Behavioral Effects of Drugs (Inpatient): 40 [Methamphetamine, Methylphenidate, Duloxetine]

Sponsor

Craig Rush (Other)

Overall Status

Completed

CT.gov ID

NCT04178993

Collaborator

National Institute on Drug Abuse (NIDA) (NIH)

Enrollment

Locations

Arms

20.1

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Methamphetamine Use Disorder	Drug: Methamphetamine Drug: Methylphenidate Drug: Placebo oral capsule Drug: Duloxetine	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

A Novel Drug Combination as a Pharmacotherapeutic for Methamphetamine-Use Disorder

Actual Study Start Date :

Sep 1, 2019

Actual Primary Completion Date :

May 5, 2021

Actual Study Completion Date :

May 5, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Comparator: Placebo Subjects will be maintained on oral placebo. Subjects will be maintained on placebo and methylphenidate during placebo maintenance. Methamphetamine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance.	Drug: Methamphetamine In each arm, subjects will receive doses of methamphetamine. Other Names: Metamfetamine Drug: Methylphenidate In each arm, subjects will receive methylphenidate capsules. Other Names: Metadate® Drug: Placebo oral capsule In each arm, subjects will receive placebo capsules. Other Names: Lactose
Active Comparator: Active Comparator: Duloxetine Subjects will be maintained on oral duloxetine. Subjects will be maintained on duloxetine and methylphenidate during placebo maintenance. Methamphetamine will be administered acutely during duloxetine maintenance. Placebo will be administered acutely during duloxetine maintenance.	Drug: Methamphetamine In each arm, subjects will receive doses of methamphetamine. Other Names: Metamfetamine Drug: Methylphenidate In each arm, subjects will receive methylphenidate capsules. Other Names: Metadate® Drug: Placebo oral capsule In each arm, subjects will receive placebo capsules. Other Names: Lactose Drug: Duloxetine Subjects will receive duloxetine capsules in the duloxetine arm. Other Names: Cymbalta®

Arm

Intervention/Treatment

Placebo Comparator: Placebo Comparator: Placebo

Subjects will be maintained on oral placebo. Subjects will be maintained on placebo and methylphenidate during placebo maintenance. Methamphetamine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance.

Drug: Methamphetamine

In each arm, subjects will receive doses of methamphetamine.

Other Names:

Metamfetamine

Drug: Methylphenidate

In each arm, subjects will receive methylphenidate capsules.

Other Names:

Metadate®

Drug: Placebo oral capsule

In each arm, subjects will receive placebo capsules.

Other Names:

Lactose

Active Comparator: Active Comparator: Duloxetine

Subjects will be maintained on oral duloxetine. Subjects will be maintained on duloxetine and methylphenidate during placebo maintenance. Methamphetamine will be administered acutely during duloxetine maintenance. Placebo will be administered acutely during duloxetine maintenance.

Drug: Methamphetamine

In each arm, subjects will receive doses of methamphetamine.

Other Names:

Metamfetamine

Drug: Methylphenidate

In each arm, subjects will receive methylphenidate capsules.

Other Names:

Metadate®

Drug: Placebo oral capsule

In each arm, subjects will receive placebo capsules.

Other Names:

Lactose

Drug: Duloxetine

Subjects will receive duloxetine capsules in the duloxetine arm.

Other Names:

Cymbalta®

Outcome Measures

Primary Outcome Measures

Reinforcing Effects of Methamphetamine Following Placebo Maintenance. [Following at least 4 days of maintenance on placebo during inpatient admission]
Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement.
Reinforcing Effects of Methamphetamine Following Duloxetine Maintenance. [Following at least 4 days of maintenance on duloxetine during inpatient admission]
Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement.
Reinforcing Effects of Methamphetamine Following Methylphenidate Maintenance. [Following at least 4 days of maintenance on methylphenidate during inpatient admission]
Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement.
Reinforcing Effects of Methylphenidate Following Methylphenidate and Duloxetine Maintenance [Following at least 4 days of maintenance on methylphenidate and duloxetine during inpatient admission.]
Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement

Secondary Outcome Measures

Drug Effect Questionnaire [12 sessions over approximately 4.5 weeks of study participation]
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.
Heart rate [Daily over approximately 4.5 weeks of inpatient stay.]
Beats per minute. Measured daily during inpatient admission.
Blood pressure [Daily over approximately 4.5 weeks of inpatient stay.]
mmHg.Measured daily during inpatient admission.
Temperature [Daily over approximately 4.5 weeks of inpatient stay.]
Degrees fahrenheit. Measured daily during inpatient admission.
Side effects [Daily over approximately 4.5 weeks of inpatient stay.]
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.

Other Outcome Measures

Attentional Bias [12 sessions over approximately 4.5 weeks of study participation]
Subjects will complete attentional bias during 12 sessions while they are admitted to our inpatient unit. Time attending to drug stimuli will be used to evaluate attentional bias.
Delay Discounting Task [12 sessions over approximately 4.5 weeks of study participation]
Subjects will complete the delay discounting task during twelve sessions while they are admitted to our inpatient unit. Responses will be used to calculate discounting slope (i.e., K).
Anhedonia (Inability to experience pleasure) [12 sessions over approximately 4.5 weeks of study participation]
A 14-item pleasure scale covers four domains of pleasure response: interest/pastimes, social interaction, sensory experience and food/drink.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

recent use of inhaled (i.e., snorted), smoked or injected methamphetamine

Exclusion Criteria:

Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant.
Current or past histories of substance use 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 methamphetamine, methylphenidate, or duloxetine.