Behavioral Effects of Drugs: Inpatient (35) (BED IN 35)

Influence of Methylphenidate and Duloxetine Maintenance on Pharmacodynamic Effects of Cocaine

This study will determine the influence of methylphenidate (Metadate®) and duloxetine (Cymbalta®), alone and in combination, on the reinforcing, subjective and physiological effects of cocaine.

Study Overview

• Status: Completed
• Conditions: Cocaine Use Disorder
• Intervention / Treatment: Drug: Methylphenidate; Drug: Cocaine; Drug: Placebo oral capsule

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0086
      • University of Kentucky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recent cocaine use

Exclusion Criteria:

• Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant
• Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion
• History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation
• Females not currently using effective birth control
• Contraindications to cocaine, methylphenidate or duloxetine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Subjects will be maintained on oral placebo. Subjects will be maintained on placebo and methylphenidate during placebo maintenance. Cocaine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance.	Drug: Methylphenidate; The pharmacodynamic effects of methylphenidate maintenance will be determined during maintenance on placebo and duloxetine.; Other Names: Metadate®; Drug: Cocaine; The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and duloxetine.; Drug: Placebo oral capsule; The pharmacodynamic effects of placebo will be determined during maintenance on placebo and duloxetine.
ACTIVE_COMPARATOR: Duloxetine; Subjects will be maintained on oral duloxetine. Subjects will be maintained on duloxetine and methylphenidate during placebo maintenance. Cocaine will be administered acutely during duloxetine maintenance. Placebo will be administered acutely during duloxetine maintenance.	Drug: Methylphenidate; The pharmacodynamic effects of methylphenidate maintenance will be determined during maintenance on placebo and duloxetine.; Other Names: Metadate®; Drug: Cocaine; The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and duloxetine.; Drug: Placebo oral capsule; The pharmacodynamic effects of placebo will be determined during maintenance on placebo and duloxetine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reinforcing Effects of Cocaine Following Placebo Maintenance.	Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.	Following at least 4 days of maintenance on placebo during inpatient admission.
Reinforcing Effects of Cocaine Following Duloxetine Maintenance.	Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.	Following at least 4 days of maintenance on duloxetine during inpatient admission.
Reinforcing Effects of Cocaine Following Methylphenidate Maintenance.	Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.	Following at least 4 days of maintenance on duloxetine during inpatient admission.
Reinforcing Effects of Cocaine Following Methylphenidate and Duloxetine Maintenance.	Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.	Following at least 4 days of maintenance on methylphenidate and duloxetine during inpatient admission.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjective Rating Scale-Sedative	Subjects will complete the adjective rating scale during nine sessions while they are admitted to our inpatient unit. Responses to 16 items are summed (total score=0-64; Higher values=more sedation) to calculate scores on a sedative subscale.	Nine times over approximately four weeks inpatient admission.
Adjective Rating Scale-Stimulant	Subjects will complete the adjective rating scale during nine sessions while they are admitted to our inpatient unit. Responses to 16 items are summed (total score=0-64; Higher values=more stimulation) to calculate total scores on a stimulant subscale.	Nine times over approximately four weeks inpatient admission.
Drug Effect Questionnaire	Subjects will complete the drug effect questionnaire during nine sessions while they are admitted to our inpatient unit. The items (total scores=0-100; Higher scores=greater drug effect) on this scale categorize the constellation of drug effects endorsed by subjects.	Nine times over approximately four weeks inpatient admission.
Heart rate	Beats per minute. Measured daily during inpatient admission.	Daily over approximately four week inpatient admissions.
Blood pressure	mmHg.Measured daily during inpatient admission.	Daily over approximately four week inpatient admissions.
Temperature	Degrees fahrenheit. Measured daily during inpatient admission.	Daily over approximately four week inpatient admissions.
Side effects	Subjects will complete a side effects questionnaire daily while they reside on the inpatient unit. Side Effects questions will query subjects about common effects of centrally active medications.	Daily over approximately four week inpatient admissions.
Delay Discounting Task	Subjects will complete the delay discounting task during nine sessions while they are admitted to our inpatient unit. Responses will be used to calculate discounting slope (i.e., K).	Nine times over approximately four weeks inpatient admission.
Attentional Bias	Subjects will complete attentional bias during nine sessions while they are admitted to our inpatient unit. Time attending to drug stimuli will be used to evaluate attentional bias.	Nine times over approximately four weeks inpatient admission.
Inhibitory Control	Subjects will complete an inhibitory control task during nine sessions while they are admitted to our inpatient unit. Ability to inhibit prepotent responding will be used to calculate inhibitory control.	Nine times over approximately four weeks inpatient admission.

Collaborators and Investigators

• Sponsor: Craig Rush
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2018
• Primary Completion (ACTUAL): May 31, 2019
• Study Completion (ACTUAL): May 31, 2019

Study Registration Dates

• First Submitted: April 11, 2018
• First Submitted That Met QC Criteria: April 25, 2018
• First Posted (ACTUAL): May 8, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 25, 2019
• Last Update Submitted That Met QC Criteria: June 24, 2019
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Anesthetics, Local; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Vasoconstrictor Agents; Methylphenidate; Cocaine
• Other Study ID Numbers: 43500

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