CClinicalTrials.gg
CompletedNCT03575403BED[IN]:36Updated Jun 9, 2026Results posted

Behavioral Effects of Drugs: Inpatient (36) (Alcohol, Duloxetine, and Methylphenidate)

A Phase 1 interventional study of Alcohol and Placebos in Alcohol Use Disorder, sponsored by Craig Rush. Completed at 1 site in United States. Open to participants aged 21 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-09.

Sponsored by Craig Rush · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
19
Allocation
Randomized
Ages
21 Years to 55 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Alcohol Use Disorder

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03

Who can participate

Ages eligible
21 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • able to speak/read English
  • not seeking treatment at the time of the study
  • one binge drinking episode (5+/4+ standard alcoholic drinks per drinking session for men and women, respectively) in the past 30 days
  • recent alcohol use verified by ethyl glucuronide positive urine, as well as fulfillment of DSM-5 diagnostic criteria for alcohol use disorder
  • ECG within normal limits
  • otherwise healthy
  • body mass index of 19-35
  • females using an effective form of birth control and not pregnant or breast feeding
  • judged by the medical staff to be psychiatrically and physically healthy
  • able to abstain from alcohol for 12 hours prior to session

Exclusion criteria

Exclusion Criteria

  • Not under 21 years of age or over 55 years of age
  • no contraindications/allergies to alcohol, duloxetine, or methylphenidate
04

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Factorial assignment
Masking
Triple (Participant, Care provider, Outcomes assessor)
Enrollment
19 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Subjects received oral placebo capsules one time daily.

    Drug: Alcohol · Drug: Placebos · Drug: Methylphenidate

  • Experimental
    Duloxetine (60 MG)

    Subjects received 60 mg of oral duloxetine one time daily.

    Drug: Duloxetine (60 MG)

  • Experimental
    Duloxetine (30 MG)

    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.

    Drug: Duloxetine (30 MG)

Interventions

  • DrugAlcohol

    In each arm and during sessions, subjects will receive doses of alcohol designed to raise breath alcohol levels (BAL) to 0.03 g/dl.

  • DrugPlacebos

    Subjects will receive oral placebo capsules.

  • DrugDuloxetine (60 MG)

    Subjects will receive 60-mg of oral duloxetine capsules.

  • DrugMethylphenidate

    Subjects will receive methylphenidate capsules.

  • DrugDuloxetine (30 MG)

    Subjects will receive 30-mg of oral duloxetine capsules.

05

What researchers measure

Primary outcomes

  1. Reinforcing Effects (Pre-Alcohol Dose Consumption)

    The reinforcing effects of alcohol will be determined using a alcohol purchase task procedure in which subjects will report the number of alcohol drinks they would purchase across changes in price. The questions that were asked were completely hypothetical. The reinforcing effects are measured during experimental session maintenance on methylphenidate and placebo or duloxetine. These data represent "alpha", which a rate measure of sensitivity to changes in price: greater values represent great sensitivity to price changes. These data were collected prior to consumption of the alcohol dose. There is no minimum or maximum value.

    Time frame: Measured at each methylphenidate dose-level over approximately four weeks of participation.

  2. Reinforcing Effects (Post-Alcohol Dose Consumption)

    The reinforcing effects of alcohol will be determined using a alcohol purchase procedure in which subjects will report the number of alcohol drinks they would purchase across changes in price. The questions that were asked were completely hypothetical. The reinforcing effects are measured during experimental session maintenance on methylphenidate and placebo or duloxetine. These data represent "alpha", which a rate measure of sensitivity to changes in price: greater values represent great sensitivity to price changes. These data were collected following consumption of the alcohol dose. There is no minimum or maximum value.

    Time frame: Measured at each methylphenidate dose-level over approximately four weeks of participation.

