Clinical trial NCT03811951
Conditions: Smoking Cessation
Keywords: Tobacco Cigarettes Nicotine Insulin
Sponsor: University of Illinois at Chicago
Start date: 2018-09-12; Completion date: 2019-09-27
Enrollment: 4 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this study is to evaluate cognition in smokers and nonsmokers. It involves administration of intranasal insulin (Novolin R), an investigational medication followed by a brief non-invasive cognitive test. All participants will receive both Novolin R and placebo in two separate testing sessions.

Detailed description:
This program of research focuses on identifying neurologic biomarkers of smoking behavior in order to develop individualized smoking cessation aids. 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, the investigators will evaluate a biomarker using computerized tasks. Non-smokers and smokers will participate in two testing sessions where the biomarker will be critically evaluated after administration of intranasal insulin and compared to the cognitive processes elicited by placebo administration.

Arms: arm 1: All participants receive both Novolin R (experimental drug) and 14% NaCl (Sodium Chloride) solution (placebo), to be administered in randomly assigned order on two separate testing sessions. During administration of either Novolin R or 14% NaCl, participants will receive 1 spray in each nostril every 3 minutes for a total of 6 sprays. The nasal spray bottle delivers 0.1 ml of liquid per spray. Since the concentration of insulin in Novolin R is 100 IU/mL, six sprays will deliver a 60 IU dose. arm 2: All participants receive both Novolin R (experimental drug) and 14% NaCl solution (placebo), to be administered in randomly assigned order on two separate testing sessions. During administration of either Novolin R or 14% NaCl, participants will receive 1 spray in each nostril every 3 minutes for a total of 6 sprays. The nasal spray bottle delivers 0.1 ml of liquid per spray. Since the concentration of insulin in Novolin R is 100 IU/mL, six sprays will deliver a 60 IU dose.
Interventions: intervention 1: Novolin R
Intervention descriptions: intervention 1: 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 (potential Hydrogen) is adjusted to 7.4. Hydrochloric acid 2N (concentration) or sodium hydroxide 2N may be added to adjust pH. Novolin R vials are latex-free. The drug substance is being purchased from McKesson.

Protocol documents:
Prot_SAP_001.pdf: 
 
 
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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 
using G*power 3.1.9.2 for an ANOVA test, repeated measures and within-between interaction. With 2 


 
 
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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 
Replacement Therapy. J Am Coll Cardiol. 1997;29:1422-31. 
 
de la Monte SM. Intranasal insulin therapy for cognitive impairment and neurodegeneration: 
current state of the art. Expert Opinion on Drug Delivery. 2013;10:1699-1709. 
 
Fehm HL, Perras B, Smolnik R, Kern W, Born J. Manipulating neuropeptidergic pathways in 
humans: a novel approach to neuropharmacology? European Journal of Pharmacology. 
2000;405:43-54. 
 
Franken IH, van Strien JW, Kuijpers I. Evidence for a deficit in the salience attribution to errors in 
smokers. Drug Alcohol Depend. 2010;106:181–185. 
 
Hamidovic A, Khafaja M, Brandon V, Anderson J, Ray G, Allan AM, Burge MR. Reduction of 
smoking urges with intranasal insulin: a randomized, crossover, placebo-controlled clinical trial. 
Molecular Psychiatry. 2017;22:1413-1421. 
 
Kern W, Born J, Schreiber H, Fehm HL. Central nervous system effects of intranasally 
administered insulin during euglycemia in men. Diabetes. 1999:48:557-563.  
 
Luijten M, van Meel CS, Franken IH. Diminished error processing in smokers during smoking cue 
exposure. Pharmacol Biochem Behav. 2011b;97:514–520. 
 
Nedelcovych MT, Gadiano AJ, Wu Y, Manning AA, Thomas AG, Khuder SS, Yoo SW, Xu J, 
McArthur JC, Haughney NJ, Volsky DJ, Rais R, Slusher BS. Pharmacokinetics of Intranasal 
versus Subcutaneous Insulin in the Mouse. 2018. ACS Chem Neurosci.  
 


