of common neurobiological soil, a lack of impulse control. 
Neurobiology underlying food impulsivity/cravings, and impulsivity. Eating and appetite 
behaviors are the output of brain networks comprised of homeostatic, reward and executive 
function components. Homeostatic appetitive centers in the brain include the hypothalamus, 
including the paraventricular (PVN), Arcuate, lateral, and dorsomedial nuclei. Traditionally, the 
hypothalamus has been considered an important region for acute and chronic fuel storage 
sensing, the basis for its homeostatic component to weight regulation. Other important 
components, brain reward centers, include the central nucleus of the amygdala, the nucleus 
accumbens, and the nucleus tractus solitaries which respond to other cues such as palatability; 
these limbic areas may also be affected by other non-homeostatic inputs such as emotions. 
Brain reward centers are strongly involved in mediating impulsivity- and compulsivity-related 
behaviors such as addictions, especially when these areas are not able to be adequately 
regulated by areas involved in executive function such as the prefrontal cortex. 
Inadequate “Gate-keeping”: Executive function and Obesity. Areas of the brain involved 
in directing goal-oriented behavior, such as the prefrontal cortex, provide an important counter-
balance to the activity of the brain reward centers, not only with regards to the impulse control 
involved in drug addictions but also with weight regulation. Executive function predicts weight 
loss success in structured medical weight loss programs (Galioto 2016). Ultimately it is the 
integrative interaction between and among the homeostatic, reward, and “gate-keeping” regions 
that determines appetite perception and response to it. There is no effective treatment for 
impulsivity. The ideal treatment would provide enhancement of function in areas of the brain 
which govern impulse control and may provide an important, under-appreciated target for 
obesity treatment. 
One common factor to both obesity and executive dysfunction is traumatic brain injury 
(TBI). Survivors recovering from TBI are at risk for obesity and overweight problems and health 
conditions, particularly during long-term recovery (Dreer et al., 2017). Dreer et al. (2017) 
showed increased prevalence rates of obesity immediately following and with increasing time 
since injury. Both TBI and obesity have negative consequences on frontal cortical structure and 
function. Obesity has been associated with atrophy in frontal lobes, with concomitant impaired 
performance on cognitive testing (Fotuhi & Lubinski, 2013). Cognitive dysfunction, in the 
domains of attention, impulsivity, and executive function, is a leading cause of disability 
following TBI (Rabinowitz & Levin, 2014; Wood & McHugh, 2013). Thus, the relationship 
between obesity and TBI, and their effects on impulsive behavior, are important to consider with 
regard to identifying factors related to unhealthy weight management and the design of 
treatment programs. 
Cognitive training coupled with transcranial direct current stimulation for impulsivity. 
1. Cognitive training for reducing impulsivity in healthy subjects. The go/no-go task has been 
utilized successfully to reduce chocolate eating in female undergraduates with chocolate craving 
(Houben/Jansen 2011) and beer consumption in heavy alcohol drinkers 

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(Houben/Nederkoom/Wiers/Jansen 2011) in very short-term studies. While there is evidence 
that cognitive training may provide potential treatment for impulsivity, with application to obesity 
management, there is concern that the results from very task-specific cognitive training may not 
generalize to other desirable behavior change. Unfortunately, cognitive training can be time 
consuming and in addition to lack of generalization, results of cognitive training may not persist.  
2. tDCS: A tool for reduction of impulsivity and compulsivity. tDCS, even in a single session, has 
been found to reduce cravings and enhance cue response to negative stimuli in individuals with 
alcohol use disorder (Boggio 2008). Furthermore, a multiple treatment schedule of tDCS (twice 
daily for 5 days) was found to help reduce relapse over a 6-month period in subjects with 
alcohol use disorder (Klauss 2014). Some investigators have found decreased cravings, as 
measured by questionnaires, after 5 days of treatment and 30 days later (Ljubisavljevic 2016). 
In preliminary data from members of our team tDCS over the dorsolateral prefrontal cortex was 
shown to reduce risk-taking impulsivity (see Preliminary Data section below). 
3. Cognitive training with tDCS: complementary therapy to strengthen circuitry deficits which 
underlie impulsivity and compulsivity, a tool for augmentation of neuroplasticity. Application of 
tDCS with relevant task-based cognitive training may enhance the function of pathways being 
stimulated by the task training (Bikson/Rahman 2013). Coupling of tDCS with a broader array of 
task training, rather than narrow domain-specific component of executive function, may allow for 
generalization of enhanced executive function and better long term therapeutic results for 
impulsivity-related disorders, including substance abuse and obesity. 
 
