Neurologic Biomarkers of Smoking Behavior
Phase: PHASE2
Conditions: Smoking Cessation
Sponsor: University of Illinois at Chicago

 
 
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Neurologic Biomarkers of Smoking Behavior 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NCT 03811951 
Version: 9 
Date: 1/15/2019 
 

 
 
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1.0 
Project Summary/Abstract 
This program of research focuses on identifying neurologic biomarkers of smoking behavior in order 
to develop individualized smoking cessation aids. The research team has carefully designed the 
study protocol to ensure participant safety and confidentiality. This research will include 
administration of intranasal insulin and a placebo comparator. The intranasal insulin administered is 
an investigational drug and has been granted IND status by the FDA (IND#129432). During the times 
of drug effects, we will evaluate a biomarker using non-invasive equipment. Researchers are trained 
to be vigilant in identifying any side effects associated with the study drug and associated procedures. 
Anticipated risks of study drugs and equipment have been recognized by the research team and will 
be discussed as part of the informed consent process. Access to data collection and sensitive patient 
information will be limited to the Principal Investigator and designated research team. Researchers 
have quality control metrics in place to assure collection of accurate data, proper documentation of 
study activities, and predeveloped contingency plans in the event unanticipated problems occur.  
 
Schemas are welcomed and often provide a nice visual reference for the project: The proposed work 
is a 2-session crossover design study intended to evaluate the effects of intranasal insulin vs placebo 
in smokers and non-smokers. Study 
participants will be randomized to either 
receive Treatment A (intranasal insulin) or 
Treatment B (placebo) during each session 
(Figure 1). The washout period will be 1 week 
in duration. Study participants will consist of 
healthy smokers and healthy non-smokers. 
Period 1 represents the first testing session 
and Period 2 represents the second testing 
session. As discussed in the above-section, 
one specific treatment will be administered per 
session. 
 
 
2.0 Background/Scientific Rationale  
 
Describe the research problem and provide rationale for the research: Although there are several 
FDA-approved treatments for smoking cessation, only 6% of an estimated 40 million smokers 
successfully quit. Taking a more patient-specific approach to resolving this healthcare concern may 
lead to more efficacious outcomes. The purpose of finding a biomarker is to enhance future drug 
development of new smoking cessation pharmacotherapeutic agents. In addition to characterizing the 
biomarker, we will test whether intranasal insulin – an investigational drug – can improve go/no-go 
accuracy in smokers.  
 
Briefly summarize prior experience and/or history relevant to the research: The rationale for using 
intranasal insulin is its efficacy in relieving cognitive deficits as reviewed in several papers (Shemesh 
et. al., 2012, de la Monte 2013, Ott et. al., 2012, Reger and Craft 2006, Strachan 2005, Fehm 2000).  
Figure 1. Schema of the Proposed Study Design
 

 
 
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It is hypothesized that intranasal insulin will relieve cognitive dysfunction in smokers as shown in 
previous studies (Franken et al., 2010; Luijten et al., 2011b).  
 
Identify any investigational agents, drugs, devices, or biologics that will be administered or implanted 
into subjects: For this research study, smokers and non-smokers will be administered intranasal 
insulin (Novolin R, 60 IU) and placebo. Placebo will consist of sterile water with 14% NaCl. During 
administration of either intranasal insulin or placebo, participants will receive 1 spray in each nostril 
every 3 minutes for a total of 6 sprays. AeroPump delivers 0.1 ml of liquid per spray. Since the 
concentration of insulin in Novolin R is 100 IU/mL, six sprays will deliver the 60 IU dose.  
 
Summarize relevant preclinical data: See “Briefly summarize prior experience and/or history relevant 
to the research” (above).  
 
Summarize relevant clinical data to date: The clinical benefits of intranasal insulin administration have 
been elucidated in the context of cognitive dysfunction alleviation (Shemesh et. al., 2012). 
Accumulating evidence demonstrates that conditions such as diabetes and Alzheimer’s disease are 
associated with a deficiency of insulin signaling to the brain, resulting in cognitive impairment and 
decline. Such cognitive effects could be reversed or slowed with medical intervention to efficiently 
deliver insulin to the brain. Intranasal insulin administration is a noninvasive and efficient way to 
bypass the blood-brain barrier; thus, it may be a useful way to reintroduce insulin to the central 
nervous system to alleviate cognitive dysfunction caused by a hormonal deficit. 
 
Intranasally administered insulin has previously been shown to directly elicit changes in 
cognitive function with little impact on blood glucose levels (Kern et al., 1999). When insulin was 
administered intranasally to a cohort of healthy, euglycemic men, the dose administered was not 
significantly detectable from placebo by a change in blood glucose levels or cardiovascular activity. 
However, the treatment caused a significant reduction in the baseline-to-peak amplitude of the N1 
and P3 AEP components as well as an increase in P3 latency. These results indicate that intranasal 
insulin administration bypasses the bloodstream to directly impact the central nervous system. 
 
Intranasal insulin may also be a useful smoking cessation treatment, due to exploratory studies 
of its effects on craving in smokers (Hamidovic et al. 2017). Administration of intranasal insulin 
resulted in a lower self-reported urge to smoke and restored the cortisol response to experimentally 
induced stress. These results indicate that intranasal insulin may be an effective and viable smoking 
cessation product.  
 
Provide a rationale for the dosing or use of the device, risks to subjects, and potential benefits to 
subjects: We conducted two clinical trials with intranasal insulin (Hamidovic et al., 2017). The 60 
IU dose is identical as in those two studies (IND #116626 and IND# 120700). The first study (IND 
#116626), was a parallel-design clinical trial involving one-time administration of intranasal insulin (60 
IU) to smokers who were abstinent from smoking overnight. The second study (IND# 120700) was a 
36-hour crossover, inpatient hospital study in which smokers received two administrations of 
intranasal insulin (60 IU) on two separate days. None of the subjects in either of the two studies 
experienced hypoglycemia. Circulating glucose was not lower for the insulin group in comparison to 
the placebo group in either study. Olfactory function (measured with Sniffin’ Sticks (US Neurologics)) 
was no different between the insulin and placebo groups in both studies. Sniffin’ Sticks involves 
presentation of 12 different pens containing different smells. After the presentation of each pen, 

 
 
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participants complete a multiple-choice question with 4 possible choices; one of which is the answer 
corresponding to the correct smell. Local irritation was higher in the intranasal insulin group in 
comparison to the placebo group. Table 1 lists results of the Sniffin’ Sticks test, which measures the 
ability to correctly identify various smells. Table 2 lists the all the events reported in the study by 
treatment group in the IND#120700 study.  
 
Table 1. Summary of Sniffin’ Sticks (US 
Neurologics) Scores throughout the Study by 
Treatment for IND#120700 
 
Appointment 
Treatment 
Mean 
Std. Dev. 
Screening 
NA 
11 
0.80 
Session 1 
(day 1) 
Insulin 
11.29 
0.70 
Session 1 
(day 2) 
Insulin 
11.36 
0.61 
Session 2 
(day 1) 
Insulin 
10.9 
0.87 
Session 2 
(day 2) 
Insulin 
11.1 
0.78 
Session 1 
(day 1) 
Placebo 
10 
0.66 
Session 1 
(day 2) 
Placebo 
11.18 
0.83 
Session 2 
(day 1) 
Placebo 
11.40 
0.66 
Session 2 
(day 2) 
Placebo 
11.30 
0.64 
Follow-up 
Both 
11.25 
0.77 
 
Table 2. Adverse events reported by study participants.  
 