 
 
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Nicorette Informational Pamphlet. GSK Group. 2017. 
 
Ott V, Benedict C, Schultes B, Born J, Hallschmid M. Intranasal administration of insulin to the 
brain impacts cognitive function and peripheral metabolism. Diabetes Obesity & Metabolism. 
2012;14:214-221. 
 
Rass O, Fridberg DJ, O'Donnell BF. Neural correlates of performance monitoring in daily and 
intermittent smokers. Clinical Neurophysiology. 2014;125:1417-1426. 
 
Reger MA, Craft S. Intranasal insulin administration: A method for dissociating central and 
peripheral effects of insulin. Drugs of Today. 2006;42:729-739. 
 
Schmid V, Kullmann S, Gfrorer W, Hallschmid M, Lipp HP, Haring HU, Preissl H, Fritsche A, Heni 
M. Safety of intranasal human insulin: A review. Diabetes Obes Metab. 2018. 
 
Shemesh E, Rudich A, Harman-Boehm I, Cukierman-Yaffe T. Effect of Intranasal Insulin on 
Cognitive Function: A Systematic Review. Journal of Clinical Endocrinology & Metabolism. 
2012;97:366-376. 
 
Strachan MWJ. Insulin and cognitive function in humans: experimental data and therapeutic 
considerations. Biochemical Society Transactions. 2005;33:1037-1040. 
 
West R, Hajek P, Foulds J, Nilsson F, May S, Meadows A. A comparison of the abuse liability and 
dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology. 
2000;149:198-202. 
 

ICF_000.pdf: 
Informed Consent 
                           Version 7 10/29/2018 
Page 1 of 10 
 
 
 
 
 
 
 
 
 
University of Illinois at Chicago 
Research Information and Consent for Participation in Biomedical Research 
“Neurologic Biomarkers of Smoking Behavior” 
 
You are being asked to participate in a research study. The study team is required to provide a 
consent form such as this one to tell you about the research, to explain that taking part is 
voluntary, to describe the risks and benefits of participation, and to help you to make an 
informed decision. Feel free to ask a member of the study team any questions you may have. 
 
Principal Investigator Name and Title: Dr. Ajna Hamidovic, PharmD, MS – Assistant 
Professor 
Department and Institution: UIC College of Pharmacy – Department of Pharmacy Practice 
Address and Contact Information: 833 South Wood Street – Chicago, IL 60612  
Phone: 312-996-8838 Email: cedar@uic.edu 
Emergency Contact Name and Information: Dr. Ajna Hamidovic, PharmD, MS  
Phone: 312-355-1713 Email: ahamidov@uic.edu 
Sponsor: University of Illinois at Chicago 
 
Why am I being asked? 
 
 
 
 
 
You are being asked to be a subject in a research study about the effects of intranasal insulin on 
brain activity. 
 
You have been asked to participate in the research because you have been identified as either a 
cigarette smoker or non-smoker between the ages of 21-40 years old. 
 
Your participation in this research is voluntary.  Your decision whether or not to participate will 
not affect your current or future dealings with the University of Illinois at Chicago.  If you 
decide to participate, you are free to withdraw at any time without affecting that 
relationship.  
 
Approximately 120 subjects may be involved in this research at UIC.  
 
What is the purpose of this research? 
 
 
 
 
This research is being done to better understand the effect of intranasal insulin on brain activity 
in smokers and non-smokers. Understanding this outcome may lead to drug development that is 
not only patient-specific, but possibly more effective than currently available smoking cessation 
aids. Although there are several FDA-approved treatments on the market, only approximately 
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6% of an estimated 40 million smokers successfully quit. Taking a more individualized approach 
to resolving this healthcare concern may lead to higher quit rates amongst smokers.   
 