Secondary outcomes

  1. Visual Analog Scales of Alcohol Effects Following Methylphenidate (0 mg) Maintenance.

    Subjects will complete measures using visual analog scales rated from 0-100 mm to report alcohol effects during four experimental sessions. These items will ask about alcohol effects. Higher scores indicate greater effects. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of oral alcohol

    Time frame: Measured at each methylphenidate dose-level over approximately four weeks of participation.

  2. Visual Analog Scales of Alcohol Effects Following Methylphenidate (20 mg) Maintenance.

    Subjects will complete measures using visual analog scales rated from 0-100 mm to report alcohol effects during four experimental sessions. These items will ask about alcohol effects. Higher scores indicate greater effects. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of oral alcohol

    Time frame: Measured at each methylphenidate dose-level over approximately four weeks of participation.

  3. Visual Analog Scales of Alcohol Effects Following Methylphenidate (40 mg) Maintenance.

    Subjects will complete measures using visual analog scales rated from 0-100 mm to report alcohol effects during four experimental sessions. These items will ask about alcohol effects. Higher scores indicate greater effects. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of oral alcohol

    Time frame: Measured at each methylphenidate dose-level over approximately four weeks of participation.

  4. Visual Analog Scales of Alcohol Effects Following Methylphenidate (60 mg) Maintenance.

    Subjects will complete measures using visual analog scales rated from 0-100 mm to report alcohol effects during four experimental sessions. These items will ask about alcohol effects. Higher scores indicate greater effects. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of oral alcohol

    Time frame: Measured at each methylphenidate dose-level over approximately four weeks of participation.

  5. Breath Alcohol Level

    Expired air samples for determining breath alcohol level (BAL) will be recorded during four experimental sessions. BALs were recorded as g/dl. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of oral alcohol. Greater values of BAL represent more alcohol absorbed following consumption.

    Time frame: Measured at each methylphenidate dose-level over approximately four weeks of participation.

  6. Systolic Blood Pressure

    Systolic blood pressure (millimeter of mercury) was recorded during four experimental sessions. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of oral alcohol.

    Time frame: Measured at each methylphenidate dose-level over approximately four weeks of participation.

  7. Diastolic Blood Pressure

    Diastolic blood pressure (millimeter of mercury) was recorded during four experimental sessions. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of oral alcohol.

    Time frame: Measured at each methylphenidate dose-level over approximately four weeks of participation.

  8. Heart Rate

    Heart rate (beats per minute) will be recorded during four experimental sessions. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of oral alcohol.

    Time frame: Measured at each methylphenidate dose-level over approximately four weeks of participation.

06

Results

Posted Apr 10, 2025

Participant flow

Participant flow — Overall Study
MilestonePlaceboDuloxetine (30 MG)Duloxetine (60 MG)
Started1126
0 mg methylphenidate1126
20 mg methylphenidate1026
40 mg methylphenidate1026
60 mg methylphenidate926
Completed926
Not completed200
Withdrew: Adverse event100
Withdrew: One subject left due to personal reasons unrelated to study-procedures100

Outcome measures

PrimaryReinforcing Effects (Pre-Alcohol Dose Consumption)

The reinforcing effects of alcohol will be determined using a alcohol purchase task procedure in which subjects will report the number of alcohol drinks they would purchase across changes in price. The questions that were asked were completely hypothetical. The reinforcing effects are measured during experimental session maintenance on methylphenidate and placebo or duloxetine. These data represent "alpha", which a rate measure of sensitivity to changes in price: greater values represent great sensitivity to price changes. These data were collected prior to consumption of the alcohol dose. There is no minimum or maximum value.