Event 
Number of 
occurrences 
during 
placebo 
treatment 
Number of 
occurrences 
during 
insulin 
treatment 
Number of 
occurrences 
reported at 
follow-up 
Nasal occurrences 
Rhinorrhea 
1 
1 
 
Irritation 
5 
7 
 
 
Other 
Dizziness 
 
1 
 
Sweating 
 
2 
 
Headache 
 
1 
 
Nonspecific pain 
 
 
2 
Visual disturbances 
 
 
1 
Confusion 
1 
2 
 
Tingling (mouth) 
 
1 
 
Shaking 
 
1 
1 
Anxiety 
1 
1 
 
Diarrhea 
 
 
1 
Restless 
 
1 
 
Uncomfortable 
 
1 
 
Watering eyes 
 
2 
 
Menorrhagia 
 
 
1 
Given the growing evidence that intranasal insulin prevents neuronal damage, reduces nicotine 
cravings (Hamidovic et al., 2017) and improves cognition in diabetes, stroke, postoperative cognitive 
dysfunction, developmental delay, Parkinson’s disease, bipolar disorder, Alzheimer’s disease and 
HIV-associated neurocognitive disorders (summarized in Nedelcovych et al., 2018), a recent study 
compared insulin exposure in mouse brain and plasma following intranasal and subcutaneous 
administration of 2.4 IU (Nedelcovych et al., 2018). Whereas the subcutaneous insulin achieved 
therapeutically relevant concentrations in the brain (AUCbrain= 2537 h·μ IU/mL), it dramatically 
increased plasma insulin (AUCplasma = 520 351 h·*μ IU/mL), resulting in severe hypoglycemia and 
in some cases death.  The intranasal administration of the same dose resulted in similar insulin levels 
in the brain (AUCbrain = 3442 h·μ IU/mL) but substantially lower plasma concentrations 
(AUCplasma  = 354 h·μ IU/mL), amounting to a ∼2000-fold increase in the AUCbrain:plasma ratio 
relative to SC. The intranasal dosing also had no significant effect on blood glucose. Intranasal insulin 
administration over 9 days increased brain glucose and energy metabolite concentrations (e.g., 
adenosine triphosphate and phosphocreatine) without causing overt toxicity, suggesting that 
intranasal insulin may be a safe therapeutic option. 
 
Based on the 60-kg human, the 2.4 IU/kg dose given in the Nedelcovych et al (2018) study 
converts to a 144 IU dose, which is above the 60 IU dose we plan to administer as a one-time dose in 
the proposed study. 
 

 
 
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3.0 
Objectives/Aims 
Identify hypotheses being tested/primary endpoints/primary purpose of the protocol: The aim of the 
proposed work is to evaluate go/no-go accuracy as a neurologic biomarker of smoking behavior. Our 
hypothesis is that following intranasal insulin administration, smokers will have an improved go/no-go 
accuracy.  
 
Study duration: This duration of the research study is 2 years starting January 2018 – January 2020. 
 
4.0 
Eligibility 
Identify the subject population being evaluated by the protocol: All study participants will be healthy 
volunteers. Out of the sample recruited for this research, two groups will be formed based on the 
smoking status: Healthy non-smokers and healthy smokers. The criteria to separate the two groups is 
listed in Section 4.1 Inclusion Criteria.  
 
Indicate the source of subjects: Study participants will be recruited from the general population using 
electronic media (ex: Craigslist), flyers, newspaper advertisements and word-of mouth referrals. 
 
Identify who will assess and determine subject eligibility: Research staff (postdoctoral fellow(s) and 
research coordinator(s)) will assess eligibility criteria based on a detailed flowsheet (i.e. checklist) 
created specifically for this study. All research staff will be trained by the PI on assessing 
inclusion/exclusion criteria. The record of this training will be kept on file in the PI’s laboratory. Study 
PI will sign off on all study participants who passed the screening session as the final approval of 
subject’s entry into the study. 
 
Indicate how and where eligibility will be documented: After completing each step of the flowsheet, 
the coordinator/postdoctoral research fellow will place time of completion and his/her initials. The PI 
will document approving participants for study participation on the flowsheet.  
 
Attach an eligibility checklist to the protocol: Eligibility will be documented on the “Session Flowsheet”, 
which is attached to this application. It is also listed in Sections 4.1 and 4.2 below.  
 
4.1 Inclusion Criteria 
 
• Age between 21-40 years 
• Smokers only: Smoke at least 10 cigarettes daily (verified by carbon monoxide 
concentrations greater than 10 ppm).  
• Non-smokers only: No self-reported cigarette use in the past 1-year period.  
• Non-smokers only: Carbon monoxide concentration < 6 ppm. 
• Normal vitals (blood pressure < 120/80 mmHg; heart rate between 60 and 100 bpm, body 
temperature <37 °C) 
• Point-of-care (POC) blood glucose between 70 and 140 mg/dL 
• Body mass index between 18.5 and 30 kg/m2 

 
 
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 4.2 Exclusion Criteria 
 
• Use of non-cigarette tobacco products, e-cigarettes, or smoking cessation treatment 
• Positive urine drug screen test 
• Current pregnancy (urine test-verified) or lactation, or a plan to become pregnant 
• Breath Alcohol Concentration >0.00% 
• Shipley IQ test <80 
• Hyposmic or anosmic individuals (identifying less than 10 of 12 smells correctly) 
• Abnormal physical exam of the nares 
• Lifetime DSM-5 Axis 1 disorder (except anxiety and depression)  
• Current DSM-5 Axis depression or anxiety disorder 
• Over-the-counter or prescription psychotropic medications (confirmed by PI upon 
screening) 
• Use of any medications administered intranasally  
• Allergies to any ingredients in intranasal insulin or placebo 
 
 
 
 
4.3 Excluded or Vulnerable Populations 
 
Describe specifically and state the justification for any vulnerable populations (i.e., minors) or any 
excluded populations (i.e., non-English speaking subjects): Vulnerable populations will not be 
included in the study. Participants who don’t speak English are not included in the study because the 
questionnaires and study instructions have been developed in the English language.  
 
5.0 
Subject Enrollment 
 
Describe screening and enrollment: The telephone number and email of the CEDAR lab will be 
included in the advertisement. Once participants contact the lab, they will complete an initial 
screening survey (please see document “Initial Survey”). Study participants will have the option of 
completing the survey either electronically (via REDCap link) or by calling in. In the case of a phone 
call, study coordinator will enter participant responses into REDCap for determination of eligibility. 
Participants passing the “Initial Survey” will be scheduled for an in-person screening. The document 
“Screening Flowsheet” outlines the procedures which will be completed at the in-person screening to 
determine eligibility as outlined in Section 4.1 and 4.2.  
 