The insulin treatment used in this study is not FDA approved and is therefore investigational. 
 
What procedures are involved? 
 
 
 
 
This research will be performed at the UIC Center for Clinical and Translational Science (CCTS) 
located on 914 South Wood Street Chicago, IL 60612. Participants will complete screening and 
testing in a private clinic room in CCTS.  
 
Before participating in the study, you will be asked to complete several screening tests to 
determine if you are eligible for the study. The screening session (i.e. today) will take 
approximately 3 hours. The screening tests will include the following: 
 
1. Urine drug and pregnancy screens – All subjects will be required to have a negative 
drug screen during screening (i.e. today) and subsequent testing sessions to continue 
participation in the study. In addition to urine drug screens, female participants will also 
be asked to complete a urine pregnancy test. Female participants will be required to have 
a negative pregnancy test during screening (i.e. today) and subsequent testing sessions 
to continue participation in the study.  
2. Shipley IQ Test – The Shipley IQ Test is a brief measure of cognitive functioning. The 
test will include a 40 question vocabulary test on word meaning. You will be asked to 
complete the test in 10 minutes. 
3. Breath Alcohol Test – The breath alcohol test will measure your breath alcohol level to 
rule out recent alcohol intake. Drinking alcohol up to 48 hours before your 
appointment (either screening or testing session) is not permissible for the purpose 
of this study. You will be asked to take a deep breath and blow into the mouthpiece of 
the breath alcohol device to test your levels.  
4. Point-of-care glucose check – You will be asked to provide a blood sample. A nurse will 
take a drop of blood from your finger and measure your plasma glucose levels to ensure 
that your blood glucose levels are within the normal range. 
5. Carbon Monoxide Monitor – The purpose of measuring the CO level is to classify you as 
either a smoker or a non-smoker.  
6. Baseline Demographics - You will be asked basic demographic questions in a survey.  
7. Fagerstrom Test for Nicotine Dependence (FTND) – If you are a cigarette smoker, you 
will be asked questions about your level of nicotine dependence. 
8. Substance Use History – You will be asked detailed questions about your substance use 
history in this survey.  This survey will ask you very personal questions about your drug 
use history. This study has a Certificate of Confidentiality issued by the government to 
protect the privacy of participants involved in this research. The Certificate of 
Confidentiality allows the research team to refuse to disclose identifying information 
about you in any civil, criminal, administrative, legislative, or other proceeding, whether 
at the federal, state, or local level. 
9. Structured Clinical Interview – You will be asked detailed questions about your mental 
health. This interview will take approximately 30 minutes. 


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10. Hair – You will be asked if you have thick, braided hair. If your hair is in tight braids, it 
may be difficult for the study coordinator to establish a clear signal from your scalp to the 
EEG cap with gel. You will have to unbraid your hair prior to the beginning of the study. 
If you are unsure of whether your hair needs to be unbraided for the experiment, please 
contact the CEDAR Lab.   
 
If you are eligible to participate in the study after completing the in-person screening procedures, 
you will be asked to schedule appointments for 2 testing sessions. You will need to come to the 
study site on 2 separate days separated by approximately 1 week. 
 
You will need to abstain from any illicit drug intake during the course of this study. 
Drinking alcohol 48 hours prior to each study session is not permissible for the purpose of 
this study. Each of those visits will take 4 hours. If you are a smoker, you will be allowed to 
resume smoking at the end of the 4-hour session.  
 
If you are a smoker, you may smoke the normal amount of cigarettes that you usually smoke 
within the first 30 minutes of waking prior to each session. After the first 30 minutes, you must 
refrain from smoking for the rest of the morning. It is important that you smoke the same amount 
of cigarettes prior to both sessions. For example, if you usually smoke 2 cigarettes upon waking, 
you should smoke 2 cigarettes prior to the first session and 2 cigarettes prior to the second 
session.  
 
