Clinical trial NCT03575403
Conditions: Alcohol Use Disorder
Sponsor: Craig Rush
Start date: 2018-09-01; Completion date: 2023-03-15
Enrollment: 19 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
This study will evaluate the behavioral effects of alcohol during maintenance on placebo, duloxetine, methylphenidate and duloxetine combined with methylphenidate using sophisticated human laboratory methods.

Detailed description:
Prior to the outbreak of the COVID-19 virus and subsequent work-from-home orders from the state of Kentucky government, participants completed five overnight sessions at theUniversity of Kentucky Inpatient Research Unit in the medical center. The protocol was then changed to have five sessions scheduled to be completed on an outpatient basis in the late afternoon/early evening. This protocol change was enacted following the resumption of research in the fall of 2020.

For both the inpatient and outpatient portions of this protocol, the first of these sessions was a practice session to familiarize participants with experimental procedures. The subsequent four experimental sessions were conducted following one-week maintenance on a methylphenidate dose (0, 20, 40, and 60 mg/day; within-subjects factor) over the span of four weeks. Participants were assigned to either an active duloxetine arm (60 mg/day) or placebo arm (between-subjects factor) also for the span of four weeks. The outcome measures collected were the same for both the inpatient and outpatient aspects of the study.

Subjects received 30 mg of oral duloxetine one time daily. Note: only 2 subjects were enrolled in this arm prior to the arm being removed in the summer of 2020. Data from this arm will not be reported in order to avoid any HIPAA violation due to the small number of subjects in this arm.

Please note that at the initial execution of the study, there were three duloxetine arms: 0, 30, and 60 mg/day. Two participants received 30 mg/day. However, visual inspection of their data revealed that their data was not appreciably different from participants in the 60 mg/day duloxetine arm. Therefore, we have added the data from these two participants to the 60 mg/day duloxetine arm for all reported data.

Arms: arm 1: Subjects received oral placebo capsules one time daily. arm 2: Subjects received 60 mg of oral duloxetine one time daily. arm 3: Subjects received 30 mg of oral duloxetine one time daily. Note: only 2 subjects were enrolled in this arm prior to the arm being removed in the summer of 2020. Data from this arm will not be reported in order to avoid any HIPAA violation due to the small number of subjects in this arm.
Interventions: intervention 1: Alcohol intervention 2: Placebos intervention 3: Duloxetine (60 MG) intervention 4: Methylphenidate intervention 5: Duloxetine (30 MG)
Intervention descriptions: intervention 1: In each arm and during sessions, subjects will receive doses of alcohol designed to raise breath alcohol levels (BAL) to 0.03 g/dl. intervention 2: Subjects will receive oral placebo capsules. intervention 3: Subjects will receive 60-mg of oral duloxetine capsules. intervention 4: Subjects will receive methylphenidate capsules. intervention 5: Subjects will receive 30-mg of oral duloxetine capsules.

Protocol documents:
Prot_SAP_001.pdf: 
Document Coversheet 
 Study Title: A Novel Drug Combination for Alcohol-Use Disorders: A Human Laboratory Study 
Institution/Site: 
University of Kentucky 
Document (Approval/Update) Date: 
ICF: 2/15/23; Protocol 5/31/18 
NCT Number: 
NCT03575403 
IRB Number 
44796 
Coversheet created: 
2/26/24 


 TO:
Craig Rush, 
Behavioral Science
PI phone #: 8593236130
PI email: crush2@uky.edu
 
 FROM:
Chairperson/Vice Chairperson
Medical Institutional Review Board (IRB)
 SUBJECT:
Approval of Protocol
 DATE:
5/31/2018
 
Initial Review
 Approval Ends:
 IRB Number:
 5/23/2019
 44796
 
 
 
                               
                
                               
              
                   
The Medical Institutional Review Board approved minor revisions requested at the convened meeting on 5/24/2018 for your protocol entitled:  
Behavioral Effects of Drugs: Inpatient (36) (Alcohol, Duloxetine, and Methylphenidate)               
Approval is effective from 5/24/2018 until 5/23/2019 and extends to any consent/assent form, cover letter, and/or phone script.  If applicable, the IRB approved
consent/assent document(s) to be used when enrolling subjects can be found in the "All Attachments" menu item of your E-IRB application.  [Note, subjects can only be
enrolled using consent/assent forms which have a valid "IRB Approval" stamp unless special waiver has been obtained from the IRB.]  Prior to the end of this period, you
will be sent a Continuation Review Report Form which must be completed and submitted to the Office of Research Integrity so that the protocol can be reviewed and
approved for the next period.   
In implementing the research activities, you are responsible for complying with IRB decisions, conditions and requirements.  The research procedures should be
implemented as approved in the IRB protocol.  It is the principal investigator's responsibility to ensure any changes planned for the research are submitted for review and
approval by the IRB prior to implementation.  Protocol changes made without prior IRB approval to eliminate apparent hazards to the subject(s) should be reported in
writing immediately to the IRB.  Furthermore, discontinuing a study or completion of a study is considered a change in the protocol’s status and therefore the IRB should
be promptly notified in writing.
For information describing investigator responsibilities after obtaining IRB approval, download and read the document "PI Guidance to Responsibilities, Qualifications,
Records and Documentation of Human Subjects Research" available in the online Office of Research Integrity's IRB Survival Handbook. Additional information
regarding IRB review, federal regulations, and institutional policies may be found through ORI's web site. If you have questions, need additional information, or would like
a paper copy of the above mentioned document, contact the Office of Research Integrity at 859-257-9428.
  
Section 1 Page 1 of 1


 
RESEARCH PROCEDURES 
Participants that meet the inclusion criteria will participate as outpatients at the Laboratory of 
Human Behavioral Pharmacology (LHBP) of the University of Kentucky. 
Thirty-two (≈11 women) non-treatment-seeking individuals with alcohol (ALC) use disorder 
(AUD) will complete the study. Participants, recruited from the community, will earn $40/session 
and a $40/session completion bonus if they finish the protocol. To maximize medication 
adherence, a contingency management approach will be used wherein participants will receive a 
monetary bonus each day that medications are administered per protocol as verified by Wisepill®. 
Payments will start at $5 and increase by $2 each consecutive day of dosing adherence. 
The study protocol will use previously developed methods that have predictive validity for AUD 
treatment efficacy (Drobes et al., 2003; Hendershot et al., 2016; O’Malley et al., 2002). More 
specifically, the sensitivity of this clinical laboratory approach was established with a medication 
already known to be effective for AUD (i.e., naltrexone). After screening, participants will complete 
the protocol as outlined in Table 1. After completing the protocol, all participants will be offered 
referral to a treatment program per the NIAAA National Advisory Council guidelines (National 
Council on Alcohol, 1988; Sinha et al., 1999). 
 