Describe from where subjects will be recruited and any advertising or recruitment materials that will 
be used: Study participants will be recruited from the general population using electronic media (ex: 
Craigslist), flyers, newspaper advertisements and word-of mouth referrals. The advertising materials 
will include hard copy posters and Craigslist advertisement. Copies of both are attached to this 
application.  
 

 
 
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Describe what happens with screen failures and any data obtained from screen failures: Data 
gathered from participants failing the screening criteria will be kept with all study documentation, 
following which it will be shredded with the remaining study documentation. The reason the 
documentation will be kept is in the event the same subject returns with information different from 
what he/she reported previously. In this event, we will be able to compare responses and optimize 
subject protection and study integrity.  
 
Describe the methods to minimize coercion and undue influence on the subjects: The consent 
procedure is detailed according to processes established in the Code of Federal Regulation and 
University of Illinois Institutional Review Board. Each research coordinator and postdoctoral research 
fellow will be trained by the PI and will complete the checklist (included in the “Screening Flowsheet” 
document). Study participants will be given ample time to review the form. The consent procedure will 
be carried out in a private and quiet setting. Prior to initiating the procedure, the person consenting 
will ensure that the individual is adult, able to read and understands the English language. The most 
recent version of the consent form will be used. The individual obtaining the consent will summarize 
each section of the consent. Study participants will be told the following: “Take as much time as you 
need to read the entire consent form. Please inform me when you are done reading the form so I may 
answer any questions you have.” All the questions the subject had will be written on the coordinator 
flowsheet. The signed informed consent copy will be given to study participant.  
 
Describe the procedures to separate clinical responsibilities and influence from research 
responsibilities and influence: This research study does not recruit patients; hence, there are no 
clinical responsibilities.  
 
6.0 
Study Design and Procedures 
 
List any collaborating sites where human subjects research will be performed, and describe the role of 
those sites and collaborating investigators in performing the proposed research (if applicable): This 
study will be only conducted at University of Illinois. Study space will be rented at Center for Clinical 
and Translational Science. In addition, UIC nurse will be responsible for performing nasal 
examination and collecting blood samples. Study personnel – working out of the PI’s laboratory - will 
ensure regulatory compliance, recruit participants, as well as collect and analyze the data. The PI’s 
lab is located on the first floor of UIC College of Pharmacy. Study materials, equipment and all paper 
copies will be locked in the office of research staff affiliated with the study. 
 
Describe the study design. The description should be capable of meeting the study objectives: This is 
a two group, two session study. The only eligibility criteria separating the two groups is the smoking 
status, otherwise the study population will consist of healthy volunteers. Following successful 
completion of the “Initial Survey”, study participants will be scheduled for a 3-hr In-Person Screening 
visit. At the in-person screening, participants will 1. be consented, 2. provide urine and breath 
samples, 3. complete surveys, and 4. receive study instructions. After the completion of the “In-
Person Screening”, study participants will be scheduled for two study sessions, separated by a 
minimum of 1 week. During the study session, in random order, study participants will receive either 
intranasal insulin (60 IU) or placebo. This is a cross-over study –participants receiving intranasal 
insulin will receive placebo next, and vice-versa. Please refer to Table 1 for a summary of the study 

 
 
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session. The sessions will be identical, other than participants receiving intranasal insulin or placebo 
in random order.  
 
 
 
 

 
 
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6.1 
Procedures and Assessments  
 
Provide a thorough description of all study procedures, assessments and subject activities in a logical 
and sequential format. Indicate what study activities happen when and where, including, when 
applicable, a study schedule that notes number and length of study visits for subjects.  
 
Table 3. Outline of Study Session 
TIME 
PROCEDURE 
8:00-8:30 
Determination of session eligibility (urine and breath tests) 
8:30-8:50 
Nicotine gum break (smokers), generic chewing gum break (non-smokers)  
8:50-9:00 
Nicotine blood sample 
 
9:00-9:05 
POC glucose check 
9:05-9:15 
Nares exam 
9:15-10:00 
Relaxation phase (both smokers and non-smokers)  
10:00-10:06 
Spray administration 
10:10-10:30 
Equipment setup 
10:30-11:40 
Go-No/Go task 
11:40-11:45 
Olfactory function test 
11:45-12:00 
Discharge procedure (POC measurement) 
 
Study session will begin at 8:00 AM. First, the research coordinator will ensure that the lab has 
a signed consent form on file from the participant. Smokers will be instructed to smoke the normal 
amount of cigarettes they usually smoke upon waking prior to each session, then refrain from 
smoking until the end of the session. For example, if they usually smoke 2 cigarettes upon waking, 
they will be instructed to smoke 2 cigarettes prior to the first session (30 minutes upon waking) and 2 
cigarettes prior to the second session (30 minutes upon waking). Participants will be asked if they 
have had breakfast. If they did not eat breakfast that morning, research coordinator will give them a 
granola bar and re-emphasize the importance of eating breakfast. Next, from 8:00 AM to 8:30 AM, 
urine and breath samples will be obtained by the study coordinator, for verification of absence of 
alcohol intake. A urine sample will be obtained to rule out illicit drug intake and pregnancy. See 
Section 6.2 Specimen Considerations for more information on urine sample collection and analysis 
protocol. 

 
 
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At 8:30, smokers will take a 20-minute nicotine chewing gum (Nicorette gum, 4mg) break, and 
non-smokers will take a 20-minute generic, non-nicotine chewing gum break. As per the instructions 
given by Nicorette, smokers will be instructed chew the gum slowly until they experience a tingling 
sensation, then to place the gum between their cheek and gum until the tingle subsides and repeat 
until most of the tingle is undetectable. Non-smokers will be instructed to chew the generic gum at 
their own pace.  
At 8:50 AM, research coordinator will administer VANES Questionnaire on REDCap. Following 
completion of the VANES Questionnaire, a nicotine blood sample will be taken by the study nurse to 
ensure comparable nicotine levels in participants between the two sessions. In order to synchronize 
the procedure in both smokers and non-smokers, a blood sample will be taken from non-smokers as 
well.  
Point of care measurement will occur at 9:00, followed by a physical exam of the nares at 9:05. 
POC glucose will be checked to ensure normal glucose levels. Study nurse will be responsible for 
conducting nares physical examination. Subjects will relax from 9:15 to 10:00. The blood draw at 8:50 
(for the purpose of nicotine level analysis) can cause a rise in cortisol, which remains high for 
approximately 60 min. The purpose of the relaxation phase is to wait for the stress response to 
normalize, thereby minimizing its impact at the time of treatment administration and event related 
potential testing. 
Spray administration will occur at 10:00 AM as one spray in each nostril every 3 minutes for 
the total of 6 sprays (two sprays at 10:00, two sprays at 10:03, two sprays at 10:06). The same spray 
protocol will be followed for administration of both intranasal insulin and placebo. AeroPump delivers 
0.1 ml of liquid per spray. Since the concentration of insulin in Novolin R is 100 IU/mL, six sprays will 
deliver the 60 IU intranasal insulin dose. See Section 6.3 Drug Product Considerations for more 
information on insulin and placebo intranasal administration preparation.  
Computerized task testing will occur at 10:30. During the Go/No-Go task, study participants will 
be instructed to respond as “quickly and accurately as possible” with their right index finger every time 
the target (“Go”) stimulus (a white “X”) appears, and to withhold a response when the distracter 
“No/Go” stimuli (a white “K”) appears. Targets will appear with higher frequency (84%, 412 trials with 
206 for each run) than distractors (16%, 78 trials with 39 for each run) to establish a strong stimulus-
response mapping on “Go” trials. In the second task, visual stimuli will be presented every 1000 ms, 
each for 100 ms duration, for a total of 400 trials (divided into two 200 trial blocks, separated by a 30-
s break). The target stimulus will be a 3.5-cm diameter blue circle (presented 15% of trials), the 
standard stimulus wi ll be a 3.0-cm diameter blue circle (presented 70% of trials), and the distracter 
stimulus will be an 18-cm2 black and white checkerboard (presented 15% of trials). Participants will 
be instructed to respond via button press as quickly as possible to target stimuli using the index finger 
of their dominant hand.  
At 11:40 AM, the olfactory function test will be administered by a study coordinator. Olfactory 
function test will use the Sniffin’ Sticks protocol as outlined in Section 7.0 Expected Risks/Benefits. 
Discharge procedure will occur at 11:45 AM. Study participants will be given instructions for 
the next session (or will be provided assent document in the event this is the second session). Their 
POC glucose will be checked to ensure normal glucose levels. Section 11.0 “Data and Safety 
Monitoring” provides further details regarding implementation of safety measures in the study, and 
how potential cases of hypoglycemia will be handled. 
 