 
Significance. If tDCS can be utilized to enhance plasticity in regions of the brain 
involved in impulsivity and compulsivity, then tDCS combined with cognitive training becomes a 
powerful non-pharmacologic tool for altering brain circuitry to improve impulsivity and 
compulsivity.   This approach has the potential to be applied to a wide range of neurobiological 
disorders. 
 
Preliminary data. Prior work by members of our group demonstrates that the 
application of tDCS does appear to improve impulse control when applied with tasks which 
engage regions of the brain involved in executive function. Lim and colleagues conducted a VA-
based study in 30 individuals who underwent two 25-minute sessions (active tDCS vs. sham 
procedure coupled with performance of the Balloon Analogue Risk Task [BART]) for five days 
followed by sessions at one and two months. Subjects completed questionnaires and behavioral 
tasks measuring impulsivity (the Risk Task) before and after the intervention. After receiving 
active tDCS, subjects showed a significant 46% decrease in risky choice in the Risk Task from 
pre- to post-intervention, which persisted through the one and two-month follow-up sessions. 
The sham tDCS group showed no significant change in risky choice from pre- to post-
intervention.  
 
 
4.  Study Endpoints 
Primary Endpoint: decrease in impulsivity and compulsivity (as measured by 
change in NIH Examiner Score) with active tDCS compared to sham 
Secondary Endpoint: change in weight over the study period 
 

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5.  Study Intervention(s)/Investigational Agent(s) 
a. 
Description: tDCS and discussion of device handling. We will use the 
Neuroelectrics Starstim system, a wireless multichannel transcranial current 
stimulator. Periods of tDCS stimulation of 13 minutes will be twice a day, separated 
by 20 minutes (Monte-Silva et al., 2013), for five consecutive days (10 total tDCS 
stimulation sessions). Active tDCS: A 2-mA current will be administered via two 
circular carbon rubber core electrodes in saline-soaked surface sponges (25 cm2), 
placed in a neoprene headcap with marked locations based on the 10-10 EEG 
system. The anodal stimulating electrode will be at location F4, over right 
dorsolateral prefrontal cortex (DLPFC) and cathodal electrode at location F3, over 
left DLPFC. Sham tDCS: For sham stimulation, the electrodes will be placed at the 
same positions as for active stimulation (F3 and F4), but current will be ramped 
down immediately after the initial 30 s ramp up period. Thus, participants will feel 
the initial itching sensation associated with tDCS but will receive no active current 
for the rest of the stimulation period. This method of sham stimulation has been 
shown to be reliable (Gandiga, Hummel, & Cohen, 2006). The Starstim software 
supports the measurement of electrode impedance. Before each training session, 
the impedance of the electrodes will be checked and verified to be ≤10 KOhm. 
During a training session, the impedance is measured every second and if found to 
be > 20 KOhm stimulation will be terminated for safety. The current and impedance 
will be recorded for every session.  
b. 
IND/IDE: The FDA has classified this as a NSR device (an FDA letter for use of 
this same device in another study by members of our research team for a similar 
purpose and protocol is included with our IRB packet for this current application) 
 