Time frame:
Measured at each methylphenidate dose-level over approximately four weeks of participation.
Reported as:
Mean · Units on a Theoretical Scale
Reinforcing Effects (Pre-Alcohol Dose Consumption)
Units on a Theoretical ScalePlaceboDuloxetine 30 mgDuloxetine (60 MG)
Methylphenidate (0 mg)0.005 (0.0043 to 0.0057).01 (0.0078 to 0.012)0.007 (0.005 to 0.008)
Methylphenidate (20 mg)0.005 (0.0041 to 0.0058).02 (0.014 to 0.020)0.007 (0.006 to 0.009)
Methylphenidate (40 mg)0.005 (0.0041 to 0.0057)0.014 (0.012 to 0.018)0.007 (0.006 to 0.008)
Methylphenidate (60 mg)0.005 (0.0041 to 0.0057).02 (0.012 to 0.020)0.008 (0.006 to 0.009)
PrimaryReinforcing Effects (Post-Alcohol Dose Consumption)

The reinforcing effects of alcohol will be determined using a alcohol purchase procedure in which subjects will report the number of alcohol drinks they would purchase across changes in price. The questions that were asked were completely hypothetical. The reinforcing effects are measured during experimental session maintenance on methylphenidate and placebo or duloxetine. These data represent "alpha", which a rate measure of sensitivity to changes in price: greater values represent great sensitivity to price changes. These data were collected following consumption of the alcohol dose. There is no minimum or maximum value.

Time frame:
Measured at each methylphenidate dose-level over approximately four weeks of participation.
Reported as:
Mean · Units on a Theoretical Scale
Reinforcing Effects (Post-Alcohol Dose Consumption)
Units on a Theoretical ScalePlaceboDuloxetine (30 MG)Duloxetine (60 MG)
Methylphenidate (0 mg)0.004 (0.0038 to 0.0052).01 (0.0075 to 0.010)0.006 (0.005 to 0.008)
Methylphenidate (20 mg)0.005 (0.0041 to 0.0054).01 (0.010 to 0.013)0.007 (0.005 to 0.008)
Methylphenidate (40 mg)0.005 (0.0039 to 0.0053).014 (0.011 to 0.017)0.006 (0.005 to 0.008)
Methylphenidate (60 mg)0.005 (0.0044 to 0.0056).01 (0.010 to 0.016)0.009 (0.007 to 0.011)
SecondaryVisual Analog Scales of Alcohol Effects Following Methylphenidate (0 mg) Maintenance.

Subjects will complete measures using visual analog scales rated from 0-100 mm to report alcohol effects during four experimental sessions. These items will ask about alcohol effects. Higher scores indicate greater effects. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of oral alcohol

Time frame:
Measured at each methylphenidate dose-level over approximately four weeks of participation.
Reported as:
Mean · units on a scale
Visual Analog Scales of Alcohol Effects Following Methylphenidate (0 mg) Maintenance.
units on a scalePlaceboDuloxetine (30 MG)Duloxetine (60 MG)
Feel Drink15.89 ± 15.454.50 ± 2.1222.00 ± 17.34
Feel High0.11 ± 0.331.00 ± 1.412.00 ± 3.95
Like Drink12.33 ± 16.084.50 ± 0.7125.33 ± 20.30
Want Drink17.22 ± 17.487.50 ± 0.7123.50 ± 20.42
SecondaryVisual Analog Scales of Alcohol Effects Following Methylphenidate (20 mg) Maintenance.

Subjects will complete measures using visual analog scales rated from 0-100 mm to report alcohol effects during four experimental sessions. These items will ask about alcohol effects. Higher scores indicate greater effects. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of oral alcohol

Time frame:
Measured at each methylphenidate dose-level over approximately four weeks of participation.
Reported as:
Mean · units on a scale
Visual Analog Scales of Alcohol Effects Following Methylphenidate (20 mg) Maintenance.
units on a scalePlaceboDuloxetine (30 MG)Duloxetine (60 MG)
Feel Drink17.44 ± 11.6810.50 ± 6.3628.50 ± 20.11
Feel High0.22 ± 0.671.50 ± 2.121.83 ± 4.02
Like Drink16.78 ± 23.559.50 ± 6.3627.33 ± 22.14
Want Drink19.22 ± 19.5715.50 ± 4.9532.33 ± 24.66
SecondaryVisual Analog Scales of Alcohol Effects Following Methylphenidate (40 mg) Maintenance.