Day 
Table 1: Experimental Procedures 
0 
Practice Session. ALC consumption designed to bring BAL to 0.03 g/dl. Subjective, physiological, 
and cognitive-behavioral measures collected (described in Table 2). Participants randomly 
assigned to a duloxetine (DUL) condition prior to completing this session. 
1-6 
DUL (0 or 60 mg/day) and methylphenidate (MTH; 0 mg/day) administered once daily (at 0900h) 
for 6 days. 
7 
Experimental Session. ALC consumption designed to bring BAL to 0.03 g/dl. Subjective, 
physiological, and cognitive-behavioral measures collected (described in Table 2). DUL-MTH 
maintenance continues. 
8-13 
DUL (0 or 60 mg/day) and MTH (20 mg/day) administered once daily (at 0900h) for 6 days. 
14 
Experimental Session. Details are the same as during Day 7. DUL-MTH maintenance continues. 
15-20 
DUL (0 or 60 mg/day) and MTH (40 mg/day) administered once daily (at 0900h) for 6 days. 
21 
Experimental Session. Details are the same as during Day 7. DUL-MTH maintenance continues. 
22-27 
DUL (0 or 60 mg/day) and MTH (60 mg/day) administered once daily (at 0900h) for 6 days. 
28 
Experimental Session. Details are the same as during Day 7. Participant receives taper 
medications to begin on the morning of Day 29.  
29 
Medical screening repeated. Follow-up visits scheduled. 
 
Participants will be instructed to maintain their standard diet, ALC and cigarette intake 
throughout participation, with the exception that they will be asked to abstain from ALC for at least 
12h prior to a session. All participants will provide urine and expired-breath samples prior to 
experimental sessions. The presence of drugs of abuse in the urine or positive BALs upon arrival 
for experimental sessions will result in rescheduling of the session. Repeated occurrences will 
result in study dismissal. Participants will not be allowed to smoke tobacco cigarettes during 


experimental sessions, consistent with previous work (O’Malley et al., 2002). 
Practice Session. This session will familiarize participants with the experimental procedures 
described below, prior to maintenance dosing, and to demonstrate equivalency between the DUL 
cohorts on their baseline and physiological responses to ALC.  
Randomization to a DUL Cohort and Medication Maintenance. After screening and prior to 
completing the practice session, a participant will be randomized to a DUL dose condition with an 
urn randomization procedure to ensure balance across the DUL conditions along two variables: 
1) severity of AUD (i.e., mild, moderate) and 2) sex (M/F). 
Delayed-Release Capsules of DUL (0 or 60 mg/day) (Cymbalta®) and long-acting MTH (0, 
20, 40, 60 mg/day) (Metadate CD®) will be prepared by over-encapsulating commercially 
available doses in a size 0 capsule. Capsules are then filled with lactose monohydrate powder, 
N.F. Placebo capsules will be identical, but contain only lactose. The dosing regimen of DUL and 
MTH were selected based upon clinical recommendations. DUL and MTH will be administered 
concurrently once daily (0900h). 
Both DUL and MTH will be administered once a day using delayed-release (DUL) or long-
acting (MTH) formulations. DUL produces peak blood levels approximately 6 h after dosing, but 
DUL levels in plasma remain relatively stable for at least 24 h after dosing. Participants 
randomized to 60 mg/day DUL will initially receive 30 mg/day for 2 days and the target dose (i.e., 
60 mg/day) for 4 more days prior to completing the experimental session. This dosing regimen 
will allow participants to acclimate to a lower DUL dose before receiving the target dose. The long-
acting formulation of MTH produces a biphasic profile with effects peaking 2 and 6 h after dosing. 
Levels of MTH decrease after the 6 h peak but are detectable for at least 24 h after dosing. This 
stable decrease for MTH, especially if given in the morning, will reduce any sleep disruptions 
associated with long-acting MTH administration while also ensuring clinically effective blood levels 
of MTH during participant waking hours. The MTH doses will be tested in ascending order 
because clinical guidelines recommend increases of 20 mg at weekly intervals to a maximum 
dose of 60 mg/day. 
The duration of maintenance needed to reach steady-state plasma concentrations was 
calculated based on the pharmacokinetic profiles of delayed-release DUL and long-acting MTH, 
both of which follow first order kinetics. According to first-order kinetics, 4-7 half-lives is needed 
to attain steady state. The half-life of delayed-release DUL and long-acting MTH is approximately 
12 and 5 hours, respectively. The maintenance period (i.e., 3-6 days) on each dose of DUL and 
MTH is sufficient to achieve steady state prior to completing experimental session in which an 
ALC challenge is administered. Participants will be provided with additional maintenance 
medications in the event that they are unable to attend an experimental session due to unforeseen 
circumstances. Overall, the use of the proposed formulations of DUL and MTH will result in more 
stable concentrations of clinically effective doses. 
Medication adherence will be assessed using two approaches. First, all study medications will 
be encapsulated with 100 mg riboflavin to assess adherence via fluorescence detection. Second, 
participants will administer study capsules using the Wisepill® digital monitoring system. This 
system uses mobile phone and Internet technologies to provide real-time medication 
management. When a participant takes a capsule at the scheduled time, an electronic medication 
event record is sent to the Wisepill® central management system. Failure to take the capsule at 
the scheduled time results in a reminder “text” message being sent to the participant and the 
researchers. This is a significant advancement in the ability to track medication adherence. In 
particular, when a dose is missed, a participant can be contacted within a time frame that 
maximizes the likelihood of maintaining steady-state medication levels, which should translate to 
increased sensitivity to medication effects. The Wisepill® digital monitoring system is currently 


being used in other studies conducted in our facility. Maintenance medications (i.e., DUL-MTH 
combinations) will be self-administered by participants once daily at approximately 0900h for the 
duration of the trial. The use of once-daily dosing formulations of the constituent compounds will 
improve adherence when advanced to clinical trials or practice. 
The dosing regimen described above will be reversed to taper DUL and MTH. During the first 
week after discharge participants in the 60 mg/day DUL cohort will be maintained on 30 mg/day 
DUL and 20 mg/day MTH and 20 mg/day DUL and 10 mg/day MTH during the second week 
following discharge. Participants in the 0 mg/day DUL cohort will be maintained on 0 mg/day DUL 
and 20 mg/day MTH in the first week and 0 mg/day DUL and 10 mg/day MTH during the second 
week following discharge.  All participants will be scheduled for the final follow-up visit 1 week 
after discontinuing DUL and MTH (as described below).  
All participants, whether or not they complete the study, will be scheduled for follow-up visits 
1-, 2- and 3-weeks following discharge. Participants will complete the laboratory screening 
procedures used during screening for study participation (e.g., laboratory chemistry values). 
These laboratory tests, including liver function, used for study inclusion will be repeated the day 
following discharge (Day 29) on participants who finish or drop out. If elevated liver enzymes are 
detected, we will follow them until they return to normal and consult with our study physicians on 
a course of action. In addition, a questionnaire used on Research Electronic Data Capture 
(REDCap), a secure, web-based application designed to support efficient, secure and confidential 
data collection for clinical research. The REDCap questionnaire will to assess recent activities 
(e.g., sleep quality, past 24 h alcohol and drug use, ALC craving) and the emergence of adverse 
events. At each follow-up visits the Timeline Followback (TLFB) questionnaire, also administered 
electronically, will be used to assess the quantity of alcohol use during the past week. Participants 
will be paid $50 for each follow-up visit. 
Monitoring Adverse Events. Once daily during medication maintenance, participants will 
complete the REDCap questionnaire (the same questionnaire described above) to assess recent 
activities (e.g., sleep quality, past 24 h alcohol and drug use, ALC craving) and the emergence of 
adverse events during medication maintenance.  Participants will be asked whether they have 
experienced any of the side effects listed in the informed consent document. If they endorse any 
side effects, they will be asked to rate the severity and whether they believe it was related to the 
study medication. They will also have the opportunity to report other side effects not included in 
the questionnaire. A staff member will verify that the questionnaire has been completed at the 
appropriate approximate time, and contact the study physician and PI if any significant side effects 
are noted. We are using similar procedures to monitor side effects in ongoing projects. During 
experimental sessions, adverse events will be monitored via observations by the medical and 
research staff, spontaneous report by the participants, regular measurement of cardiovascular 
indices and use of the UKU Side Effects Rating Scale and subjective effects questionnaires. 
Chronic users are more likely to tolerate acute intoxication and are less likely to be impaired under 
acute dose. 
Apparatus. Participants will come to the LHBP on the day that each of the 5 sessions (i.e., 1 
practice; 4 experimental) are completed. During these sessions, participants will not be permitted 
to leave the LHBP premises, nor will visitors be allowed. Upon arrival to the LHBP, the LHBP staff 
will also take the participant’s car keys and will return them when the participant is released from 
the LHBP two hours after ALC consumption and upon provision of a BAL that is below 0.02 g/dl. 
Should the participant leave the LHBP prior to that time, the LHBP staff or participant will arrange 
alternate transportation (e.g., arrange a taxi). The car keys will be returned to participants after 
ensuring that alternate transportation for the participant has been confirmed (e.g., taxi driver has 
arrived at the LHBP premises). 
Participants will be tested in individual rooms in order to eliminate the effects of social factors 