6. Study Methods, Procedures, and Statistical Plan 
Study Design:  
For this single-site pilot study our statistical approach will be similar to prior work done by 
members of our team previously, a double-blind, randomized controlled design with participants 
randomized to either active or sham tDCS. For this study Veterans will be referred as potential 
candidates because they have obesity and self-report that they tend to have at least one 
occasion of out-of-control eating per week on average. Participants will be trained on the Brain 
HQ, an interactive computer software package in which subjects work through a series of 
structured exercises designed to stimulate neuroplasticity. Participants will be randomly 
assigned to receive either active tDCS or sham stimulation with their training during one hour 
session each day( 13 minutes of stimulation , 20 minute stimulation break, followed by 13 more 
minutes of stimulation) over five days. A 2 mA current will be applied with two 25 cm2 saline 
soaked electrode sponges with anode at F4 (right) and cathode at F3 (left) concurrent with the 
Brain HQ. To evaluate generalization, an untrained NIH Examiner Battery sub-set testing 4 
modalities of executive function will be performed before and after the five days of training. 
Subjects will then go through the Move Mass Behavior Modification after completing the five 
days of treatment. (This 16-week structured behavior modification program of bi-weekly 
sessions is usual care for these participants.) Participants will return for the trained and 
untrained testing at V7 (halfway through the  behavior modification course) and V8 (final study 
visit to occur after the behavior modification course) follow-up sessions without stimulation. For 
the trained Brain HQ tasks, growth curve analysis (GCA) examining individual variation of the 

8 
 
growth rates over time will be done (across the 5 days of tDCS sessions and the subsequent 
follow-ups) to examine for change in individual and group trajectories over time. For the 
untrained NIH Examiner tasks, GCA will be used to evaluate for individual and group effects in 
executive function in the four domains of the NIH Examiner Battery from pre- to post-treatment 
and through follow-up sessions. We will also compare pre- and post- treatment results in the 
cravings and binging questionnaires within and between groups. 
 
Figure 1: Study Visit Schedule  
 
 
 
 
 
 
 
 
 
 
 
Study Subjects: 
Potential subjects identified at the Minneapolis VAMC’s MOVE Mass Medical Weight 
Management Clinic where Drs. Sibley and Billington attend will be recruited into this 18-week 
clinical intervention using tDCS. The MOVE Mass Clinic at Minneapolis has a long history, 
having been established more than 30 years ago and having served as a prototype for the 
MOVE National Program. Flyers and/or posters will be posted throughout the Minneapolis VA 
facility and study staff will also present the study to other VA staff during team meetings and via 
emails to clinicians regarding recruitment. Letters may also be sent out to potential research 
patients. 
Inclusion criteria: 
Obese (BMI>30) 
Adults, ages 18 years or older 
Able to understand English, self-consent and follow study-related procedures 
Willing to use a reliable form of birth control if they are of females of child-bearing potential 
Exclusion criteria: 
History of any of the following: seizures, severe or moderate head injury, head surgery, 
significant neurological disorder(significance based on Principal Investigator’s judgment), 
frequent severe headaches, history of scalp conditions such as eczema or seborrheic 
dermatitis, metal in head (other than in mouth) including shrapnel/surgical clips/welding 
fragments, implanted medical devices (including pumps and cardiac pacemakers), pregnancy, 
active substance abuse, psychological or medical disorders requiring inpatient treatment, 
presence of a known metabolic or hormonal disorder (such as Cushing’s) which affects weight. 
History of hypothyroidism is acceptable if subject is on treatment with normal TSH and FT4 on 
most recent check within the last 3 months and has been on stable dosage of l-thyroxine for at 
least 3 months, taking it as prescribed. 
 