 
 
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Indicate which procedures are standard of care and which procedures are being done for research 
purposes: None of the procedures in this research study are standard of care. They are all being 
done for research purposes. 
 
6.2 
Specimen Considerations 
 
Describe the specimens to be collected: Urine drug specimens and blood samples will be collected 
from participants prior to screening and testing procedures. Urine specimens will be used to perform 
urine drug screens and pregnancy tests. Blood samples will be used to determine nicotine blood 
levels. Blood samples will also be used to monitor blood glucose levels during the study. 
 
Describe aliquoting and any plans for retention specimens: Samples will be collected at the UIC 
Center for Clinical and Translational Science. Blood specimens used for nicotine test will be 
transported to UIC Research Resources Center for analysis. Urine specimens and blood samples 
collected for POC glucose check will not undergo aliquoting or be retained for future use. 
 
Describe tracking and labeling system: The label (Figure 4) 
includes the information that will be on the urine collection cup 
during urine drug screen and urine pregnancy testing or on the 
blood sample collection vial during nicotine blood test. 
Researchers will document test results from urine screening on 
the study flowsheet. 
 
Describe where the specimens be stored and who will be 
responsible for care of specimens during storage: Urine 
specimens and blood samples will not be stored for future use. 
 
Describe how long the specimens will be kept: Urine specimens will be disposed immediately after 
drug and pregnancy screen. Blood samples used for POC blood glucose testing will be disposed 
immediately after blood glucose check. Following study completion, blood specimens for nicotine 
testing will be frozen at the UIC Center for Clinical and Translational Science for up to 6 months 
before transport on dry ice to UIC Research Resources Center. Urine drugs screens, pregnancy 
tests, and POC glucose checks are expected to take approximately 5 minutes each. 
 
Describe how specimens will be destroyed at study completion: Urine and blood specimens will not 
need to be retained by researchers until study completion. Urine specimen will only need to be 
collected for drug and pregnancy screen during the in-person screening and prior to both testing 
session. Following drug and pregnancy screen, all urine specimens will be disposed immediately as 
noted above. Following POC blood glucose check, all blood specimens will also be disposed 
immediately. Following study completion, blood specimens for nicotine testing will be stored and 
shipped to UIC Research Resources Center as noted above.  
 
Describe how specimens will be analyzed (type and state of development of assay, controls): The 
research team will conduct and analyze urine drug screens at the beginning of each testing session. 
The research team is equipped with supplies and has undergone training to perform urine drug 
Figure 4. Specimen Label 
 
 
 
 
 
 
 
 
Subject ID: ___________ 
Specimen: Urine/Blood 
 
FOR RESEARCH 
PURPOSES ONLY 
 

 
 
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screens and pregnancy screens. For the drug screening, participants will first be asked to provide a 
urine specimen. A member of the research team will verify the temperature strip on the collection cup 
is between 90 – 100°F. Researchers will immerse a 12-panel drug screen dipcard into the urine 
specimen for 10 seconds and analyze the results in 5 minutes. For pregnancy testing, researchers 
will immerse an HCG test strip into the urine specimen for 3 seconds and analyze results in 5 
minutes. Testing supplies used for drug and pregnancy screens are FDA approved with 
approximately 99% accuracy of test results.   
 
The research team will perform pregnancy testing using AccuMed HCG test strips by 
immersing the HCG test strip into the urine specimen for approximately 3 seconds and reading the 
results after 5 minutes. AccuMed HCG test strips are easy-to-use and provide quick and accurate test 
results. The test strips provide early pregnancy detection with HCG sensitivity levels as low as 25 
mIU/mL. This product is FDA approved and provides over 99% accuracy of results. 
 
Each POC blood glucose check will be conducted by a study nurse using the Accu-Check 
Performa glucometer. A glucose test strip will be inserted into the glucometer. The study nurse will 
then prick the participant’s finger with the lancing device and place the end of finger with the blood 
drop to the test strip. Blood glucose will be read by the meter and displayed within 5 seconds.   
 
6.3 Drug Product Considerations 
Name and description of product: The drug substance used for preparation of the final drug product 
will be bulk Novolin R. Novolin R is a sterile, clear, aqueous, and colorless solution that contains 
human insulin (rDNA origin) 100 units/mL, glycerol 16 mg/mL, metacresol 3 mg/mL, zinc chloride 
approximately 7 mcg/mL and water for injection. The pH is adjusted to 7.4. Hydrochloric acid 2N or 
sodium hydroxide 2N may be added to adjust pH. Novolin R vials are latex-free. The drug substance 
is being purchased from McKesson. The placebo utilized in this study is 14% sodium chloride in 
sterile water.  
 