on the behavioral and physiological effects of ALC. Participants will complete experimental tasks 
on a laptop computer. The computer records the data and relays them to the participant’s 
respective file where they are stored. This computer system automates the collection of 
behavioral data, increasing the efficiency and accuracy of data collection and management.  
On session days, participants will arrive at the LHBP at approximately 1400h. Urine toxicology, 
ADHD and depression ratings, expired breath samples for BAL determination will be obtained. A 
field sobriety test will be administered to confirm sobriety. Presence of riboflavin in the urine will 
be verified using a hand-held ultraviolet light detector. Participants whose urine does not fluoresce 
will not be permitted to proceed with the scheduled experimental session and any subsequent 
experimental sessions, and will be dropped from the study. Time of maintenance dosing will be 
confirmed by self-report and Wisepill® log. Following completion of the above-mentioned 
procedures, participants will be provided a standardized light snack. Participants will report their 
ALC consumption and craving in the natural environment during each 6-day maintenance block 
using the REDCap questionnaire. As outlined in Table 2, self-reported ALC craving, subjective 
effects questionnaires and inhibitory control tasks will be completed at 1500h (i.e., baseline). 
 
Time 
Table 2: Experimental Session Activities 
1400-1500h 
Arrival to LHBP. Urinalysis, BAL samples, field sobriety, vitals, and self-reported time 
of maintenance dosing. Participant provided a light standardized snack. 
1500-1530h 
Baseline measures (e.g., BAL samples; vitals; ALC craving; subjective effects 
questionnaires; ABBA; Hypothetical Delay Discounting; Purchase Tasks). 
1545-1615h 
ALC Sampling (i.e., single administration of ALC designed to raise BALs to 0.03 g/dl). 
BAL, ALC craving, and subjective effects determined at 10, 20, and 30 min. ABBA, 
Hypothetical Delay Discounting, and Purchase Tasks completed at 30 min. 
1645h 
BAL sample collected, ALC craving and subjective effects, vitals assessed. 
1715h 
BAL sample collected, ALC craving and subjective effects, vitals assessed. 
1745h 
BAL sample collected, ALC craving and subjective effects, vitals assessed. 
1800h 
BAL sample collected, vitals assessed, field sobriety test, and discharge from LHBP 
(receive maintenance medication in the Wisepill® device or taper doses if last 
experimental session, payment, and car keys). 
 
 
ALC Dose. Participants will consume the ALC dose at approximately 1545h during 
experimental sessions to acquaint them with ALC effects. Participants will receive a single 
administration of 95% ALC mixed with non-alcoholic mixer (e.g., lemon lime soda, tonic water) 
(designed to raise BALs to 0.03 g/dl), to be consumed over 5 minutes. The measures of interest 
are described below in the following paragraphs.  
ALC Craving. A single, reliable and valid instrument, the Penn Alcohol Craving Scale, will be 
used to measure craving during the experimental sessions described above and in the natural 
ecology during the medication maintenance phases. 
Subjective-Effects Questionnaires. Five subjective-effects questionnaires that measure 
various aspects of mood and ALC effects will be used: 1) Subjective High Assessment Scale 
(SHAS); 2) a Drug-Effect Questionnaire (DEQ) modified for use with ALC; 3) Biphasic ALC Effects 
Scale; 4) Profile of Mood States (POMS); and 5) Snaith-Hamilton Pleasure Scale (SHAPS). 


Inhibitory Control Measures. Inhibitory control measures include: 1) ABBA (see Appendix A) 
and 2) Hypothetical Delay Discounting (see Appendix B). These tasks are completed at baseline 
and after the sampling dose of ALC. 
Commodity Purchase Tasks (Appendix C). Commodity purchase tasks will be used to assess 
economic demand for alcohol and soda (Amlung et al., 2015; Bruner and Johnson, 2014; Murphy 
and MacKillop, 2006; Strickland and Stoops, 2017). In these tasks, participants are asked to 
indicate the hypothetical number of items (e.g., one alcoholic drink) they would purchase at a 
range of monetary increments (e.g., $0.00 [free] to $15/drink). All choices are hypothetical and 
will not be purchased or administered. Data from the commodity purchase task will be analyzed 
using economic demand equations previously applied to purchase task data (e.g., Strickland et 
al., 2016). Primary outcomes of this task include elasticity of demand (α) and intensity of demand 
(Q0). 
ALC Use in the Natural Ecology. ALC use in the natural ecology will be assessed daily for 
each maintenance period using the REDCap and prior to each of the experimental sessions in 
order to construct of calendar of ALC use during maintenance. The TLFB questionnaire will be 
administered electronically and will be used during the practice session and at each of the three 
follow-up visits. 
Safety and Tolerability Measures. Physiological measures (i.e., BAL measurements, heart 
rate and blood pressure) will be recorded upon arrival at the LHBP, before ALC administration 
and throughout the session at the intervals noted in Table 2 using digital monitors. ALC will not 
be administered if a participant’s heart rate is ≥100 bpm, systolic pressure is ≥150 mmHg or 
diastolic pressure is ≥100 mmHg. A participant will be excluded from further participation if he/she 
exhibits hypersensitivity (i.e., heart rate > 130 bpm, systolic pressure > 180 mmHg, diastolic 
pressure > 120 mmHg) during maintenance on MTH and DUL and/or to the effects of ALC. The 
UKU Side Effects Rating Scale will be completed at the end of sessions (Lingjaerde et al., 1987). 
 
