Behavioral Effects of Drugs: Inpatient (36) (Alcohol, Duloxetine, and Methylphenidate) (BED[IN]:36)

A Novel Drug Combination for Alcohol-Use Disorders: A Human Laboratory Study

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.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Methylphenidate; Drug: Alcohol; Drug: Placebos; Drug: Duloxetine (60 MG); Drug: Duloxetine (30 MG)

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40511
      • University Of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects received oral placebo capsules one time daily.	Drug: Methylphenidate; Subjects will receive methylphenidate capsules.; Drug: Alcohol; In each arm and during sessions, subjects will receive doses of alcohol designed to raise breath alcohol levels (BAL) to 0.03 g/dl.; Drug: Placebos; Subjects will receive oral placebo capsules.
Experimental: Duloxetine (60 MG); Subjects received 60 mg of oral duloxetine one time daily.	Drug: Duloxetine (60 MG); Subjects will receive 60-mg of oral duloxetine capsules.
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); Subjects will receive 30-mg of oral duloxetine capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Measured at each methylphenidate dose-level over approximately four weeks of participation.
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.	Measured at each methylphenidate dose-level over approximately four weeks of participation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Measured at each methylphenidate dose-level over approximately four weeks of participation.
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	Measured at each methylphenidate dose-level over approximately four weeks of participation.
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	Measured at each methylphenidate dose-level over approximately four weeks of participation.
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	Measured at each methylphenidate dose-level over approximately four weeks of participation.
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.	Measured at each methylphenidate dose-level over approximately four weeks of participation.
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.	Measured at each methylphenidate dose-level over approximately four weeks of participation.
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.	Measured at each methylphenidate dose-level over approximately four weeks of participation.
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.	Measured at each methylphenidate dose-level over approximately four weeks of participation.

Collaborators and Investigators

• Sponsor: Craig Rush
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Craig Rush, PhD, University Of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): March 15, 2023
• Study Completion (Actual): March 15, 2023

Study Registration Dates

• First Submitted: June 22, 2018
• First Submitted That Met QC Criteria: June 29, 2018
• First Posted (Actual): July 2, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Alcoholism; Alcohol Drinking; Serotonin and Noradrenaline Reuptake Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Sensory System Agents; Analgesics; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Central Nervous System Stimulants; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Dopamine Agents; Antidepressive Agents; Duloxetine Hydrochloride; Methylphenidate
• Other Study ID Numbers: 44796; R01AA026255 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No