Route of administration, dosing, dosage regimen and duration: Intranasal insulin will be prepared by 
University of Illinois Hospital and Health Sciences System Investigational Drug Service. The service is 
located in the Hospital Pharmacy and contains a segregated compounding area with a biological 
safety cabinet (BSC). The drug product will be compounded in the BSC using aseptic technique. The 
pharmacist or a pharmacy technician designee will prepare the requisite drug product following 
personnel hand hygiene and garbing procedures according to USP<797>.  Aero Pump nasal spray 
system is manufactured in ISO Class 7 environment, hence sterilization of the system prior to 
compounding procedure will not be necessary. Aero Pump and Novolin R vial will be placed into the 
BSC. A volume of 3.3 mL Novolin R will be withdrawn using a set of sterile needle and syringe 
followed by emptying the contents of the syringe into the AeroPump glass bottle. The bottle will then 
be capped with AeroPump nasal spray. Finally, sterile gauze will be sprayed with sterile IPA following 
which 20 sprays will be pumped into the gauze for the purpose of priming the final drug product.  
Placebo will be prepared using the aseptic technique as described for intranasal insulin. The 
pharmacist or a pharmacy technician designee will transfer 2.7 mL of sterile water and 4 mL of sterile 
23.4% NaCl solution into a sterile container with 10 mL capacity. A volume of 3.3 mL of 14% NaCl 

 
 
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solution will be aseptically placed in the Aeropump spray as describeda. The final step will be the 
same priming procedure as for insulin spray. 
The directions for spray administration will be one spray in each nostril every 3 minutes for the 
total of 6 sprays delivered over 6 minutes. AeroPump delivers 0.1 ml of liquid per spray. Since the 
concentration of insulin in Novolin R is 100 IU/mL, six sprays will deliver the 60 IU dose. Aero Pump 
and Novolin R vial will be placed into the BSC. A volume of 3.3 mL Novolin R will be withdrawn using 
a set of sterile needle and syringe followed by emptying the contents of the syringe into the 
AeroPump glass bottle. The bottle will then be capped with AeroPump nasal spray. Finally, sterile 
gauze will be sprayed with sterile IPA following which 20 sprays will be pumped into the gauze for the 
purpose of priming the final drug product.  
Placebo will be prepared using the aseptic technique as described in the above paragraph. 
The pharmacist or a pharmacy technician designee will transfer 2.7 mL of sterile water and 4 mL of 
sterile 23.4% NaCl solution into a sterile container with 10 mL capacity. A volume of 3.3 mL of 14% 
NaCl solution will be aseptically placed in the Aeropump spray as described in the “Drug Product” 
paragraph. The final step will be the same priming procedure as for insulin spray. 
 
Describe how any adverse events or serious adverse events will be handled: Section 11.0 describes 
in detail study procedures which will be implemented to 1. Ensure thorough and accurate collection of 
AEs and UPs, 2. Timely reporting to the Institutional Review Board, and 3. Follow-up and resolution 
of all potential AEs and UPs. 
 
List/describe the expected adverse events based on the product label: Expected adverse events from 
an investigational study conducted with intranasally administered Novolin R (IND#120700) are listed 
below: 
• Local (nasal): anosmia, nasal irritation, local tissue damage 
• Cognitive: confusion, visual disturbances 
• Others: sweating, shaking, hunger, tingling sensation around the mouth 
 
Expected adverse events from the product label for Nicorette gum are listed below (Nicorette 
Informational Pamphlet, 2017):  
• Central nervous system: Depression, dizziness, headache, insomnia, lack of concentration, 
nervousness, pain, paresthesia  
• Dermatologic: Diaphoresis 
• Gastrointestinal: Aphthous stomatitis, constipation, diarrhea, dysgeusia, dyspepsia, flatulence, 
gingival hemorrhage, glossitis, hiccups, nausea, sialorrhea, stomatitis, tooth enamel damage 
(abrasions), xerostomia 
• Dermatologic: Skin rash 
• Hypersensitivity: Hypersensitivity reaction 
• Local: Application site reaction, localized edema, localized erythema 
• Neuromuscular & skeletal: Arthralgia, jaw pain, myalgia 
• Respiratory: Cough, sinusitis 
 
7.0 
Expected Risks/Benefits  
 

 
 
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Include expected risks and benefits to subjects and/or society: There are no expected benefits to the 
participants of this research study, however, it is expected that a better understanding of biomarkers 
will lead to more sophisticated smoking cessation treatments.  
 
 
There may be side effects associated with placebo and intranasal insulin administration. One 
common side effect of placebo is nasal burning and irritation due to a high salt content. Based on the 
results of our earlier INDs with the same 60 IU dose of intranasal insulin, we don’t anticipate any risks 
of particular severity or seriousness. Nonetheless, as in our previous IND studies, we will complete a 
detailed evaluation of circulating glucose and olfactory function. Following each of the three rounds of 
administration, on a scale of 1-10, the following will be assessed: 1. Pain, 2. Burning, 3. Taste, 4. 
Cough and 5. Anything else participants wish to rate with regards to local irritation.  
 
To ensure that participants’ blood glucose levels are not adversely affected by intranasal 
insulin administration, we will measure blood glucose levels for an immediate glucose level reading to 
ensure that participants are not hypoglycemic. If a study subject tests below euglycemic level (<70 
mg/dL) at any point during the study, the session will be stopped and the subject will be treated. A 
hypoglycemic subject will be given 15 grams of glucose (4 oz of orange juice) and their glucose level 
will be rechecked in 15 minutes. The process will be repeated if they are still hypoglycemic. Once 
treated, they will be given a snack (a granola bar) to eat in order to prevent recurrence. Subjects will 
then engage in a light activity such as reading for an hour. Following this hour, subjects will drink 4 
ounces of orange juice and eat a granola bar. At this time, we will retest their blood glucose levels. 
Upon confirmation that the subject is still euglycemic, he/she will be discharged. 
 
To assess olfactory function, all subjects will undergo a baseline smell test, and only 
individuals with normal smell function (identifying 11 or 12 out of 12 total smells) will be eligible to 
participate in the study. Sniffin’ Sticks involves presentation of 12 different pens containing different 
smells. After the presentation of each pen, participants complete a multiple-choice question with 4 
possible choices; one of which is the answer corresponding to the correct smell.  
 
This research study involves risks to pregnant women and/ or an unborn baby which are 
currently unforeseeable.  To protect against possible side effects of nicotine, pregnant and nursing 
women will not be eligible to participate in the study. Pregnancy will be ruled out prior to initiating any 
of the two study sessions.  
 
Additionally, there is a potential risk of loss of confidentiality. Information that identifies subjects 
will only be shared between research staff involved in this particular study. The research team will 
make every effort to protect subject’s private health information and guard against any loss of privacy. 
Participant information will be securely stored and only accessible to authorized personnel as 
described in section 8.0 “Data Collection and Management Procedures”.  
 
Describe the expected frequency, degree of severity, and potential reversibility of the risks:  
 
As investigation of intranasal insulin effects on brain has gained considerable interest both in the 
United States and internationally, a group of authors (Schmid et al., 2018) recently conducted a 
systematic review on the safety of intranasal insulin. They identified thirty-eight studies, with the total 
of 1092 study participants with acute (i.e. one time) intranasal insulin application and 18 studies with 
chronic treatment lasting between 21 days and 9.7 years (total of 832 study participants). The authors 
listed all adverse events reported by study authors and noted that there were no cases of 
hypoglycemia or severe adverse events (Figure 3). 

 
 
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Figure 3. Adverse events of intranasal insulin identified by Schmid et al., 2018. 
 