Subjects will complete measures using visual analog scales rated from 0-100 mm to report alcohol effects during four experimental sessions. These items will ask about alcohol effects. Higher scores indicate greater effects. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of oral alcohol

Time frame:
Measured at each methylphenidate dose-level over approximately four weeks of participation.
Reported as:
Mean · units on a scale
Visual Analog Scales of Alcohol Effects Following Methylphenidate (40 mg) Maintenance.
units on a scalePlaceboDuloxetine (30 MG)Duloxetine (60 MG)
Feel Drink10.67 ± 8.797.50 ± 2.1220.17 ± 11.50
Feel High0.11 ± 0.331.00 ± 1.412.50 ± 4.18
Like Drink16.89 ± 21.9710.00 ± 1.4124.00 ± 18.28
Want Drink11.11 ± 12.5815.00 ± 0.0026.00 ± 27.31
SecondaryVisual Analog Scales of Alcohol Effects Following Methylphenidate (60 mg) Maintenance.

Subjects will complete measures using visual analog scales rated from 0-100 mm to report alcohol effects during four experimental sessions. These items will ask about alcohol effects. Higher scores indicate greater effects. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of oral alcohol

Time frame:
Measured at each methylphenidate dose-level over approximately four weeks of participation.
Reported as:
Mean · units on a scale
Visual Analog Scales of Alcohol Effects Following Methylphenidate (60 mg) Maintenance.
units on a scalePlaceboDuloxetine (30 MG)Duloxetine (60 MG)
Feel Drink12.67 ± 10.975.50 ± 2.1217.17 ± 13.83
Feel High0.11 ± 0.331.00 ± 1.411.17 ± 2.40
Like Drink10.78 ± 12.778.00 ± 0.0020.50 ± 21.14
Want Drink8.44 ± 13.6015.00 ± 1.4115.17 ± 11.48
SecondaryBreath Alcohol Level

Expired air samples for determining breath alcohol level (BAL) will be recorded during four experimental sessions. BALs were recorded as g/dl. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of oral alcohol. Greater values of BAL represent more alcohol absorbed following consumption.

Time frame:
Measured at each methylphenidate dose-level over approximately four weeks of participation.
Reported as:
Mean · g/dl
Breath Alcohol Level
g/dlPlaceboDuloxetine (30 MG)Duloxetine (60 MG)
Methylphenidate (0 mg)0.026 ± 0.0140.031 ± 0.0060.029 ± 0.013
Methylphenidate (20 mg)0.024 ± 0.0060.031 ± 0.0040.042 ± 0.030
Methylphenidate (40 mg)0.024 ± 0.0080.041 ± 0.0060.034 ± 0.021
Methylphenidate (60 mg)0.026 ± 0.0070.023 ± 0.0050.037 ± 0.015
SecondarySystolic Blood Pressure

Systolic blood pressure (millimeter of mercury) was recorded during four experimental sessions. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of oral alcohol.

Time frame:
Measured at each methylphenidate dose-level over approximately four weeks of participation.
Reported as:
Mean · Millimeters of mercury
Systolic Blood Pressure
Millimeters of mercuryPlaceboDuloxetine (30 MG)Duloxetine (60 MG)
Methylphenidate (0 mg)125.00 ± 13.65129.00 ± 19.80124.00 ± 8.90
Methylphenidate (20 mg)126.67 ± 12.35140.00 ± 9.90121.67 ± 6.53
Methylphenidate (40 mg)123.33 ± 10.39130.00 ± 18.38124.33 ± 8.73
Methylphenidate (60 mg)125.44 ± 12.17131.50 ± 9.19127.50 ± 11.98
SecondaryDiastolic Blood Pressure

Diastolic blood pressure (millimeter of mercury) was recorded during four experimental sessions. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of oral alcohol.

