Opioid Abuse
Conditions
Keywords
Oxycodone, Opioid abuse
Brief summary
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
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.
Interventions
DRUGpioglitazone
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.
Sponsors
Omeros Corporation
New York State Psychiatric Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Recreational use of prescription opioids at least once per month within the past year 2. No current major mood, psychotic, or anxiety disorder 3. Physically healthy 4. aspartate aminotransferase (AST) or alanine aminotransferase (ALT) within normal limits 5. 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
1. Physical dependence on any drugs, excluding nicotine and caffeine 2. Participants requesting treatment 3. Participants on parole or probation 4. 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) 5. Current or recent history of significant violent behavior (within the past 6 months) 6. Current major Axis I psychopathology that might interfere with ability to participate in the study 7. Significant suicide risk 8. Current chronic pain 9. Current or history of congestive heart failure, edema, or diabetes mellitus 10. Sensitivity, allergy, or contraindication to opioids or pioglitazone 11. 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Ratings of Good Drug Effect | Measured during the lab session conducted at the end of each maintenance period | Visual analog scale ratings (0-100 mm scale, 0=Not at all, 100=Extremely) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analgesic Responses Using the Cold Pressor Test | Measured during the lab session conducted at the end of each maintenance period | Latency to withdraw hand from cold water during the cold pressor test. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Withing-subjects, Placebo-Controlled Participants will complete the various outcome measures following maintenance period of: Placebo, Pioglitazone 15 mg, and 45 mg. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Physician Decision | 5 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Withing-subjects, Placebo-Controlled |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 35 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
Primary
Subjective Ratings of Good Drug Effect
Visual analog scale ratings (0-100 mm scale, 0=Not at all, 100=Extremely)
Time frame: Measured during the lab session conducted at the end of each maintenance period
Population: Shown below are peak drug effects from each of the 3 maintenance periods (Placebo, Pioglitazone (PIO) 15, and PIO 45)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Subjective Ratings of Good Drug Effect | Placebo | 37 units on a scale | Standard Deviation 12 |
| All Participants | Subjective Ratings of Good Drug Effect | PIO 15 | 35 units on a scale | Standard Deviation 9 |
| All Participants | Subjective Ratings of Good Drug Effect | PIO 45 | 35 units on a scale | Standard Deviation 11 |
Secondary
Analgesic Responses Using the Cold Pressor Test
Latency to withdraw hand from cold water during the cold pressor test.
Time frame: Measured during the lab session conducted at the end of each maintenance period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Analgesic Responses Using the Cold Pressor Test | Placebo | 110 seconds | Standard Deviation 23 |
| All Participants | Analgesic Responses Using the Cold Pressor Test | PIO 15 | 71 seconds | Standard Deviation 8 |
| All Participants | Analgesic Responses Using the Cold Pressor Test | PIO 45 | 75 seconds | Standard Deviation 10 |