Data Analysis 
Data will be analyzed as raw scores. Statistical significance refers to p ≤ 0.05. 
Demographics. Demographic data from each DUL cohort (0 or 60 mg/day) will be compared 
using unpaired t-tests. Should the cohorts differ on any demographic variables (e.g., subclinical 
levels of ADHD and depression), they will be used as covariates in subsequent statistical 
analyses. ADHD and depression will be re-determined during each of the experimental sessions 
allowing us to determine changes as a function of maintenance condition and whether these 
changes impact subjective, physiological, or cognitive-behavioral changes following ALC 
consumption. 
Outcome Measures. ALC craving during the experimental session, physiological, and 
subjective responses (i.e., Subjective High Assessment Scale; Drug-Effect Questionnaire; 
Biphasic ALC Effects Scale; Profile of Mood States; and Snaith-Hamilton Pleasure Scale) 
following consumption of the ALC dose will be analyzed similarly as peak effect (i.e., maximum 
effect observed following the ALC sampling dose) and area-under-the-time-action curve (AUC; 
calculated for each participant using the trapezoidal method). These data will be analyzed with 
two-factor mixed-model ANOVA with DUL (between-subject variable; 0 or 60 mg/day) and MTH 
(within-subject variable; 0, 20, 40, 60 mg/day) as the factors. A significant attenuation (e.g., 
decreased ALC craving) will be inferred if the main effect of DUL or MTH, or the interaction of 
DUL and MTH attains statistical significance in the ANOVA. If the DUL-MTH interaction attains 
statistical significance, the mean square error term will be used to conduct Tukey’s HSD post-hoc 
test to make appropriate pair-wise comparisons between means. Naturalistic ALC use and 
craving will be used to determine if the effects of the DUL-MTH combinations are additive, supra-


additive or infra-additive (i.e., isobolographic analysis). Naturalistic ALC use and craving (group 
mean and standard error) under a dose combination will be considered: 1) additive if it overlaps 
with the arithmetic sum of the effects observed under the DUL and MTH doses alone; 2) supra-
additive if it is greater than the sum of the individual dose alone and without overlap; or 3) infra-
additive if it is less than the sum of the effects of the individual doses alone and without overlap.  
Data from the ABBA (i.e., proportion of inhibitory failures to no-go targets following ALC go 
cues, reaction time to go targets following go cues), Hypothetical Delay Discounting (k values), 
commodity purchase tasks (elasticity of demand [α] and intensity of demand [Q0]) will be analyzed 
using mixed-model ANOVAs with the factors described above, but with time (pre- vs. post-alcohol-
challenge). A significant improvement will be inferred if the main effect of DUL or MTH, the 
interaction of DUL and MTH, or the interaction of DUL, MTH and Time attains statistical 
significance in the ANOVA. If the DUL-MTH-Time interaction attains statistical significance, the 
mean square error term will be used to conduct Tukey’s HSD post-hoc test to make appropriate 
pair-wise comparisons between means. Outcomes from the commodity purchase tasks will also 
be correlated with subjective effect and physiological data to explore the mechanisms by which 
MTH and DUL attenuate the effects of the ALC challenge.  
Power and Sample Size Considerations. In light of the modifications as of June 2020 and 
given that a mixed-model design is still being used,  we anticipate enrolling 16 participants in each 
DUL cohort (2 cohort, n = 32 participants) will provide sufficient statistical power to detect changes 
in naturalistic ALC use, ALC craving, and the behavioral, subjective, and physiological responses 
to an ALC challenge. The new total sample size is supported by the ‘One in Ten Rule’ (Harrell et 
al., 1984) wherein 10 participants are needed for each predictor. Within the context of this study 
(3 predictors: DUL cohorts, MTH dose, and time [e.g., pre- vs post-alcohol-challenge]). 
Participants that do not complete will be replaced in order to ensure adequate statistical power to 
detect the hypothesized effects.  
 
 


APPENDIX A 
 
Attentional Bias-Behavioral Activation Task 
 
Instructions (read to the participant before task) 
 
This is a reaction time task that I would like you to perform. While you are performing the 
task, please place your right index finger on the key that has the green sticker. 
 
Presented on the screen will be squares that are green or blue in color. If the color GREEN 
appears on the screen, you are to press the green button as quickly as possible. If the color 
BLUE appears on the screen, then no response is required. Now, before the green or blue color 
appears, you will see a plus sign in the middle of the screen. It serves as a fixation point so that 
you know where to focus your attention on the computer screen. After the plus sign disappears, 
a picture will appear on the screen. The pictures are of various objects. Do not respond to any 
picture. They are just there to get you ready to respond to the target colors of GREEN and BLUE 
when they appear. Again, if the color GREEN appears, respond as quickly as possible by 
pressing the green key. If the color BLUE appears, then no response is required.  
 
Any questions about that? 
 
To help you to respond quickly, the computer will display how fast you are pressing the key when 
the target appears. Once you respond to a green target, the screen will show you the amount of 
time it took for you to make that response, in milliseconds (the fewer milliseconds, the faster the 
response). So lower numbers are better. If you accidentally respond to a blue target, the screen 
will say ‘Incorrect Response’. 
 
Any questions about that? 
 
So just to recap, if the color GREEN appears, press the green key as quickly as possible. You 
are always trying to respond in the shortest time – the fewest milliseconds. If the color BLUE 
appears, no response is required. 
 
The time to complete this test is about 15 minutes that includes 4 breaks. Please pay attention to 
the task throughout the entire session and try not to become distracted. In the breaks, a beep will 
sound when there are 10 seconds left on the break so that you may get ready to start again.  I 
will stay in the room with you for the beginning of the task to make sure that you have 
understood the instructions and that there are no problems, so please just ignore me and do not 
talk while performing the task. Once you are underway, I will leave. When the test is over, please 
open the door and have a seat so that I will know that you are done. 
 
Any questions? Are you ready to begin? OK, I am going to start the task, so remember to 
respond as quickly as possible and do your best.


Appendix B 
 
5-Trial Adjusting Delay Discounting Task (Table from Koffarnus and Bickel 2014) 
 
The below table describes the outcomes for the 5-trial task. For each of the 5 choices (i.e., No.), 
the participant is asked if the would prefer the immediate or delayed reinforcer. The delay to the 
delayed choice is systematically increased or decreased based on previous trial choice (i.e., 
Delay Choice; increases if delay is chosen, decreases if immediate is chosen). The primary 
outcome is k as labeled in the table below. 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 


Appendix C 
 
Commodity Purchase Task 
 
Example Instructions for Participants 
 
This is a series of questions designed to assess choices for alcohol across changes in price. This 
information is entirely for research purposes. All questions about purchasing are completely 
hypothetical (pretend). 
 
Imagine a TYPICAL DAY during which you drink alcohol. The following questions ask how much 
alcohol you would consume if it cost various amounts of money. The alcohol is your preferred 
brand and type (e.g., beer, wine, liquor). Assume that each drink is a standard drink (i.e., 12 oz. 
beer, 5 oz. wine, 1.5 oz. shot alone or in mixed drink). Assume that you have the same income 
that you have now and NO ACCESS to any alcohol products than those offered at these prices. 
In addition, assume that you would consume all the alcohol you purchase on that day; that is you 
cannot save or stockpile any for a later date. 
 
Example Questions for Participants (for the Alcohol Purchase Task 
 
Price/Drink 
# Drinks Purchased 
Free 
 
$0.02 
 
$0.05 
 
$0.13 
 
$0.25 
 
$0.50 
 
$1.00 
 
$2.00 
 
$3.00 
 
$4.00 
 
$5.00 
 


$6.00 
 
$7.00 
 
$8.00 
 
$9.00 
 
$10.00 
 
$11.00 
 
$12.00 
 
$13.00 
 
$14.00 
 
$15.00 
 
 
 
 
 

ICF_002.pdf: 
Page 1 of 13 
 
Combined Consent and Authorization to Participate in a Research Study 
 
           KEY INFORMATION FOR BEHAVIORAL EFFECTS OF DRUGS: INPATIENT (36) 
 
 
You are being invited to take part in a research study about the effects of drugs on behavior. You are being asked 
to participate because you are 21-55 years old with a recent history of alcohol use (i.e., have used alcohol in the 
past week). You are also being asked to participate because you have expressed interest in participating in this 
study, you passed the medical screen and it is unlikely that you will react badly to the laboratory setting or to the 
drugs you will take. 
WHAT IS THE PURPOSE, PROCEDURES, AND DURATION OF THIS STUDY? 
 