Subjects will be allowed to participate in the study if they are on obesity medications. It is 
recommended that patients do not adjust obesity medications once they have enrolled in the 
study, but if they need to stop or adjust medications due side effects, it will be documented on a 
medication review form that will be collected at each visit.   
 V1 
V2 V3 V4 V5 V6                                         V7                          
V8  
5 consecutive      
days 
8 weeks 
0-4 weeks 
8 weeks 
16-week Behavioral Modification program 

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Study Procedures: 
Five hundred individuals will be screened with the goal of consenting 50 patients and 20 
patients completing the study. The study consists of 8 study visits including 4 testing days, one 
before (V2) and one on the day of the fifth session of tDCS (V6) followed by the structured 16-
week long behavior modification class, and test visit half way through the 16-week class (V7) (2 
months into the behavior modification class), and a final test visit 2 months later (+/- 2 weeks) 
(V8). At consent/screening visit (V1), baseline serum biochemistries, a general physical 
(including weight measurement) pregnancy test, impulsivity questionnaire (Binge Eating Scale 
[BES], depression screening (PHQ-9 [https://patient.info/doctor/patient-health-questionnaire-
phq-9]), Minnesota Blast Exposure Screening Tool (MN-BEST), and executive function-related 
testing (NIH Examiner and Brain HQ) will be performed; these can be completed at V2 if those 
were not completed after consent on V1. These tests; other than the pregnancy, biochemistries, 
and PHQ-9; are repeated at V6-V8. While subjects are undergoing the 5 days of tDCS 
treatments (V2-V6) they will undergo Brain HQ testing during the treatment sessions. PHQ-9 is 
repeated at the final visit. 
Study Visit Details: 
Screening visit (Visit 1 [V1]): 
Subjects will be recruited from the clinic where Drs. Billington and Sibley attend. Interested 
subjects will be screened for inclusion/exclusion criteria and review study details. Medical 
records will be reviewed for eligibility, and interested subjects will be consented if they are 
eligible. They will then undergo baseline blood draw (to include a comprehensive metabolic 
panel if not available within last 6 months, directed history and physical (including a weight 
measurement). If thyroid tests, (TSH alone or a TSH with a free T4), were not done and normal 
in the last 3 months for individuals taking thyroid hormone replacement, these will be done at 
baseline assessment. Baseline testing including the NIH Examiner Battery (which measures 
executive function domains), MN-BEST and BES (may either be done at the end of V1 or 
beginning of V2). 
 
tDCS session visits (V2-6): 
Subjects will go to the Minneapolis VAMC GRECC where they will undergo the tDCS sessions.  
Subjects will be randomly assigned to active vs. sham treatments which will occur on 5 
sequential weekdays. The tDCS session will include a pre/post symptom rating questionnaire, 
13 minutes of stimulation, a 20-minute stimulation break, followed by 13 more minutes of 
stimulation.  Subjects will complete the Brain HQ test during stimulation and the stimulation 
break. The final stimulation visit, V6 will include NIH Examiner and their weight will be collected.  
These sessions will last around 1 hour to 1.5 hours each. 
 
Visits post tDCS intervention (V7 and V8): 
These visits will be identical to V1 with the exceptions that the history and physical, MN-BEST 
and blood draw will not be repeated; a weight measurement will be taken along with completion 
of the BES questionnaire, the Brain HQ and NIH Examiner. A short blinding questionnaire will 
be asked at V8 to assess the adequacy of tDCS blinding.  
 
Table 1. Table of Assessments 

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Visit 
Assessments 
Stimulation 
Duration 
Compensation 
Visit 1 
HIPAA, Consent, NIH Examiner, 
BES, PHQ-9, Medication Review, 
MN-BEST, Blood Draw, Physical 
(Weight Measurement), Pregnancy 
Test (if applicable) 
None 
120 minutes 
$30 
Visit 2-5 
tDCS, Pre/Post SRQ, Brain HQ, 
Medication Review 
tDCS 
60 minutes 
$15 
Visit 6 
tDCS, Pre/Post SRQ, Brain HQ, NIH 
Examiner, Medication Review, 
Weight Measurement 
tDCS 
90 minutes  
$22.50 
Visit 7-8 
(follow-ups) 
NIH Examiner, Medication Review, 
Brain HQ, BES, Weight 
Measurement,  
Visit 8 only: PHQ-9, Blinding 
Questionnaire 
None 
120 minutes 
$30 
                                                                                        Total: 
11.5 hours 
$ 172.50 
 