The study procedures for each visit is as follows. 
 
1. The study session will begin at 8a.m. You will be asked to provide a urine drug sample, 
alcohol breath sample, and carbon monoxide breath sample at the beginning of each 
testing session.  
2. At 8:30a.m., you will be instructed to take a chewing gum break. If you are a smoker, a 
member of the research team will provide a strip of Nicorette® nicotine gum. As per the 
instructions given by Nicorette, you will chew the gum slowly until you experience a 
tingling sensation, then place the gum between your cheek and gum until the tingle 
subsides. You will repeat this procedure until most of the tingle is undetectable (20-30 
minutes). If you are a non-smoker, you will be given a piece of generic (non-nicotine) 
gum and can chew at your own pace. 
3. At 8:50a.m., a study nurse will take a blood sample from your arm to establish your 
baseline blood nicotine level. The nurse will place a needle in a vein in your arm, and a 
4mL blood sample will be taken from it to determine your baseline nicotine blood levels. 
This step is important to ensure that nicotine levels can be compared between testing 
sessions. 
4. At 9:00a.m., a study nurse will conduct a POC blood glucose check by taking a drop of 
blood from your finger to examine your blood glucose level.  
5. At 9:05a.m., a study nurse will conduct a physical examination of the nares (nostrils). 
This examination will be conducted to ensure that the condition of your nares is suitable 
for intranasal administration of insulin. 
6. From 9:15 to 10:00a.m., you will be allowed to relax. We will supply magazines and 
books for you to choose from. 


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7. The nasal spray administration will start at 10:00a.m. You will either receive insulin or 
placebo nasal spray. You will not know which treatment you have received. You will 
spray once in each nostril every 3 minutes for a total of 6 sprays (2 sprays at 10:00a.m., 2 
sprays at 10:03a.m., and 2 sprays at 10:06a.m.). During treatment, you will be given a 
questionnaire to rate spray effects. If you receive insulin in the first session, you will 
receive placebo in the second session, and vice versa. 
8. At 10:10a.m., a member of the research team will set up the electroencephalography 
(EEG) equipment. The EEG is a non-invasive device which will track and record your 
brain wave patterns during several tasks in the testing session. EEG equipment includes a 
cap that you will wear on your head, an EEG device that will record your brain activity, 
and 32 cords connecting the cap to the EEG. The equipment will also be connected to a 
laptop for the study team to analyze your brain waves in real-time. The EEG setup will be 
completed by 10:30a.m. 
• You will be asked to brush your hair to ensure accurate EEG data collection.  
• The study coordinator will put the EEG cap on your head. The EEG cap is non-
invasive and will be placed on your head similar to a hat.  
• Next, the study coordinator will put electrolyte gel in each of the 32 electrode 
slots on the EEG cap. This process involves using a syringe with a blunt needle to 
insert gel between each electrode and your scalp. In order to ensure a clear signal, 
the study coordinator will move some of your hair with the blunt needle using a 
gentle scratching motion. The gel will likely get in your hair during this step but 
can be washed out with water and shampoo after the study session is complete.  
9. At 10:30a.m., you will complete a task on a computer while study coordinators observe 
your brain activity through the EEG recording. You will be instructed to respond as 
quickly and accurately as possible. In the task, you will be given instructions on what 
specific keyboard buttons to press in response to seeing specific letters and shapes on the 
screen.  
10. At 11:40a.m., the study coordinator will wrap up the testing session. At the end of the 
session, you will be asked to complete a form asking if you experienced any side effects 
or discomfort from your participation in the session. In addition, you will be given the 
instructions for the next study session, or for the completion of the study, depending on 
whether the end of the session occurs after the first or the second session. A member of 
the study team  will answer any questions you may have or address any concerns related 
to the study procedure.  
11. At 11:40a.m., a study nurse will conduct a POC blood glucose check by taking a drop of 
blood from your finger to examine your blood glucose level. 
• The possibility of experiencing low glucose (i.e. hypoglycemia) is very low. 
However, if your blood glucose levels are below the euglycemic level (<70 
mg/dL) you will be treated for hypoglycemia.  
• You will be given 15 grams of glucose (4 oz of orange juice) and your glucose 
level will be rechecked in 15 minutes. The process will be repeated if you are still 
hypoglycemic.  
• Once treated, you will be given a snack (a granola bar) to eat in order to prevent 
recurrence. You will then engage in a light activity such as reading for an hour.  
• Following this hour, you will drink 4 ounces of orange juice and eat a granola bar.  


