Effects of Pioglitazone, a PPARgamma Receptor Agonist, on the Abuse Liability of Oxycodone

Study Overview
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Brief Summary
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The ability of pioglitazone (PIO) to alter the effects of opioids in humans has not been characterized in a controlled laboratory setting. Accordingly, the proposed investigation seeks to examine the effects of PIO on oxycodone, one of the most commonly used and abused opioid drugs in the U.S. (Davis et al., 2003). More specifically, the primary aim of this investigation is to characterize the subjective effects of oxycodone under maintenance on various doses of PIO (0, 15, and 45 mg) in non-dependent, prescription opioid abusers. Secondary aims of the study are to examine the influence of PIO on the analgesic, cognitive, and physiological effects of oxycodone.

Detailed Description
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This 9-week investigation will use an inpatient/outpatient design in which participants will be maintained on ascending doses of pioglitazone (3 weeks on placebo followed by 3 weeks on PIO 15 mg followed by 3 weeks on PIO 45 mg). At the end of each maintenance period the effects of oxycodone (0, 10, and 20 mg) will be examined during a single laboratory session using a cumulative dosing procedure.

Official Title
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Effects of Pioglitazone, a PPARgamma Receptor Agonist, on the Abuse Liability of Oxycodone

Conditions
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Opioid Abuse

Intervention / Treatment
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* Drug: pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recreational use of prescription opioids at least once per month within the past year No current major mood, psychotic, or anxiety disorder Physically healthy aspartate aminotransferase (AST) or alanine aminotransferase (ALT) within normal limits Able to perform study procedures 6.21-45 years of age 7.Blood glucose concentration between 70-145 mg/dl for men and 70-125 mg/dl for women (fasting) 8.Hb > 13 for men and Hb > 11 for women with no other evidence of medical disorder resulting in blood loss or anemia/hematological disease Exclusion Criteria: Physical dependence on any drugs, excluding nicotine and caffeine Participants requesting treatment Participants on parole or probation Pregnancy or lactation: Female participants must agree to the use of a barrier control method of contraception (e.g. male and female condoms, diaphragms, cervical caps and contraceptive sponges used in combination with spermicide) Current or recent history of significant violent behavior (within the past 6 months) Current major Axis I psychopathology that might interfere with ability to participate in the study Significant suicide risk Current chronic pain Current or history of congestive heart failure, edema, or diabetes mellitus Sensitivity, allergy, or contraindication to opioids or pioglitazone Unstable physical disorders that might make participation hazardous, such as end-stage AIDS, hypertension (blood pressure > 140/90), or heart disease (please note that participants will be asked about previous visits to a cardiologist, chest pain, or strong palpitations; if these exist, they will be referred to a cardiologist and excluded unless cleared for participation by a cardiologist)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 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: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Maintenance Period<br>Participants will complete the various outcome measures following a 2-3 week maintenance period on Placebo (PCB). | Drug: pioglitazone<br>* A PPARγ agonist, also marketed as Actos. Participants will be maintained on ascending doses of Placebo, pioglitazone 15 mg and 45 mg, prior to completing a lab session at the end of each dosing period.<br>* Other names: Actos;|
| Experimental: PIO 15 Maintenance Period<br>Participants will complete the various outcome measures following a 2-3 week maintenance period on Pioglitazone (PIO) 15 mg. | Drug: pioglitazone<br>* A PPARγ agonist, also marketed as Actos. Participants will be maintained on ascending doses of Placebo, pioglitazone 15 mg and 45 mg, prior to completing a lab session at the end of each dosing period.<br>* Other names: Actos;|
| Experimental: PIO 45 Maintenance Period<br>Participants will complete the various outcome measures following a 2-3 week maintenance period on Pioglitazone (PIO) 45 mg. | Drug: pioglitazone<br>* A PPARγ agonist, also marketed as Actos. Participants will be maintained on ascending doses of Placebo, pioglitazone 15 mg and 45 mg, prior to completing a lab session at the end of each dosing period.<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Ratings of Good Drug Effect | Visual analog scale ratings (0-100 mm scale, 0=Not at all, 100=Extremely) | Measured during the lab session conducted at the end of each maintenance period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analgesic Responses Using the Cold Pressor Test | Latency to withdraw hand from cold water during the cold pressor test. | Measured during the lab session conducted at the end of each maintenance period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oxycodone, Opioid abuse