This medication development experiment is testing the effects of methylphenidate (a medication used to treat 
Attention Deficit Hyperactivity Disorder [ADHD]), duloxetine (a medication used to treat depression) and their 
combination on the subjective and physiological effects of alcohol. We are also interested in determining whether 
methylphenidate, duloxetine or their combination impacts whether you like alcohol and want to choose to drink it.  
Your participation in this research will last about eight weeks. The research procedures will be conducted in the 
Laboratory of Human Behavioral Pharmacology (LHBP) at the University of Kentucky. During the time you 
participate, you must agree to participate as an outpatient at the LHBP. You will be asked to complete 1 practice 
session, 4 experimental session days, and 3 post-study follow-ups. 
The purpose of this research is to gather information on the safety and effectiveness of methylphenidate, 
duloxetine, and their combination on the behavioral, subjective and physiological effects of alcohol. 
WHAT ARE REASONS YOU MIGHT CHOOSE TO VOLUNTEER FOR THIS STUDY?  
 
Understand that you are not a patient receiving medical treatment and that you will not receive any direct benefits 
from this study. However, the knowledge gained will contribute to a better understanding of the nature of effects of 
these drugs and may result in improved therapeutic treatments for patients taking these drugs. If you are seeking 
treatment, please notify the investigator now and he will make the necessary referral. For a complete description 
of benefits, refer to the Detailed Consent. 
WHAT ARE REASONS YOU MIGHT CHOOSE NOT TO VOLUNTEER FOR THIS STUDY?  
 
The primary risks to participation are those specifically related to the ingestion of the study drugs. Two types of 
risk are associated with the administration of these drugs to human volunteers. First, the drugs under study 
occasionally produce side effects. The drugs will be administered in combination, which may change the side 
effect profile. Second, there is a slight risk that habituation or tolerance will develop. If you develop habituation or 
tolerance to the medications administered in the study, the effects of these medications would be decreased if 
they were administered to you at therapeutic doses. For a complete description of risks, refer to the Detailed 
Consent.  
If you do not want to be in the study, there are no other choices except not to take part in the study. 
DO YOU HAVE TO TAKE PART IN THE STUDY? 
If you decide to take part in the study, it should be because you really want to volunteer. You will not lose any 
services, benefits or rights you would normally have if you choose not to volunteer.  
WHAT IF YOU HAVE QUESTIONS, SUGGESTIONS OR CONCERNS? 
The person in charge of this study is Craig R. Rush, Ph.D. of the University of Kentucky, Departments of 
Behavioral Science, Psychiatry, and Psychology.  If you have questions, suggestions, or concerns regarding this 
study or you want to withdraw from the study his contact information is: 859-257-5388 
If you have any questions, suggestions or concerns about your rights as a volunteer in this research, contact staff 
in the University of Kentucky (UK) Office of Research Integrity (ORI) between the business hours of 8am and 5pm 
EST, Monday-Friday at 859-257-9428 or toll free at 1-866-400-9428. 
IRB Approval
2/15/2023
IRB # 44796
IRB3


Page 2 of 13 
 
DETAILED CONSENT: 
 
ARE THERE REASONS WHY YOU WOULD NOT QUALIFY FOR THIS STUDY? 
You should not participate if you have a history of serious physical disease, current physical 
disease, impaired cardiovascular functioning, high blood pressure, chronic obstructive pulmonary 
disease, history of epilepsy or seizure, diabetes, current or past histories of serious psychiatric disorder. 
You should not participate if you have a history of other significant medical problems. You should not 
participate if you are seeking treatment for your alcohol or drug use, are currently in treatment for your 
alcohol or drug use, or are currently in successful remission from your alcohol or drug use. If you have 
ever been addicted to alcohol or drugs, you should discuss this with the research staff before agreeing 
to participate. 
If you are a female, you should not participate if you are pregnant or plan on becoming pregnant 
during your participation in this experiment. You must be using an effective form of birth control (e.g. 
birth control pills, surgically sterilized, IUD, cervical cap with a spermicide, condoms or abstinence), and 
you must be willing to take a pregnancy test before being accepted into the research study. You will 
also be required to take a pregnancy test prior to each experimental session. Should one of these tests 
show that you are pregnant, your participation will be terminated immediately. If you are female, you 
should not participate if you are lactating or breast feeding a baby. 
 
WHERE IS THE STUDY GOING TO TAKE PLACE AND HOW LONG WILL IT LAST? 
The research procedures will be conducted at the University of Kentucky Laboratory of Human 
Behavioral Pharmacology (LHBP). Your participation in this study will last approximately one month and 
a half as outlined in Table 1 contained in the Appendix. During the time you participate, you must agree 
to participate as an outpatient at the LHBP. You will be asked to complete 1 practice session, 4 
experimental session days, and 3 post-study follow ups. You must agree to follow the general rules of 
the LHBP. You should understand that during the time that you spend at the LHBP that you will not be 
allowed to leave the office unsupervised, nor will you be allowed to have visitors. You will not be 
allowed to make telephone calls during the practice and experimental sessions, and the follow-ups. 
 