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• At this time, we will retest your blood glucose levels. Upon confirmation that you 
are still euglycemic, you will be discharged and compensated for your time spent 
in the session. 
12. If you are not treated for hypoglycemia (i.e. are euglycemic), the testing session will end 
at 12:00p.m. If you are treated for hypoglycemia, the testing session will end at 1:00p.m. 
 
What are the potential risks and discomforts? 
 
You may have side effects while in the study. Everyone taking part in the study will be followed 
carefully for any side effects. The study drug, intranasal insulin, has been tested in the healthy 
population and Alzheimer’s disease patients in about 2,000 patients. There have been no serious 
side effects reported resulting from the treatment. However, this medication has not been tested 
in solely nicotine dependent individuals, so doctors do not know all the side effects that may 
happen. The potential toxicity of intranasal insulin in the nasal cavity and other exposed tissues 
has not been tested in animal studies. 
 
You should report to the investigator any side effects you experience while taking part in the 
study. There is a potential of developing the following side effects: 
• Nasal irritation/runny nose (42%) 
• Confusion/inability to complete routine tasks (16%) 
• Sweating (11%) 
• Nonspecific pain (11%) 
• Shaking (11%) 
• Anxiety (11%) 
• Watering eyes (11%) 
• Dizziness (5%) 
• Headache (5%) 
• Visual disturbances, such as double or blind vision (5%) 
• Tingling sensation around the mouth (5%) 
• Diarrhea (5%) 
• Restlessness (5%) 
• Discomfort (5%) 
• Menorrhagia/abnormal bleeding at menstruation (5%) 
• Anosmia/loss of smell 
• Insomnia/trouble sleeping 
 
If you experience any of these symptoms, you should contact the investigator immediately. 
 
Anosmia (loss of smell) may be experienced when zinc (an ingredient in insulin solution) is 
administered nasally. The concentration of zinc that was found to be toxic is between 0.01% and 
0.05%. The concentration of zinc in our study is 0.0007%. Though this is a low concentration, it 
is not known how likely it is that permanent loss of smell will occur. Insomnia may occur the 
night following the session, with a stabilization and return to normal sleeping pattern the 
following night. 
 


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Hypoglycemia (low blood sugar) may be experienced with insulin administration. However, the 
amount of intranasal insulin you will receive (60 IU) is unlikely to cause hypoglycemia, as 
occurrences of hypoglycemia have not been reported in studies with similar doses. For more 
information about risks and side effects, ask the investigator. 
 
Other likely risks and discomforts in this study include: 
• Possible side effects of blood drawing include discomfort, bruising and/or bleeding at the 
needle site (>20%); dizziness and infection (<2%). 
• The process for putting the EEG head cap on your head. In order to collect accurate data, 
the research will have to insert gel into each of the 32 electrode slots of the EEG head cap 
using a plastic syringe. The study team will need to make sure the gel makes contact with 
your scalp for quality EEG signal readings. This process will require researchers to 
scratch your scalp using the plastic gel-filled syringe, which may cause discomfort. The 
research team will make every effort to be as gentle as possible throughout this process. 
The EEG cap is non-invasive and will be placed on your head similar to a hat. 
• The process of putting gel in the EEG head cap. After putting the electrolyte gel into each 
of the 32 slots of the EEG head cap, you will have gel in your hair. Your hair will be 
sticky due to the substance of the gel, which may cause discomfort. 
• Risk of potential loss of confidentiality. Information that identifies subjects will be used 
in this study and shared with research staff. However, the research team will make every 
effort to protect subject’s private health information and guard against any loss of 
privacy.  
• Risk of stress, anxiety, or both. Some of the questions asked may cause you to have stress 
or anxiety. If so, contact the University of Illinois Health system at (312) 996-2200 to 
request information from UI Health Psychiatric Services. 
 