 
 
 
 

 
 
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In a previous study on intranasal insulin (IND #120700), smokers received two administrations 
of intranasal insulin (60 IU) on two separate days. Table 2 (see Section 2.0 Background/Scientific 
Rationale) lists all the adverse events reported in the study by the treatment group. Common reported 
events included nasal occurrences such as rhinorrhea and irritation, which are to be expected given 
the exploratory nature of intranasal administration of Novolin R, which is designed for subcutaneous 
delivery. 
Single uses of nicotine chewing gum use can have nicotine-mediated cardiovascular effects, 
including an acute heart rate increase of up to 10-15 beats/min and a blood pressure increase of up 
to 5-10 mmHg (Benowitz et al., 1997). Both of these effects are similar to those of cigarette smoking 
as well as to other nicotine replacement therapies, such as intravenous nicotine and nicotine nasal 
spray.  
 
Describe any dose modifications as a result of adverse events, as applicable: Based on the results of 
our earlier INDs with the same 60 IU dose of intranasal insulin, we don’t anticipate any risks of 

 
 
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particular severity or seriousness. Nonetheless, as in our previous IND studies, we will complete a 
detailed evaluation of circulating glucose and olfactory function (see first subheading) and make the 
appropriate dose modifications if adverse events occur. 
  
 
8.0 
Data Collection and Management Procedures  
 
Outline the process for data procurement: Table 3 below lists data collection tools. The list of data 
collection materials attached to this application is after the reference section (14.0).  
 
Table 3. Data procurement layout for “Neurologic Biomarkers of Smoking Behavior” 
Data Collection Tool 
REDCap  
Hard copy 
Hard Drive 
Used for 
Determination of 
Study Eligibility 
1. 
Initial Survey 
 
 
 
 
2. 
Urine Drug Test Results  
 
 (Flowsheet) 
 
 
3. 
Urine Pregnancy Tests 
 
 (Flowsheet) 
 
 
4. 
Cigarette Smoking 
Quantity 
 
 
 
 
5. 
Carbon Monoxide Level 
 
 (Flowsheet) 
 
 
6. 
Breath Alcohol Level 
 
 (Flowsheet) 
 
 
7. 
Medication and Health 
Review 
 
 (Flowsheet) 
 
 
8. 
Mental Health Interview 
 
  
 
 
9. 
Hearing Test 
 
 (Flowsheet) 
 
 
10. Shipley IQ Test 
 
 (Flowsheet) 
 
 
11. Demographics Survey 
 
 
 
 
12. Substance Use Survey 
 
 
 
 
13. Visual Analog Nicotine 
Effects Scale (VANES) 
 
 
 
 
14. POC Glucose Level 
 
 (Flowsheet) 
 
 
15. Adverse Event 
Questionnaire  
 
 
 
 
16. Adverse Event Tracking 
Form 
 
 
 
 
17. Spray Effect Rating 
Questionnaire  
 
 
 
 
  
The mental health document includes a question about suicide risk. This question is a not part of an 
evaluation of suicide risk per se. Rather, it is one of the questions under the category “Recent Major 
Depressive Episode”. Study coordinator will call Dr. Hamidovic regarding any person reporting that 
he/she is suicidal (as part of Depression assessment). Dr Hamidovic will conduct an assessment by 
asking further questions related to suicidality using the attached MINI-International Neuropsychiatric 
Interview. Individuals scoring “low suicidality” and without imminent threat will be given referral to UIC 
Adult Psychiatry Service (312-996-2200) and contacted for follow-up after the screening. Dr. 
Hamidovic will contact Dr. Holden for an in-person assessment for individuals with moderate/high 
suicidality. For those exhibiting an immediate danger, authorities may be called if Dr Holden or Dr. 
Hamidovic view it necessary.   
 
Describe source documents and how data will be collected from source documents and incorporated 
into the database: During the screening session for both smokers and non-smokers, the research 

 
 
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team will have a hard copy of the screening flowsheet. The flowsheet will be used as a guidance 
document for researcher staff to conduct the series of screening procedures including obtaining 
informed consent, breath tests, questionnaires, specimen analysis, and health screens. Researchers 
will document on the flowsheet whether or not participants passed or failed each screening procedure 
and add any additional significant notes throughout the process. Similarly, the research team will also 
follow the flowsheet when running each of the two study sessions. For testing sessions, research 
data will be collected using software discussed above and all other study information will be entered 
into the REDCap database. All flowsheets will be stored in the PI’s UIC lab located on the first floor of 
the UIC College of Pharmacy.  
 
Describe the methods in which the data will be collected and stored (i.e., electronic, hard copy, 
specimens, artifacts, etc.): Please see Table 3.  
 
Describe where each method of data will be stored and how each method will be maintained in a 
secured manner (i.e., encryption, password protection, use of Qualtrics or REDCap, etc.): REDCap 
will only be accessed by the PI and her research team on password protected computers in the PI’s 
lab located on the first floor of UIC College of Pharmacy. This research project will be shared 
amongst the research team in REDCap and each member will be able to access the information by 
logging into the REDCap database under their individual profiles. Participants’ personal information 
will be stored in REDCap to ensure protection of personal identifiers. Software needed to collect 
study data from research devices during testing sessions will be downloaded on PI’s research laptop.  
As discussed, the PI’s laptop is password-protected and only available to members of the research 
team. No identifiers will be stored on the laptops. Hard copy files will be stored in locked cabinets 
inside the locked offices in the PI’s lab located in the UIC College of Pharmacy - 833 South Wood 
Street – Chicago, IL 60612. The PI’s lab consists of 3 rooms within UIC College of Pharmacy – room 
117A, 115, 112C. 
 
Describe who will have access to each method of data and how each method of data will be 
transferred to any collaborators: The Principal Investigator and her designated research team will 
have access to the research study information. There will be no collaborators involved in this study. 
Electronic data and hard copy files including research information will be stored and secured as noted 
above. 
 
11.0 Data and Safety Monitoring  
 
Addresses how problems/side effects will be identified and handled:  
Subjects will be asked to report any adverse events by specific questioning. The questions will 
specifically refer to symptoms of hypoglycemia and local irritation, but they will include additional 
questions about general adverse events as specified in the Consent Form. In addition, subjects will 
be asked to report any adverse events not listed on the Consent Form. The clinical course of each 
event will be followed until resolution, stabilization, or until it has been determined that the study 
treatment or participation is not the cause. If any serious events are detected, they will be followed up 
to determine the final outcome. Following completion of the study, participants will be instructed to 
report any adverse events and if the Principal Investigator determines that it is possibly related to the 
study treatment or participation, will be recorded and reported.   

