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

Study Overview
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Brief Summary
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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.

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

Conditions
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Methamphetamine Use Disorder

Intervention / Treatment
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* Drug: Methamphetamine
* Drug: Methylphenidate
* Drug: Placebo oral capsule
* Drug: Duloxetine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Comparator: Placebo<br>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<br>* In each arm, subjects will receive doses of methamphetamine.<br>* Other names: Metamfetamine;Drug: Methylphenidate<br>* In each arm, subjects will receive methylphenidate capsules.<br>* Other names: Metadate®;Drug: Placebo oral capsule<br>* In each arm, subjects will receive placebo capsules.<br>* Other names: Lactose;|
| Active Comparator: Active Comparator: Duloxetine<br>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<br>* In each arm, subjects will receive doses of methamphetamine.<br>* Other names: Metamfetamine;Drug: Methylphenidate<br>* In each arm, subjects will receive methylphenidate capsules.<br>* Other names: Metadate®;Drug: Placebo oral capsule<br>* In each arm, subjects will receive placebo capsules.<br>* Other names: Lactose;Drug: Duloxetine<br>* Subjects will receive duloxetine capsules in the duloxetine arm.<br>* Other names: Cymbalta®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate After Methamphetamine Administration Following Methylphenidate (0 mg) Maintenance. | Heart Rate (beats per minute) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Heart Rate After Methamphetamine Administration Following Methylphenidate (20 mg) Maintenance. | Heart Rate (beats per minute) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Heart Rate After Methamphetamine Administration Following Methylphenidate (40 mg) Maintenance. | Heart Rate (beats per minute) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Heart Rate After Methamphetamine Administration Following Methylphenidate (60 mg) Maintenance. | Heart Rate (beats per minute) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Systolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (0 mg) Maintenance. | Systolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Systolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (20 mg) Maintenance. | Systolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Systolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (40 mg) Maintenance. | Systolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Systolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (60 mg) Maintenance. | Systolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Diastolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (0 mg) Maintenance. | Diastolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Diastolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (20 mg) Maintenance. | Diastolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Diastolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (40 mg) Maintenance. | Diastolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Diastolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (60 mg) Maintenance. | Diastolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Temperature After Methamphetamine Administration Following Methylphenidate (0 mg) Maintenance. | Oral temperature (degrees fahrenheit) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Temperature After Methamphetamine Administration Following Methylphenidate (20 mg) Maintenance. | Oral temperature (degrees fahrenheit) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Temperature After Methamphetamine Administration Following Methylphenidate (40 mg) Maintenance. | Oral temperature (degrees fahrenheit) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Temperature After Methamphetamine Administration Following Methylphenidate (60 mg) Maintenance. | Oral temperature (degrees fahrenheit) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg) | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (0 mg) Administration Following Methylphenidate (0 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (10 mg) Administration Following Methylphenidate (0 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (20 mg) Administration Following Methylphenidate (0 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (0 mg) Administration Following Methylphenidate (20 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (10 mg) Administration Following Methylphenidate (20 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (20 mg) Administration Following Methylphenidate (20 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (0 mg) Administration Following Methylphenidate (40 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (10 mg) Administration Following Methylphenidate (40 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (20 mg) Administration Following Methylphenidate (40 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (0 mg) Administration Following Methylphenidate (60 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (10 mg) Administration Following Methylphenidate (60 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 
| Subjective Effects of Methamphetamine (20 mg) Administration Following Methylphenidate (60 mg) Maintenance. | Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine. | Daily over approximately 1 week of inpatient stay. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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