WHAT WILL YOU BE ASKED TO DO? 
Before participating in this research study, it will be necessary for you to have a physical and 
psychiatric examination. During the time you participate, you must agree to participate as an outpatient 
at the LHBP for 1 practice, 4 experimental sessions, and 3 post-study follow-ups over approximately 1 
month and a half. During the time you participate, you should refrain from using any illicit substances. 
Also, please refrain from drinking alcohol 12 hours prior to coming to the laboratory and consuming 
food or caffeine 4 hours prior to a session. The first session will be a “practice” session to make you 
familiar with the various tasks and procedures of the experiment as outlined in Table 2 in the Appendix. 
The remaining experimental sessions will occur following periods of taking a maintenance medication. 
Sessions will last approximately 4 hours each, but you will be asked to stay as an outpatient at the 
LHBP until you are no longer affected by any of the alcohol you consume. During the sessions, we will 
collect data concerning your physiological status and your subjective status. That is, we will record your 
heart rate, blood pressure, and temperature. We will also repeatedly ask you to answer various 
questionnaires about how you feel and about what kind of drug effect you feel. The scheduled tasks 
pose no hazard or risk to you. You must agree to complete these forms and to do the tasks to the best 
of your ability and at the scheduled times. At the end of sessions, you will be paid the $40 for 
completing the session and the adherence bonus for that week during medication maintenance 
(described on page 5). In the evening after each session, you will be discharged from the LHBP, 
provided that you meet appropriate release criteria (i.e., pass a sobriety test and have a breath alcohol 
level below 0.02 g/dl). On the day following from the last experimental session (Day 29) or following 
your last day of study participation – should you choose to withdraw from the study early– (described in 
Table 2), research staff will escort to the University of Kentucky Medical Center to undergo additional 
medical screening. It will be necessary to take a small amount of blood from a vein in your arm (i.e., 
about 1 ounce or 35 ml). You will be scheduled for an appointment that would best suit your schedule. 
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This appointment is anticipated to last approximately 1 hour. These tests will be used to determine if 
your heart, kidney, liver, and immune system function are normal. These tests, however, will not allow 
us to detect the presence or absence of specific diseases (for example, hepatitis). If your liver enzymes 
are abnormal, you will be notified and the study physicians will be notified for consultation on a course 
of action. The investigators may request repeat tests until your liver enzymes return to normal. If 
desired, copies of these tests may be provided to you.   
During the active treatment phase (i.e., drug maintenance periods of the study), you will be given a 
device called a Wisepill® that will contain medications for you to take and that will monitor when you 
take the medication. We ask that you take the medication at the specified time (i.e., 9:00 AM) and that 
you return the device to us undamaged and in good working condition. We ask that you take that 
medication at the time specified. All study medications will also be encapsulated with the dietary 
supplement riboflavin to assess adherence via fluorescence detection. Presence of riboflavin in a 
provided urine sample will be verified prior to experimental sessions using a hand-held ultraviolet light 
detector. 
During your participation, you should not use any illicit drug. There will be urine checks and 
breathalyzers prior to each experimental session. These urine and breath checks will be conducted at 
the LHBP. If a urine screen or breathalyzer shows that you used other drugs or you have them in your 
possession, you may be dropped from the study. If you are dropped from the study because you used 
other drugs, or had them in your possession, you may lose portions of your completion bonus money 
you could have earned. 
Daily experimental procedures. On your first session, you will complete a practice session. This 
practice session is to familiarize you with the experimental routine. Every other session will be an 
experimental session. If you smoke tobacco cigarettes, you should understand that you will not be 
allowed to smoke during the practice or experimental session which will last approximately 4 hours. We 
have included a table in the Appendix to help you better understand the study protocol. 
Drugs and Drug Administration.  During the experiment you will be given doses of commonly 
prescribed drugs or recreational drugs. Drugs will be administered by mouth.  The drugs tested will be 
placebo (an inactive substance, no drug), an ADHD medication (methylphenidate [Metadate CD®]), an 
anti-depressant (duloxetine [Cymbalta®]), and alcohol. The prescription drugs will be administered in 
doses approved by the Food and Drug Administration (FDA). These drugs will be administered alone 
and in combination.   
 
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS? 
The physiological measures, cognitive-behavioral tasks, and subjective-effects questionnaires 
present no risks exceeding those of everyday experience. The primary risks to participation are those 
specifically related to the ingestion of the study drugs. The drugs under study occasionally produces 
side effects and these are outlined in the Appendix tables. We will monitor for these side effects during 
experimental sessions at the LHBP and while you are taking these medications on an outpatient basis. 
If you feel you are experiencing any of these side effects, you should tell the research staff or physician. 
In addition to the risks listed in the Appendix, you may experience a previously unknown risk or side 
effect. 
As noted above, it will be necessary to take a small amount of blood from a vein in your arm. You 
may experience some discomfort from having the needle inserted into the vein in your arm. There is 
some risk of bruising, soreness, infection, bleeding, pain, irritation from the insertion of the need in to 
the vein in your arm. However, these risks are minimal since standard sterile procedures will be used. 
You should be aware that some people faint while blood is being taken.  
 
WILL YOU BENEFIT FROM TAKING PART IN THIS STUDY? 
Understand that you are not a patient receiving medical treatment and that you will not receive 
any direct benefits from this study. However, the knowledge gained will contribute to a better 
understanding of alcohol effects and may result in improved therapeutic treatments. If you are seeking 
treatment, please notify the investigator now and he will make the necessary referral. 
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WHAT WILL IT COST YOU TO PARTICIPATE? 
Participating in this research study will not cost you anything. The clinical laboratory tests, physical 
examination and psychiatric screen described above will be paid by a grant from the National Institute 
on Alcohol Abuse and Alcoholism (NIAAA). The University of Kentucky may not be allowed to bill your 
insurance company, Medicare or Medicaid for the medical procedures done strictly for research. 
Therefore, these costs will be paid by the sponsor (the NIAAA). 
You and/or your insurance company, Medicare or Medicaid will be responsible for the costs of all 
care and treatment you receive during this study that you would normally receive for your condition. 
These are costs that are considered medically reasonable and necessary and will be part of the care 
you receive if you do not take part in this study. 
 
WHO WILL SEE THE INFORMATION THAT YOU GIVE? 
Every effort will be made to maintain the confidentiality of your study records. The data from the 
study may be published; however, you will not be identified by name. Your identity will remain 
confidential, unless you give prior written approval or unless it meets our disclosure criteria (i.e., about 
communicable diseases, abuse of a child or elderly person or that you intend to harm yourself or 
others). Your name, address, and social security number will be listed on the receipt for payment that 
you receive, as required by the Internal Revenue Service; but no information about your participation in 
this research project will be released. We will be collecting your social security number for payment 
purposes. You cannot participate in this research if you withhold your social security number. 
This research is covered by a Certificate of Confidentiality from the National Institutes of Health. 
The researchers with this Certificate may not disclose or use information, documents, or biospecimens 
that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other 
action, suit, or proceeding, or be used as evidence, for example, if there is a court subpoena, unless 
you have consented for this use. Information, documents, or biospecimens protected by this Certificate 
cannot be disclosed to anyone else who is not connected with the research except, if there is a federal, 
state, or local law that requires disclosure (such as to report child abuse or communicable diseases but 
not for federal, state, or local civil, criminal, administrative, legislative, or other proceedings, see below); 
if you have consented to the disclosure, including for your medical treatment; or if it is used for other 
scientific research, as allowed by federal regulations protecting research subjects. 
The Certificate cannot be used to refuse a request for information from personnel of the United 
States federal or state government agency sponsoring the project that is needed for auditing or 
program evaluation by National Institute of Health (NIH) which is funding this project or for information 
that must be disclosed in order to meet the requirements of the federal Food and Drug Administration 
(FDA).  You should understand that a Certificate of Confidentiality does not prevent you from voluntarily 
releasing information about yourself or your involvement in this research. If you want your research 
information released to an insurer, medical care provider, or any other person not connected with the 
research, you must provide consent to allow the researchers to release it. 
 
CAN YOU CHOOSE TO WITHDRAW FROM THE STUDY EARLY? 
You can discontinue your participation in this study at any time. If you choose to withdraw from the 
study, you will be required to remain in the facility until the investigators are satisfied that you are no 
longer affected by the drug. During this time, you will be free to spend your time engaged in activities 
that are not part of the study. You should understand that you must remain in the facility in order to 
protect yourself and others from the effects of the drug and that your judgment while you are affected 
by the drug may be impaired sufficiently to necessitate that you remain in the facility.  
You should understand, however, that if you decide to withdraw from the study early you will not 
receive any of the completion allowance described below. You will receive the $40 per session 
completion allowance for each of the experimental sessions you completed.  
You should understand the principal investigator on this project, Craig R. Rush, Ph.D., can terminate 
your participation for the following reasons: 1) failure to adhere to subject rules for the LHBP, 2) if you 
44796