What are the reproductive risks?   
 
If you are a woman: Participating in this research may involve risks to pregnant women and/ or 
an unborn baby which are currently unforeseeable.  To protect against possible side effects of the 
study drug, if you are pregnant or nursing a child you may not take part in this study. As part of 
this study, we will be performing urine pregnancy testing. If you become pregnant, your 
participation will be stopped. 
 
Will I be told about new information that may affect my decision to participate?  
 
During the course of the study, you will be informed of any significant new research findings 
(either good or bad), such as changes in the risks or benefits resulting from participation in the 
research or new alternatives to participation, that might cause you to change your mind about 
continuing in the study.  If new information is provided to you, your consent to continue 
participating in this study may be re-obtained. 
 
Are there benefits to taking part in the research?  
 
 
It is hoped that knowledge gained from this research may benefit others who are trying to quit 
smoking in the future. You will not directly benefit from your participation in this research. 


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What other options are there? 
 
You have the option to not participate in this study.  
 
What about privacy and confidentiality? 
 
The people who will know that you are a research subject are members of the research team, and 
if appropriate, your physicians and nurses.  No information about you, or provided by you, 
during the research, will be disclosed to others without your written permission, except if 
necessary to protect your rights or welfare (for example, if you are injured and need emergency 
care or when the UIC Office for the Protection of Research Subjects monitors the research or 
consent process).  
 
Study information which identifies you and the consent form signed by you will be looked at 
and/or copied for examining the research by:  
• Food and Drug Administration (FDA)  
• Funding Agency 
• UIC Office for the Protection of Research Subjects, State of Illinois Auditors 
 
A possible risk of the research is that your participation in the research or information about you 
and your health might become known to individuals outside the research. 
 
Paper documents will be stored in a locked filing cabinet in the Principle Investigator’s lab 
located in the UIC College of Pharmacy in rooms 117A, 112C, and 115. Access to electronic 
research data will be limited to Ajna Hamidovic and her designated study team and will be stored 
in a secure database on password-protected computers.  
 
The research team will be responsible for maintaining files and storing data for all subjects of the 
study.  Researchers will write about the combined data that is gathered from the study. Any talks 
or papers about this study will not identify the subject. Researchers will make every effort to 
keep the information collected for this study confidential.   
 
Research personnel will assign participants with a personal identification number (PIN).  For the 
duration of the study, patients will be tracked based on their PIN, not by any personal 
information.  Personal information from participants will be accessed on secure, password- 
protected electronic databases.  
 
When the results of the research are published or discussed in conferences, no information will 
be included that would reveal your identity.   
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. law.  This web site will not include information that can identify you.  At most, the Web 
site will include a summary of the results.  You can search this Web site at any time. 
  


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To help us protect you and the information we will be collecting from you, this research has been 
given a Certificate of Confidentiality by the U.S. government.  This Certificate means that 
researchers cannot be forced, even by courts or the police, to disclose any information about you. 
 
The Certificate does not stop you from disclosing, or agreeing in writing to allow researchers to 
disclose, information about you.  For example, if you would like an employer or insurer to know 
something about you that is documented in this research, you can write and sign a statement 
telling the researchers it is okay to give your employer or insurance company information. 
 
 
What if I am injured as a result of my participation?  
 