tDCS Device: We will use the Neuroelectrics Starstim system, a wireless multichannel 
transcranial current stimulator. Periods of tDCS stimulation of 13 minutes will be twice a day, 
separated by 20 minutes, for five consecutive days (5 total tDCS stimulation sessions). Active 
tDCS: A 2-mA current will be administered via two circular carbon rubber core electrodes in 
saline-soaked surface sponges (25 cm2), placed in a neoprene headcap with marked locations 
based on the 10-10 EEG system. The anodal stimulating electrode will be at location F4, over 
right dorsolateral prefrontal cortex (DLPFC) and cathodal electrode at location F3, over left 
DLPFC.This tDCS configuration has been shown to be effective for stimulating DLPFC. Sham 
tDCS: For sham stimulation, the electrodes will be placed at the same positions as for active 
stimulation (F3 and F4), but current will be ramped down immediately after the initial 30 s ramp 
up period. Thus, participants will feel the initial itching sensation associated with tDCS but will 
receive no active current for the rest of the stimulation period. This method of sham stimulation 
has been shown to be reliable (Gandiga, Hummel, & Cohen, 2006). The Starstim software 
supports the measurement of electrode impedance. Before each training session, the 
impedance of the electrodes will be checked and verified to be ≤10 KOhm. During a training 

11 
 
session, the impedance is measured every second and if found to be > 20 KOhm stimulation 
will be terminated for safety. The current and impedance will be recorded for every session. 
 
Computerized cognitive training during the tDCS or sham sessions: We will utilize Brain HQ 
Cognitive Training software (www.brainhq.com). 
 
 
Untrained tests (to evaluate for generalization at the beginning and end of the study): 
As done by Galioto and predictive of weight loss success in individuals with obesity (Galioto 
2016), we will utilize four components of the NIH EXAMINER battery, a validated computerized 
battery of experimental tests to assess four domains of executive function before and after the 
weight loss period. 
Domains: 
a. Working memory 
The Dot Counting Test.  Subjects will count and remember the number of blue circles in a 
display of other shapes. There are six trials in which the number of displays presented in each 
trial increases from two to seven. Participants are instructed to recall, in order, the total number 
of blue circles on each display and the correct responses are recorded. 
b. Inhibition 
The Flanker test. Subjects must make rapid decisions about the direction of central stimuli when 
surrounding items are congruent, pointed in the same direction or incongruent, pointed in the 
opposite direction. Lower scores on this domain are related to poor impulse control. 
c. Set shifting 
The Set Shifting task. A stimulus at the time of the screen must be matched to either of two 
stimuli in the corner of the screen on one of two types of characteristics (color and shape). The 
matching characteristic alternates in a pseudorandom fashion. Cognitive flexibility is evaluated 
with this task. Lower scores on this domain are related to greater behavioral compulsivity. 
d. Planning 
The Unstructured Task. A number of simple puzzles are completed, with differing point 
assignments (high and low value puzzles).  Subjects must plan the order in which they do the 
puzzles to obtain as many points as possible in 6 minutes. Puzzles with various assigned point 
values in order to obtain as many points as they can in 6 minutes. 
 