 
 
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Subjects will be asked to report any adverse events they may have experienced related 
to the spray that was administered, the Nicorette nicotine gum, and the general study protocol. 
Information on all adverse events will be recorded immediately on the “Adverse Event Questionnaire” 
form provided by the PI’s lab. The “Adverse Event Questionnaire” lists all the expected AEs of 
intranasal insulin and nicotine gum as listed in the Nicorette information sheet and IND#120700 for 
intranasally administered Novolin R. In addition, blank space is included for study participants to list 
any additional AEs not listed on the form.  
Per policy of UIC OPRS, depending on the seriousness of the event, an adverse event will be 
reported either within 5 business days (in case of a serious event) or 15 business days (in an event 
the serious criteria is not met) as outlined in the UIC HSPP form “Prompt Reporting to the IRB”.  
Clinical course of each event will be followed until resolution, stabilization or until it has been 
determined that the study treatment or participation is not the cause. In addition to reporting adverse 
events related to spray administration, should they occur, the following non-drug related events be 
reported within 5 business days as well: 1) Breach of confidentiality, 2) Change to the protocol taken 
without prior IRB review to eliminate apparent immediate hazard to a research participant, 3) 
Complaint of a participant when the complaint indicates unexpected risks or the complaint cannot be 
resolved by the research team, or 4) Major protocol violations that are unplanned and unintentional, 
and 5) Apparent serious or continuing noncompliance. Anticipated and non-serious adverse events 
will be collected and entered into the study database for the purpose of comparing their incidence 
following intranasal insulin in comparison to the placebo spray administration. 
This form will be reviewed and signed first by the research team member, and also by the 
study PI. At that time, the PI will determine whether the reported events fall in the category of 
unanticipated AEs. Depending on the seriousness of the event, it will be reported either within 5 
business days (in case of a serious event) or 15 business days (in an event the serious criteria is not 
met) as outlined in the UIC HSPP form “Prompt Reporting to the IRB”.  Clinical course of each event 
will be followed until resolution, stabilization or until it has been determined that the study treatment or 
participation is not the cause. 
 
In addition to reporting adverse events related to spray administration or nicotine gum, 
should they occur, the following non-drug related events be reported within 5 business days as well: 
1) Breach of confidentiality, 2) Change to the protocol taken without prior IRB review to eliminate 
apparent immediate hazard to a research participant, 3) Complaint of a participant when the 
complaint indicates unexpected risks or the complaint cannot be resolved by the research team, or 4) 
Major protocol violations that are unplanned and unintentional, and 5) Apparent serious or continuing 
noncompliance. 
 
Anticipated and non-serious adverse events will be collected and entered into the study 
database for the purpose of comparing their incidence following intranasal insulin in comparison to 
the placebo spray administration. 
 
For studies that are minimal risk, describe how potential problems will be monitored and handled 
(e.g., breaches of confidentiality, emotional upset): This is not a minimal risk study.  
 
For research involving more than minimal risk to subjects, describe: Who will monitor adverse events 
(AEs) and unanticipated problems (UPs) involving risks to subjects or others and when events will be 
assessed: All research staff will be responsible for collecting AEs and UPs, but the ultimate 
responsibility and classification determination will rest with the PI. Whereas the study 

 
 
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coordinator/postdoc will sign the completed Adverse Event form, that form will be given to the PI who 
will use the “Adverse Event Tracking Form” for final classification of the AE. It will be documented on 
the form whether the event listed in the blank space on the Adverse Event form falls into 
anticipated/unanticipated and whether the nature of the event is serious/non-serious. In the event of 
unanticipated and/or serious event, the resolution of the AE will be tracked by the PI and all 
communications will be related to the Institutional Review Board.  
 
How AEs or UPs will be recorded and communicated amongst research team members and who is 
responsible for making the reports: At the end of each testing session, participants will be asked to 
complete “Adverse Event Questionnaire”. The research member facilitating the session and the PI will 
review and sign the form. The PI will record the determination of expectancy and seriousness of each 
event in the “Adverse Event Tracking Form”, and will communicate the result of this determination 
using UIC HSPP form “Prompt Reporting to the IRB”.   
 
The composition of the Data and Safety Monitoring Board (DSMB) and how frequently the DSMB 
meets, if one has been formed for the study: The Data and Safety Monitoring Board will be chaired 
by a physician – Dr. Mark R. Burge – and two additional members – Dr. James Nawarskas and Dr. 
Gretchen Ray – who are also clinicians. Dr. Burge is the Deputy Director of the Clinical and 
Translational Science Center at the University of New Mexico and a Regents’ and Distinguished 
Professor of Medicine. Dr. Nawarskas is an Associate Professor at the University of New Mexico’s 
College of Pharmacy. Dr. Gretchen Ray practices as a pharmacist clinician in the University of New 
Mexico Family Medicine clinics. The DSMB will meet every six months on a teleconference call. The 
type of safety information that will be assessed is the number and nature of adverse events that have 
been reported in the time since the previous call, results of olfactory function testing (i.e. Sniffin’ 
Sticks), POC glucose testing as well as the outcome of events discussed in previous meetings. The 
summary of the meetings and recommendations will be reported to the Principal Investigator as well 
as Human Research Protections Office within 15 days after the meeting. The board will meet on an 
interim basis (within 7 days) in a case of expedited cases in which the probability of treatment 
causality is high or a case of a change to the risks or potential benefits of the research (such as 
safety monitoring indicates that a particular side effect is more severe, or more frequent than initially 
expected). In such cases, the Principal Investigator will supply results of interim analysis including 
plans/safeguards to keep any data or DSMB analyses confidential.   
 
Identify how often AEs and UPs will be monitored and what events will be reported to the sponsor 
and/or the IRB: Adverse events and unanticipated problems will be monitored after each testing 
session as described above. Per policy of HSPP, expedited reporting of those events related to study 
participation that are unforeseen and indicate that participants or others are at an increased risk of 
harm, will occur within 5 working days from the time the investigator became aware of the event. This 
is the case for any adverse that occurs any time during or after research study, which in the opinion of 
the Principal Investigator is unexpected and related to the study procedures. The reporting process 
will consist of sending a written report to the IRB that includes a description of the event with 
information regarding the fulfillment of expedited reporting, follow-up/resolution and need for revision 
of the consent and/or other study documentation. Copies of each report and documentation of IRB 
notification and receipt will be kept in the Principal Investigator’s study file.  

 
 
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More rapid reporting requirements will be followed when deaths occur during the course of the 
research study. The event will be reported within 24 hours when the death is unforeseen 
(unexpected) and indicates participants (or others) are at an increased risk of harm. Report of the 
event within 72 hours will be filed for all other deaths, regardless of whether the death is related to 
study participation.  
 
Less serious events (1. Local adverse events or problems that are unanticipated and, while not 
meeting the criteria of serious, indicate research is associated with a greater risk of harm to 
participants or others than previously known, 2. External adverse events that are unanticipated, 
indicate research associated with a greater risk of harm to participants or others than previously 
known and more likely than not to have been caused by the procedures associated with or subject’s 
participation in the research 3. New information indicating an unexpected change to the risks or 
benefits of the research (i.e., an unanticipated problem), and 4. administrative hold by investigator, 
sponsor, regulatory authorities or other entities) will be reported within 15 business days. 
 
Describe stopping rules for the study: Stopping rules for the study will apply to expedited cases in 
which the probability of study treatment causality is high or a case of a change to the risks or potential 
benefits of the research (such as safety monitoring indicates that a particular side effect is more 
severe, or more frequent than initially expected). In the case of an expedited event, the study will be 
stopped until further information is gathered and a potential plan is formulated through consultation 
with the IRB. 
 
