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

NCT04178993 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: BED(IN):40R01DA047391
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

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.

Conditions

Methamphetamine Use Disorder

Keywords

Methamphetamine; Methylphenidate; Duloxetine Hydrochloride; Central Nervous System Stimulants; Physiological Effects of Drugs; Dopamine Uptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Membrane Transport Modulators; Neurotransmitter Agents; Dopamine Agents; Molecular Mechanisms of Pharmacological Action; Sensory System Agents; Peripheral Nervous System Agents; Vasoconstrictor Agents; Antidepressive Agents; Psychotropic Drugs

Outcome Measures

Primary Outcomes (4)

• Reinforcing Effects of Methamphetamine Following Methylphenidate (0 mg; Placebo) Maintenance.

  Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement. Subjects sample a dose of methamphetamine (0, 10, or 20 mg) and then have ten opportunities (e.g., trials) to "work" for a 1/10th of the sampled dose via clicking on a computer mouse (i.e., 10 completed trials is the full sampled dose).

  Following at least 4 days of maintenance on placebo during inpatient admission, up to 1 week

• Reinforcing Effects of Methamphetamine Following Methylphenidate (20 mg) Maintenance.

  Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement. Subjects sample a dose of methamphetamine (0, 10, or 20 mg) and then have the ten opportunities (e.g., trials) to "work" for a 1/10th of the sampled dose via clicking on a computer mouse (i.e., 10 completed trials is the full sampled dose).

  Following at least 4 days of maintenance on drug during inpatient admission, up to 1 week

• Reinforcing Effects of Methamphetamine Following Methylphenidate (40 mg) Maintenance.

  Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement. Subjects sample a dose of methamphetamine (0, 10, or 20 mg) and then have the ten opportunities (e.g., trials) to "work" for a 1/10th of the sampled dose via clicking on a computer mouse (i.e., 10 completed trials is the full sampled dose).

  Following at least 4 days of maintenance on drug during inpatient admission, up to 1 week

• Reinforcing Effects of Methamphetamine Following Methylphenidate (60 mg) Maintenance.

  Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement. Subjects sample a dose of methamphetamine (0, 10, or 20 mg) and then have the ten opportunities (e.g., trials) to "work" for a 1/10th of the sampled dose via clicking on a computer mouse (i.e., 10 completed trials is the full sampled dose).

  Following at least 4 days of maintenance on drug during inpatient admission, up to 1 week

Secondary Outcomes (28)

• Heart Rate After Methamphetamine Administration Following Methylphenidate (0 mg) Maintenance.

  Daily over approximately 1 week of inpatient stay.

• Heart Rate After Methamphetamine Administration Following Methylphenidate (20 mg) Maintenance.

  Daily over approximately 1 week of inpatient stay.

• Heart Rate After Methamphetamine Administration Following Methylphenidate (40 mg) Maintenance.

  Daily over approximately 1 week of inpatient stay.

• Heart Rate After Methamphetamine Administration Following Methylphenidate (60 mg) Maintenance.

  Daily over approximately 1 week of inpatient stay.

• Systolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (0 mg) Maintenance.

  Daily over approximately 1 week of inpatient stay.

Other Outcomes (4)

• Attentional Bias

  12 sessions over approximately 4.5 weeks

• Snaith-Hamilton-Pleasure Scale to Measure Anhedonia (Inability to Experience Pleasure)

  4 times over approximately 4.5 weeks

• Delay Discounting for Methamphetamine

  4 sessions over approximately 4.5 weeks

Study Arms (2)

Placebo Comparator: Placebo

PLACEBO COMPARATOR

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; Drug: Methylphenidate; Drug: Placebo oral capsule

Active Comparator: Duloxetine

ACTIVE COMPARATOR

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; Drug: Methylphenidate; Drug: Placebo oral capsule; Drug: Duloxetine

Interventions

Methamphetamine DRUG

In each arm, subjects will receive doses of methamphetamine.

Also known as: Metamfetamine

Active Comparator: Duloxetine; Placebo Comparator: Placebo

Methylphenidate DRUG

In each arm, subjects will receive methylphenidate capsules.

Also known as: Metadate®

Active Comparator: Duloxetine; Placebo Comparator: Placebo

Placebo oral capsule DRUG

In each arm, subjects will receive placebo capsules.

Also known as: Lactose

Active Comparator: Duloxetine; Placebo Comparator: Placebo

Duloxetine DRUG

Subjects will receive duloxetine capsules in the duloxetine arm.

Also known as: Cymbalta®

Active Comparator: Duloxetine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Craig Rush: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

University of Kentucky

Lexington, Kentucky, 40507, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Interventions

Methamphetamine; Methylphenidate; Lactose; Duloxetine Hydrochloride

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars; Thiophenes; Sulfur Compounds

Results Point of Contact

• Title: Dr. Craig Rush, Ph.D.
• Organization: University of Kentucky

crush2@uky.edu

8592575388

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: November 26, 2019
• Study Start: September 1, 2019
• Primary Completion: May 5, 2021
• Study Completion: May 5, 2021
• Last Updated: January 9, 2023
• Results First Posted: January 9, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)