Other instruments: 
a. PHQ-9 
Mood will also be assessed at the beginning and end of the study. 
The Patient Health Questionnaire. The PHQ-9 will be used to assess nine DMS-IV-TR 
criteria for depression. Scores range from 0 to 27 with higher scores being consistent with more 
depressive symptoms. 
b. Binge Eating Scale (to be done at the same timepoints as the untrained cognitive testing)- 
The BES is a 16-item questionnaire assessing the presence of binge eating behaviors. The 
questions are presented as groups of statements about behavior, thoughts, and emotional 
states. Individuals indicate which statement in each group best describes how they feel. Higher 
scores are consistent with more binging behavior. 
c.Minnesota Blast Exposure Screening Tool (MN-BEST) 
The MN-BEST is a semi-structured interview to collect self-reported information. Using the 
instrument, the three most significant blast exposure events will be recorded in addition to the 
frequency and duration of post concussive symptomatology. A similar appraisal will be made of 

12 
 
the three most significant impact head injuries for the person in their lifetime. This information 
will then be used to make determinations about the presence of TBI from the events. 
d. Blinding Questionnaire  
The blinding questionnaire is a short, 3 question assessment administered by research staff at 
the end of study participation. The purpose of the questionnaire to assess the adequacy of 
tDCS blinding.  
 
 
 
Statistical Plan and Power Analysis 
 
For this pilot study our statistical approach will be similar to prior work done by members 
of our team, a randomized controlled design with participants randomized to either active or 
sham tDCS.  
Power Analysis.  For Aim 1, the primary comparison will be difference in change before 
and after training on untrained impulsivity-related tests of executive functioning between active 
and sham tDCS. Lim and colleagues’ preliminary data found an effect size of d=.97 between 
active and sham tDCS groups. Based on these results, the current pilot project is powered to 
detect an effect size of .97 with 80% power and an alpha = .05 (N = 20). Power to detect a 
medium effect size will be approximately .60. Thus, this study is well-powered to detect changes 
on the primary cognitive outcome variables. 
For the secondary aim of weight loss, an ANOVA will be used with weight as the dependent 
variable and the grouping variable will be active vs. sham. We will be testing for a Group x Time 
interaction for weight. 
 
 
7. Sharing of Results with Participants 
Subjects will receive a copy of the laboratory screening done at study entry and asked to follow 
up with their primary care providers further to discussion of those results. 
8. Study Duration 
Individuals will be in the study for about 3-4 months each. We anticipate screening 500 subjects 
to enroll 50 for this protocol over 12-14 months. The duration anticipated to complete all study 
procedures and data analysis is expected to be 6 months after the last subject is enrolled; the 
study duration for the entire study is expected to be about 2 years. 
 
9. 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 

13 
 
☐ Non-English speakers 
☐ Those unable to read (illiterate) 
☐ Employees of the researcher 
☐ Students of the researcher 
☒ None of the above 
Adults must have the capacity to self-consent to be in this study. 
 
10. Recruitment Methods 
a. 
Recruitment Process: Subjects will be approached in person by Co-investigators 
Sibley or Billington when they present for Move Mass appointments and will be 
directed to call the Study Coordinator for more study details and to set up their 
consent visit.  Subjects may also self-identify after seeing posters or flyers posted 
in the Minneapolis VAMC facility and contact the investigator team. Subjects may 
also contact the study team after hearing about the study from other providers at 
the Minneapolis facility. Consenting will take place in a private setting at the 
Minneapolis VAMC. Subjects may take as long as needed to decide whether or not 
to participate once they have heard about the study-related details from the 
investigative team and study staff will emphasize the voluntary nature of 
participation and that whether or not a subject participates has no bearing on 
clinical care provided by the VAMC. 
b. 
Source of Participants and identification of potential participants: Subjects will be 
recruited from the Minneapolis VAMC and surrounding CBOC’s patient population 
via clinical contact with the study investigators, or by self-identification after seeing 
flyers/posters or after hearing about the study from their other providers at this 
facility.  Subjects who expressing interest in the study and appearing to meet the 
eligibility criteria and agreeing to medical record review for the purposes of this 
study will then have their medical records reviewed to further assess study 
eligibility. 
c. 
Payment:  
Due to the commitment of time, and the potential for transportation costs and lost 
wages due to participating, subjects will be compensated for their study 
participation at a rate of $15 per hour.  If a subject completes only part of a visit 
they will be compensated at a rate of $10 per hour, prorated for the time spent in 
that visit. 
11. Withdrawal of Participants 
a. 
Withdrawal Circumstances: Subjects are free to withdraw from the study at any 
time and they may be withdrawn by the study investigators if it is deemed that it 
would not be safe for them to continue with the study or if subjects are not 
following the study-related procedures which would compromise the scientific 
integrity of the study. 