Time frame:
Measured at each methylphenidate dose-level over approximately four weeks of participation.
Reported as:
Mean · Millimeter of mercury
Diastolic Blood Pressure
Millimeter of mercuryPlaceboDuloxetine (30 MG)Duloxetine (60 MG)
Methylphenidate (0 mg)73.56 ± 10.1782.00 ± 12.7377.67 ± 6.71
Methylphenidate (20 mg)74.00 ± 9.4988.50 ± 6.3677.00 ± 8.51
Methylphenidate (40 mg)74.22 ± 7.0885.50 ± 9.1980.33 ± 5.09
Methylphenidate (60 mg)74.00 ± 8.8982.00 ± 8.4980.50 ± 9.14
SecondaryHeart Rate

Heart rate (beats per minute) will be recorded during four experimental sessions. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of oral alcohol.

Time frame:
Measured at each methylphenidate dose-level over approximately four weeks of participation.
Reported as:
Mean · Beats per minute
Heart Rate
Beats per minutePlaceboDuloxetine (30 MG)Duloxetine (60 MG)
Methylphenidate (0 mg)75.89 ± 11.4766.50 ± 4.9575.83 ± 11.41
Methylphenidate (20 mg)83.44 ± 12.6380.50 ± 3.5484.83 ± 11.43
Methylphenidate (40 mg)81.67 ± 7.4873.50 ± 2.1288.83 ± 13.01
Methylphenidate (60 mg)83.89 ± 13.0480.50 ± 2.1298.50 ± 21.72

Adverse events

Collected over Four weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/11 (0%)0/11 (0%)11/11 (100%)
Duloxetine (30 MG)0/2 (0%)0/2 (0%)2/2 (100%)
Duloxetine (60 MG)0/6 (0%)0/6 (0%)6/6 (100%)
Most frequent other events
Showing 10 of 32
Most frequent other events
EventPlaceboDuloxetine (30 MG)Duloxetine (60 MG)
AnxietyNervous system disorders3/112/23/6
Body AchesMusculoskeletal and connective tissue disorders2/112/20/6
DizzinessNervous system disorders0/112/21/6
DiarrheaGastrointestinal disorders5/112/22/6
HeadacheGeneral disorders4/112/23/6
Muscle AchesMusculoskeletal and connective tissue disorders1/112/20/6
NauseaGeneral disorders2/112/23/6
Sleepiness/DowsinessGeneral disorders2/112/22/6
Sore ThroatGeneral disorders2/112/21/6
RestlessnessGeneral disorders3/112/23/6

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)PlaceboDuloxetine (30 MG)Duloxetine (60 MG)Total
<=18 years0000
Between 18 and 65 years112619
>=65 years0000
Age, Continuous
Age, Continuous(years)PlaceboDuloxetine (30 MG)Duloxetine (60 MG)Total
Mean31.27 ± 9.0032.50 ± 13.4430.25 ± 10.6630.48 ± 9.46
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboDuloxetine (30 MG)Duloxetine (60 MG)Total
Female5038
Male62311
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboDuloxetine (30 MG)Duloxetine (60 MG)Total
American Indian or Alaska Native0000
Asian0000
Native Hawaiian or Other Pacific Islander0000
Black or African American1001
White92617
More than one race1001
Unknown or Not Reported0000
Region of Enrollment
Region of Enrollment(participants)PlaceboDuloxetine (30 MG)Duloxetine (60 MG)Total
United States112619
07

Study locations

1 site
  • University of Kentucky
    Lexington, Kentucky 40511, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · May 31, 2018
  • Informed consent form · Feb 15, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03575403
Lead sponsor
Craig Rush
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Responsible party
Craig Rush (Professor, University of Kentucky) — Sponsor-investigator
First posted
Jul 2, 2018
Start date
Sep 1, 2018
Primary completion
Mar 15, 2023
Completion
Mar 15, 2023
Results posted
Apr 10, 2025
Last update
Jun 9, 2026

Study contacts

Craig Rush, PhD
principal investigator · University of Kentucky

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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