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verbally or physically assault another volunteer, patient, or staff member at the LHBP, 3) if your 
behavior is disruptive to other ongoing studies that are conducted at the LHBP, 4) if your behavior is 
disruptive to the other volunteers, patients, research staff, or medical staff at the LHBP, 5) failure to 
comply with the alcohol, drug, and food restrictions, 6) failure to comply with the pregnancy restrictions, 
7) failure to take the doses as prescribed or complete a scheduled experimental session, 8) failure to 
perform the behavioral tasks to the best of your ability, 9) if you leave the LHBP against the advice of 
the principal investigator or the medical doctors. If you are terminated for any of these reasons, it will be 
deemed that you did not complete all of your scheduled experimental sessions and you will not receive 
the completion allowance described below. 
You should also understand that the medical doctors on this project, Lon R. Hays, MD, M.B.A. and 
Abner O. Rayapati, M.D., can terminate your participation if they do not feel that it is medically safe for 
you to continue. If your participation is terminated for medical reasons, you will receive the $40/session 
completion allowance for each of the experimental sessions you completed. 
If you choose to withdraw from the study early, the data collected until that point will remain in 
the study database and may not be removed. The individuals conducting the study may need to 
withdraw you from the study and the study intervention and/or medication will no longer be provided by 
the investigator and may not be accessible commercially. This may occur if you are not able to follow 
the directions they give you, if they find that your being in the study is more risk than benefit to you, or if 
the agency funding the study decides to stop the study early for a variety of scientific reasons. It is not 
expected that withdrawing from the study will lead to risks in your health and welfare, but investigators 
may request follow up appointments if you withdraw. 
 
ARE YOU PARTICIPATING, OR CAN YOU PARTICIPATE, IN ANOTHER RESEARCH STUDY AT 
THE SAME TIME AS PARTICIPATING IN THIS ONE? 
You may not take part in this study if you are currently involved in another research study. It is 
important to let the investigator/your doctor know if you are in another research study. You should also 
discuss with the investigator before you agree to participate in another research study while you are 
enrolled in this study. 
 
WHAT HAPPENS IF YOU GET HURT OR SICK DURING THE STUDY? 
If you believe you are hurt or if you get sick because of something that is due to the study, you 
should call Lon R. Hays, M.D., M.B.A. at (859) 323-6021 x 79015 or Abner O. Rayapati, M.D. at (859) 
257-9175 immediately. You can also call 911 in the case of an emergency. Dr. Hays or Dr. Rayapati 
will determine what type of treatment, if any, is best for you at that time. The medical costs related to 
your care and treatment because of research related harm will be your responsibility. It is important for 
you to understand that the University of Kentucky does not have funds set aside to pay for the cost of 
any care or treatment that might be necessary because you get hurt or sick while taking part in this 
study. Also, the University of Kentucky will not pay for any wages you may lose if you are harmed by 
this study.  
You do not give up your legal rights by signing this form. 
 
WILL YOU RECEIVE ANY REWARDS FOR TAKING PART IN THIS STUDY? 
You will be paid for your participation in this experiment. You will earn payments for attending visits, 
making certain selections during experimental sessions, and taking medications as directed.  
Specifically, you will earn $40 for each practice and experimental session that you finish. This will be 
paid to you upon completing that session. If you complete the entire study (i.e., complete 1 practice 
session and 4 experimental sessions over approximately one month), you will earn an additional $40 
per session bonus after the end of the study on Day 29 (see Table 1 in appendix). Thus, the maximum 
amount of money you can earn from completing practice and experimental sessions is $400.  
You will also earn money if you take the doses given to you as prescribed. Specifically, on the first 
day of maintenance that you take your doses at 9:00 AM, as verified by the Wisepill®, you will earn $5 
for that day. For each consecutive day that you take doses as prescribed, that payment will increase by 
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$2 (e.g., you will earn $7 on the second day in a row that you take your doses at 9:00 AM as verified by 
the Wisepill®). You will also receive $50 for each of the three post-study follow up appointments that 
you attend. 
If you complete the entire study, attending each visit as scheduled and taking each dose as 
directed, you can earn up to approximately $1,446.  
You should understand that if you make more than a total of $600 by participating in research 
projects, the University of Kentucky will report your earnings to the appropriate state and federal 
government agencies (i.e., Internal Revenue Service [IRS]). You should further understand that it is 
your responsibility to determine how these earnings might affect your personal financial situation. 
 
WHAT IF NEW INFORMATION IS LEARNED DURING THE STUDY THAT MIGHT AFFECT YOUR 
DECISION TO PARTICIPATE? 
If the investigators on this project, Craig R. Rush, Ph.D., William W. Stoops, Ph.D., Joshua A. Lile, 
Ph.D., Lon R. Hays, MD, M.B.A. and Abner O. Rayapati, M.D. learn of new information in regards to 
this study, and it might change your willingness to stay in this study, the information will be provided to 
you. You may be asked to sign a new informed consent form if the information is provided to you after 
you have joined the study. If you choose not to continue, you will not lose any of your earnings. That is, 
you will receive the completion allowance for each of the experimental sessions you completed. 
 
WILL YOU BE GIVEN INDIVIDUAL RESULTS FROM THE RESEARCH TESTS? 
 
Do you give permission for Craig R. Rush, Ph.D. to contact you with information about research results 
or  incidental findings that are determined to be important to you/your family’s health? (Incidental findings 
are unforeseen findings discovered during the course of the research that may affect you or your 
family’s health). 
p 
Yes       
p 
No          _________Initials 
You may also withdraw your consent to be contacted with information about research results or 
incidental findings by sending a written request to Craig R. Rush, Ph.D. 465 E. High Street, Suite 204B, 
Lexington, KY 40507. 
 
WHAT ELSE DO YOU NEED TO KNOW? 
This research is supported by a grant from the National Institute on Alcohol Abuse and Alcoholism 
(NIAAA [DA 026255]). 
 
If you volunteer to take part in this research, you will be one of about 40 people to do so 
nationally, and one of about 40 to do so at the University of Kentucky. 
 
The information that you are providing will no longer belong to you. The research may lead to 
new clinical or educational knowledge, tests, treatments, or products. These products could have some 
financial value. There are no plans to provide financial payment to you or your relatives if this occurs. 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. 
 
WILL YOUR INFORMATION (OR SPECIMEN SAMPLES) BE USED FOR FUTURE RESEARCH? 
Your information or samples collected for this study will NOT be used or shared for future research 
studies, even if we remove the identifiable information like your name, medical record number, or date 
of birth.  
 
 
 
 
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AUTHORIZATION TO USE OR DISCLOSE YOUR IDENTIFIABLE HEALTH INFORMATION  
The privacy law, HIPAA (Health Insurance Portability and Accountability Act), requires 
researchers to protect your health information. This form describes how researchers may use your 
information. Please read it carefully.  
 
Your health information will be used and/or released (disclosed) for the following research 
study: Behavioral Effects of Drugs (Inpatient): 36 (Alcohol, Methylphenidate, and Duloxetine). 
• 
      You allow Craig R. Rush, Ph.D. and his research staff at the University of Kentucky to 
create, access, use and release your health information for the purposes listed below.  
 
Your health information that may be used and released includes: 
• 
Demographic information (for example, information about your race, gender, socioeconomic 
status, and age) pertaining to the study. 
• 
Results of physical examinations pertaining to the study. 
• 
Results of psychiatric screening tests pertaining to the study. 
• 
Results of questionnaires and study procedures pertaining to the study. 
• 
Results of blood tests and urine screens pertaining to the study. 
• 
Medical history pertaining to the study. 
 
Your health information will be used for: 
• 
A study coordinated by Craig R. Rush, Ph.D. examining the effects of alcohol. Your 
protected health information is necessary to conduct this line of research, as well as to meet 
legal, institutional, and accreditation requirements. 
 