If you get ill or injured from being in the study, UIC will help you get medical treatment. You 
should let the study doctor know right away that you are ill or injured. If you believe you have 
become ill or injured from this study, you should contact Dr. Hamidovic at telephone number 
312-996-8838.  
 
You should let any health care provider who treats you know that you are in a research study. If 
you do seek medical treatment, please take a copy of this document with you because it may help 
the doctors where you seek treatment to treat you. It will also provide the doctors where you seek 
treatment with information they may need if they want to contact the research doctors. 
 
You or your health insurance plan will be billed. No money has been set aside to pay the costs of 
this treatment. Health insurance plans may or may not cover costs of research-related injury or 
illness. You should check with your insurance company before deciding to participate in this 
research study. Costs not covered by insurance could be substantial.  
 
UIC has not set aside any money to pay you or to pay for your treatment if you get ill or injured 
from being in the study. There are no plans for the University to provide other forms of 
compensation (such as lost wages or pain and suffering) to you for research related illnesses or 
injuries. The only exception to this policy is if it is proven that your injury or illness is directly 
caused by the negligence of an UIC employee.  
 
By signing this form, you are not giving up any legal rights to seek compensation of injury.  
 
What are the costs for participating in this research?    
 
There are no costs to you for participating in this research.  
 
Will I be reimbursed for any of my expenses or paid for my participation in this research? 
 
You will receive a cash payment of $100 for completing each study visit. You will receive a total 
cash payment of $200 for completing both study visits.  
 
You will receive your payment at the end of the study in cash.  
 


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Can I withdraw or be removed from the study?  
 
If you decide to participate, you are free to withdraw your consent and discontinue participation 
at any time without affecting your future care at UIC. 
 
You have the right to leave a study at any time without penalty.  
 
The study team also has the right to stop your participation in this study without your consent if: 
• They believe it is in your best interests; 
• You were to object to any future changes that may be made in the study plan; 
• The sponsor of the research has decided to stop the research,  
• If you do not follow the study procedures  
• If new information is identified 
 
Who should I contact if I have questions?  
 
Contact Dr. Hamidovic and her research team at 312-996-8838 or cedar@uic.edu 
• if you have any questions about this study or your part in it,   
• if you feel you have had a research-related injury (or a bad reaction to the study 
treatment), and/or 
• if you have questions, concerns or complaints about the research..  
 
What are my rights as a research subject? 
  
If you have questions about your rights as a research subject or concerns, complaints, or to offer 
input you may call the Office for the Protection of Research Subjects (OPRS) at 312-996-1711 
or 1-866-789-6215 (toll-free) or e-mail OPRS at uicirb@uic.edu. 
 
What if I am a UIC student? 
 
 
 
You may choose not to participate or to stop your participation in this research at any time.  This 
will not affect your class standing or grades at UIC.  The investigator may also end your 
participation in the research.  If this happens, your class standing or grades will not be affected.  
You will not be offered or receive any special consideration if you participate in this research. 
 
What if I am a UIC employee?   
 
 
Your participation in this research is in no way a part of your university duties, and your refusal 
to participate will not in any way affect your employment with the university, or the benefits, 
privileges, or opportunities associated with your employment at UIC.  You will not be offered or 
receive any special consideration if you participate in this research 
 
Remember:   
 
 
 
 


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Your participation in this research is voluntary.  Your decision whether or not to participate will 
not affect your current or future relations with the University.  If you decide to participate, you 
are free to withdraw at any time without affecting that relationship. 
 
Signature of Subject  
 
 
I have read (or someone has read to me) the above information.  I have been given an 
opportunity to ask questions and my questions have been answered to my satisfaction.  I agree to 
participate in this research.  I will be given a copy of this signed and dated form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
Printed Name 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Person Obtaining Consent 
 
 
Date (must be same as subject’s) 
 
 
 
 
 
 
 
 
Printed Name of Person Obtaining Consent