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b. 
Withdrawal and Termination Procedures: If a subject wishes to withdraw or is 
asked to withdraw from the study the participant would be asked to participate in 
an early end-of-study visit (procedures to be followed would be those of V8) and 
the subject would be asked about continued data collection of clinical data (vitals 
and medications) to finish out the period of time they would have participated in the 
study. All data collected up to the period of withdrawal or termination and as 
arranged with the subject through partial withdrawal would continue to be used as 
per study-related purposes. 
12. Risks to Participants 
a. 
Foreseeable Risks:  
Physical—tDCS is considered to be a safe brain stimulation modality which is 
rarely associated with adverse events and there is no evidence of serious side 
effects. Subjects will be discontinued from the study if they develop sores at the 
administration site or headaches which impair global functioning. Milder side 
effects that subjects could experience include itching at the site, nausea, milder 
headaches, and fatigue.  Subjects may choose to discontinue stimulation at the 
session at any time they experience discomfort or side effects. We will be utilizing 
the standards which have been utilized previously for this modality; trained study 
staff will administer the treatment sessions. 
Psychological—Questionnaires as well as the tDCS active vs. sham treatments are 
utilized during the visits; subjects could experience mental fatigue related to the 
testing. 
Social—there is no anticipated social risk to participating. 
Economic—Subjects could incur financial risks related to transportation and lost 
wages while participating; for this reason, study compensation is provided to help 
minimize this risk. 
Legal-- there is no anticipated legal risk to participating 
13. Potential Benefits to Participants and Society 
Potential Benefits: There is not potential for direct benefit other than as related to a 
decrease in food impulsivity but there is no guarantee of direct benefit.  Societal 
benefits could include providing better treatment for conditions related to 
impulsivity. 
14. Data Management 
 
Data Analysis Plan: For this pilot study participants will be randomized to either 
active or sham tDCS. For the trained task, growth curve analysis (GCA) examining 
individual variation of the growth rates over time will be done (across all 10 tDCS 
sessions and the subsequent follow-ups) to examine for change in individual 
trajectories over time. For the untrained task (NIH Examiner), GCA to evaluate for 
enhancement of executive function in the four domains from pre- to post-treatment 
as compared with the sham group will be analyzed. As a secondary aim we will 
evaluate weight loss response during and after the behavior modification program 

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and evaluate the effect of active vs. sham treatment on weight loss. Results from 
this study will inform larger follow up studies supported by external applications. 
15. Data security 
All PHI will be kept in a secure database behind the VA firewall. Any paper records will 
be stored in a locked file cabinet accessible to study staff only. Data from each subject 
will be assigned a unique study identifier with the key available only to study staff, stored 
in secure database behind the VA firewall. Patient identifiers may only be disclosed to 
the study’s finding entities for reporting and record keeping purposes as required by law. 
Any data that may leave the Minneapolis VAMC will be de-identified. 
16. Provisions to Monitor the Data to Ensure the Safety, privacy, and confidentiality of 
Participants 
Data privacy and confidentiality protection are described above. The study will also have 
an external study monitor, Catherine Niewoehner, MD, whose roles may include 
reviewing the study protocol and recruitment procedures with study staff, monitoring 
tDCS device utilization, and following up with any subjects and the IRB regarding any 
adverse events which occur. 
17. Discontinuation criteria 
● Sores at the tDCS site 
● Headaches that impair global functioning 
 
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