The Researchers may use and share your health information with: 
• 
The University of Kentucky’s Institutional Review Board/Office of Research Integrity, 
• 
University of Kentucky Medical Center, Investigational Drug Service, Center for Clinical and 
Translational Sciences, Clinical Research Unit, and Clinical Research Organization,  
• 
The National Institute on Alcohol Abuse and Alcoholism, 
• 
The Food and Drug Administration 
 
If you become pregnant anytime during the study or within 7 days after stopping the study drug, 
you must inform the study doctor. The study doctor must then report the outcome of your pregnancy to 
the Sponsor (and/or the FDA). 
The researchers agree to only share your health information with the people listed in this 
document.  
Should your health information be released to anyone that is not regulated by the privacy law, 
your health information may be shared with others without your permission; however, the use of your 
health information would still be regulated by applicable federal and state laws.  
 
You will not be allowed to participate in the research study if you do not sign this form. If you 
decide not to sign the form, it will not affect your: 
• 
Current or future healthcare at the University of Kentucky 
• 
Current or future payments to the University of Kentucky  
• 
Ability to enroll in any health plans (if applicable) 
• 
Eligibility for benefits (if applicable) 
 
 
 
 
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After signing the form, you can change your mind and NOT let the researcher(s) release or use 
your health information (revoke the Authorization). If your revoke the authorization: 
 
• 
You will send a written letter to: Craig R. Rush, Ph.D. 465 E. High Street, Suite 204B, Lexington, 
KY 40507 to inform him of your decision. 
• 
Researchers may use and release your health information already collected for this research 
study. 
• 
Your protected health information may still be used and released should you have a bad 
reaction (adverse event). 
• 
You will not be allowed to participate in the study. 
 
If you have not already received a copy of the Privacy Notice, you may request one. If you have 
any questions about your privacy rights, you should contact the University of Kentucky’s 
Privacy Officer between the business hours of 8am and 5pm EST, Monday-Friday at (859) 323-
1184. 
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Appendix: Study Visits/Procedures  
WHAT WILL YOU BE ASKED TO DO? 
Day 
Table 1: Experimental Procedures 
0 
Practice Session at the LHBP. The timeline of this session matches that of experimental 
sessions (see Table 2 below). 
1-6 
Drug maintenance. On Day 1, you will take your oral dose of methylphenidate, duloxetine, 
and/or placebo at approximately 9:00 AM and continue through Day 6. Doses will be provided in 
a Wisepill® device that will monitor when you take the doses. 
7 
Experimental Session 1 at the LHBP. The Experimental Session timeline is outlined in Table 2. 
8-13 
Drug maintenance on your oral dose of methylphenidate, duloxetine, and/or placebo. As 
described in Days 1 – 6.  
14 
Experimental Session 2 at the LHBP.  
15-20 
Drug maintenance on your oral dose of methylphenidate, duloxetine, and/or placebo. As 
described in Days 1 – 6. 
21 
Experimental Session 3 at the LHBP. 
22-27 
Drug maintenance on your oral dose of methylphenidate, duloxetine, and/or placebo. As 
described in Days 1 – 6. 
28 
Experimental Session 4 at the LHBP. Following discharge, you will receive taper medications to 
take for 2 weeks that you will being taking on morning of Day 29. 
29 + 3 
weeks 
Medical screening repeated on Day 29. Follow-up visits scheduled weekly for 3 weeks following 
participation. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Day 
Table 2: Experimental Session Activities 
2:00-3:00 PM 
Arrival at the LHBP. If you drove to the LHBP, your car keys will be collected. Urine 
sample collected and analyzed for drugs for all and pregnancy for females. Breath 
alcohol level, field sobriety test, vital signs assessment, self-reported times of 
maintenance dosing, questionnaires about drug and alcohol use completed. You will 
need to abstain from alcohol for at least 12 hours prior to your arrival at the LHBP. 
3:00-3:30 PM Baseline subjective, physiological and cognitive-behavioural measures completed. 
3:45-4:15 PM 
 During this time, you will sample a dose of alcohol. Subjective and physiological 
measures will be completed at 10, 20, and 30 minutes after this sample dose. 
Cognitive-behavioral measures will be completed 30 minutes after this sample dose.  
4:45 PM 
Subjective and physiological measures will be completed. 
5:15 PM 
Subjective and physiological measures will be completed. 
5:45 PM 
Subjective and physiological measures will be completed. 
6:00 PM 
Physiological measures collected. After passing the sobriety test and having a breath 
alcohol level below 0.02 mg/dL, you will receive the WisePill®  device containing your 
doses for the next 7 days (or taper doses no if last experimental session), your 
payment, and your car keys, and will be discharged from the LHBP  
 
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Appendix: Risks 
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS? 
 
Possible Risk or  
Side Effect of Alcohol 
How often has it 
occurred? 
How serious is it? 
Can it be corrected? 
Drowsiness, slurred speech, 
headache, gastrointestinal 
upset, breathing difficulties, 
distorted vision and hearing, 
impaired judgment and 
decreased perception and 
coordination 
These are likely 
to or will occur. 
Somewhat serious 
These side effects are 
likely to decrease over time 
as the medications clear 
from your system. 
Blackouts (memory lapses, 
where the drinker cannot 
remember events that 
occurred while under the 
influence), anemia, 
unconsciousness and 
coma 
These are 
extremely 
uncommon. 
Very Serious 
No. 
 
 
Possible Risk or 
Side Effect of 
Methylphenidate 
How often has it 
Occurred? 
How Serious is it? 
Can it be Corrected? 
anxiety, restlessness, 
difficulty sleeping, loss 
of appetite, changes in 
heart rate, dizziness, 
faintness, irritability, 
shaking, nausea or other 
gastrointestinal 
discomfort, headache, 
increased blood 
pressure, performance 
impairment, flushing and 
sweating 
These are likely to 
or will occur. 
Somewhat serious. 
These side effects are 
likely to decrease over time 
as the medications clear 
from your system. 
heart attack, stroke, 
psychotic episodes, 
seizure, death 
These are extremely 
uncommon. 
Very Serious 
No 
 
 
 
 
 
 
 
 
 
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Possible Risk or  
Side Effect of duloxetine 
How often has it 
occurred? 
How serious is it? 
Can it be corrected? 
changes in vision, 
agitation, anxiety, body 
aches or pain, cough, 
dizziness/lightheadedness, 
constipation, diarrhea, 
difficulty with breathing, 
dry mouth, ear congestion, 
changes in urination, 
headache, fainting, 
increased blood pressure, 
weakness, loss of 
appetite, loss of voice, 
muscle aches, nausea, 
nervousness, rash, 
itchiness, changes in 
sexual function, sleepiness 
or unusual drowsiness, 
sleeplessness, sneezing, 
sore throat, swelling, stuffy 
or runny nose, sweating, 
tremor and weight change 
These commonly 
occur. 
Somewhat serious 
These side effects are 
likely to decrease over 
time as the medications 
clear from your system. 
angle-closure 
glaucoma, 
unusual bruising/bleeding, 
seizures, 
hallucinations, 
worsening 
of 
existing 
depression 
or 
suicidal 
thoughts 
and 
Stevens-
Johnson syndrome.  
 
These are extreme- 
ly uncommon. 
Very serious 
These may go away with 
treatment. 
  
 
 
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