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

Phase 1

Completed

Conditions: Alcohol Use Disorder

Interventions: Drug: Alcohol
Drug: Duloxetine (60 MG)
Drug: Duloxetine (30 MG)
Drug: Placebos
Drug: Methylphenidate

Registration Number: NCT03575403

Lead Sponsor: Craig Rush

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

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

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Alcohol	Subjects received oral placebo capsules one time daily.
Placebo	Placebos	Subjects received oral placebo capsules one time daily.
Placebo	Methylphenidate	Subjects received oral placebo capsules one time daily.
Duloxetine (60 MG)	Duloxetine (60 MG)	Subjects received 60 mg of oral duloxetine one time daily.
Duloxetine (30 MG)	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.

Primary Outcome Measures

Name	Time	Method
Reinforcing Effects (Pre-Alcohol Dose Consumption)	Measured at each methylphenidate dose-level over approximately four weeks of participation.	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.
Reinforcing Effects (Post-Alcohol Dose Consumption)	Measured at each methylphenidate dose-level over approximately four weeks of participation.	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.

Secondary Outcome Measures

Name	Time	Method
Visual Analog Scales of Alcohol Effects Following Methylphenidate (0 mg) Maintenance.	Measured at each methylphenidate dose-level over approximately four weeks of participation.	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
Visual Analog Scales of Alcohol Effects Following Methylphenidate (20 mg) Maintenance.	Measured at each methylphenidate dose-level over approximately four weeks of participation.	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
Visual Analog Scales of Alcohol Effects Following Methylphenidate (40 mg) Maintenance.	Measured at each methylphenidate dose-level over approximately four weeks of participation.	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
Visual Analog Scales of Alcohol Effects Following Methylphenidate (60 mg) Maintenance.	Measured at each methylphenidate dose-level over approximately four weeks of participation.	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
Breath Alcohol Level	Measured at each methylphenidate dose-level over approximately four weeks of participation.	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.
Systolic Blood Pressure	Measured at each methylphenidate dose-level over approximately four weeks of participation.	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.
Diastolic Blood Pressure	Measured at each methylphenidate dose-level over approximately four weeks of participation.	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.
Heart Rate	Measured at each methylphenidate dose-level over approximately four weeks of participation.	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.