Describe what occurs if a subject withdraws prematurely: The PI and an appointed research team 
member will provide guidance to participants on the most appropriate method of discontinuation 
based on where they are in the study protocol. Recommendations will be given based on what 
procedures the subject has completed. For example, if the participant decides to withdraw 
participation immediately after receiving a spray, researchers will counsel the participant on common 
side effects they may experience. Researchers will provide a discharge summary of the session 
based on what the participant has completed. The team will provide supportive care to subjects as 
needed following all premature discontinuations.  
 
12.0 Statistical Considerations  
 
If a study incorporates qualitative rather than quantitative methods, indicate this and describe 
qualitative analysis and disregard the rest of this section: This study does not incorporate qualitative 
data analysis.  
 
Describe how the data will be examined and statistically analyzed to answer the objectives: Go/no-go 
accuracy will be evaluated in a 2 x 2 repeated measure ANOVA, with group, treatment and treatment 
x group interaction entered into the model.  
 
Provide a brief sample size calculation or description of sample size calculation.  Include methods 
and assumptions such as loss to follow-up, as appropriate: Effect size is estimated from Luijten et al 
(2011). In that study, effect size was 0.24. 
We anticipate 120 participants completing the study. An a priori power analysis was conducted 
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within and 2 between factors; a base correlation=0.6; power=0.95; alpha=0.05, the total of 120 
participants (60 per group) is required to capture an interaction between group and treatment on 
ERN.  
13.0 Regulatory Requirements  
 
13.1 Informed Consent  
 
Describe how informed consent will be obtained and who will obtain it: If a participant passes the 
initial REDCap survey, he/she will be contacted by a member of the research team to schedule an in-
person screening session. In-person screenings will take place in a private clinic room located in the 
Center for Clinical and Translational Science. Informed consent will be obtained at the beginning of 
the screening session. The “Screening Flowsheet” (submitted as part of this application) was 
developed by the PI including all the sections that need to be checked by the member of the research 
team obtaining the consent.  
 
Study participants will be given ample time to review the form. The consent procedure will be 
carried out in a private and quiet setting. Prior to initiating the procedure, the person consenting will 
ensure that the individual is adult, able to read and understands the English language. The most 
recent version of the consent form will be used. The individual obtaining the consent will summarize 
each section of the consent. Study participants will be told the following: “Take as much time as you 
need to read the entire consent form. Please inform me when you are done reading the form so I may 
answer any questions you have.” All the questions the subject had will be written on the coordinator 
flowsheet.  
 
The research team will retain the original consent form and store the document in a locked 
cabinet in a locked office within the PI’s lab. Only designated research team members appointed to 
this research study will be granted approval by the PI to obtain informed consent.  
 
Describe the training that will be completed by each member of the research team prior to being 
delegated to obtaining informed consent: Study personnel have completed the required CITI Training 
for Human Subject Protection. In addition to completion of the online training modules, study 
personnel will practice obtaining informed consent in the PI’s lab. The PI will provide feedback and 
expert tips to the research team for the consent form process. The PI has over 10 years of research 
experience and has lead numerous clinical research studies involving obtaining informed consent 
from human subjects.  The record of training of all research members will be kept on file in the 
laboratory.  
 
Describe where the informed consent document will be stored and who will have access to the 
informed consent documents: Informed consent documents will be stored as hard copy files in the 
PI’s lab located in the UIC College of Pharmacy. Only the PI and her designated research team for 
this study will have access to the informed consent. The research team is committed to being vigilant 
in the protection of patient information.  
 
If research involves minors, describe assent process, as applicable: The research study does not 
involve minors. This population will not be allowed to participate in the study. 
 

 
 
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If research involves non-English speaking subjects, describe the consenting process, as applicable: 
The research study does not involve non- English speaking subjects.  
 
Describe the use of any waivers, if applicable: Waivers will not be used for this research study. 
 
13.2 Subject Confidentiality 
 
Describe how the subject’s confidentiality will be maintained: Research personnel will take all feasible 
measures to ensure subject information remains secure and protected at all times. Paper files will be 
stored in a locked cabinet located in the PI’s UIC lab located in the College of Pharmacy located at 
833 South Wood Street, Chicago, IL 60612. Electronic files will be stored on a password protected 
computer that will only be accessible to the research team for this study.  REDCap, a widely used 
secure web application, will be the storage location for electronic files for this study. The details of the 
research project will be shared electronically in REDCap amongst the study team. Patient identifiers 
will be stored in REDCap, however, to ensure confidentiality subjects will be tracked by subject ID 
number throughout the study. Researchers will refer to subjects by their assigned ID number instead 
of using personal identifying information in research discussions. Unauthorized individuals who are 
not affiliated with the research study will not have access to sensitive subject information. 
 
Describe who will have access to the data: The PI and her appointed research team will have access 
to the study data.  Study generated data and sensitive participant information will only be accessible 
to researchers affiliated with this study. Study data will be stored on password-protected computers in 
the PI’s lab. Sensitive patient identifiers will be stored in REDCap on password protected computers 
only accessible to authorized individuals. 
 
Describe whether the data will be de-identified, coded, or retain identifiers: The REDCap database 
used for this research will include identifiable information in order for researchers to track participants 
for both research and safety purposes. Upon enrolling in the study, participants will be assigned a 
subject ID number. Throughout the study, participants will only be tracked by their subject ID number, 
not any personal identifiers. Hard copy files including screening documents for each participant, will 
only list the subject ID number. The exception to this are the forms which the subjects will have to 
sign (for example, the consent form and adverse event form). Those forms will be locked in a filing 
cabinet in a lab office which will also be locked.  
 
Describe plans for the destruction of any identifiers: Researchers will destroy participant identifiers 
after all analyses, publications, reports, and presentations are complete – i.e., 6 years following study 
completion. Identifiable information will not be used in these discussions. Following completion of the 
study, the research team will submit a final report to the UIC IRB as directed by the Office of the Vice 
Chancellor for Research. 
 
Provide justification for use of personally identifiable data or private health information (PHI): 
Researchers will not access any patient charts for this research study. As discussed, personal 
identifying information will be requested from participants at the beginning of the study for research 
and safety purposes. Researches will need documentation that participants meet study criteria (i.e. 
age between 18 – 40 years old) and will also need participant’s contact information for scheduling 

 
 
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testing session appointments. Participants will be asked detailed questions about their health to 
ensure it is safe to participate in the research. Throughout the study, participants will only be tracked 
by their subject ID number, not any personal identifiers. 
 
Describe whether a Certificate of Confidentiality will be required: A Certificate of Confidentiality will be 
required and obtained for this research study. Participants will be asked personal questions about 
their substance use history. Researchers are committed to protecting study participants’ 
confidentiality. The research team will inform participants about the purpose of the Certificate of 
Confidentiality prior to asking questions about substance use.  
 
13.3 Unanticipated Problems 
 
Describe process for reporting any unanticipated problems to IRB, sponsor (if applicable), and FDA (if 
an FDA-regulated study): Details of this process are outlined in Section 11.0. 
 
14.0 References 
actiCHamp manual. Manufacturer - BrainVision LLC.  
 
Benowitz NL, Gourlay SG. Cardiovascular Toxicity of Nicotine: Implications for Nicotine 
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