Heroin Dependence, Nicotine Dependence
Conditions
Brief summary
The goal of the proposed research is to improve the effectiveness of treatments for opioid and for nicotine dependence by testing a novel pharmacological strategy. Specifically, pioglitazone, a peroxisome proliferator-activated gamma receptor (PPARγ) agonist, will be used as an adjunct to agonist-based treatment.
Detailed description
Although treatments for opioid and for nicotine dependence exist, these medications are not universally effective as many patients are unable to stop using or relapse rapidly, suggesting that treatment with a single agent alone is insufficient to facilitate cessation of use in many patients. Targeting additional pathways that may contribute to the maintenance of drug-taking behaviors or relapse may be a more effective strategy to treat individuals resistant to first-line approaches.
Interventions
DRUGPIO
0, 15, and 45 mg per day.
DRUGPlacebo
Placebo
Sponsors
National Institute on Drug Abuse (NIDA)
Omeros Corporation
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 21-55 years of age * Physically healthy * Able to perform study procedures
Exclusion criteria
* Pregnancy * Physical dependence on any other drugs besides caffeine, heroin and nicotine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug's Break Point | Following 2 weeks of Pioglitazone (PIO) maintenance. | Number of operant responses (mouse clicks) participants were willing to provide in order to receive the drug under investigation (heroin or nicotine). The Breakpoint is the point at which participants stopped responding for the drug, i.e., the total number of clicks they were willing to provide in order to receive the drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measures of Subjective Drug Effects Most Commonly Indicative of Abuse Liability. | Following 2 weeks of Pioglitazone (PIO) maintenance. | Visual analog scale ratings of Liking reported by the participant will be the primary endpoint (0-100 mm, 0=Not at all, 100=Extremely). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo - Heroin Control condition for active arms.
Placebo: Placebo - Heroin | 19 |
| Pio Low Dose - Heroin Low dose pio comparator.
Pioglitazone: 0, 15, and 45 mg per day. | 4 |
| Pio High Dose - Heroin High dose pio comparator.
Pioglitazone: 0, 15, and 45 mg per day. | 18 |
| Placebo - Nicotine Control condition for active arms.
Pioglitazone: 0, 15, and 45 mg per day. | 15 |
| Pio Low Dose - Nicotine Low dose pio comparator.
Pioglitazone: 0, 15, and 45 mg per day. | 9 |
| Pio High Dose - Nicotine High dose pio comparator.
Pioglitazone: 0, 15, and 45 mg per day. | 17 |
| Total | 82 |
Baseline characteristics
| Characteristic | Placebo - Heroin | Pio Low Dose - Heroin | Pio High Dose - Heroin | Placebo - Nicotine | Pio Low Dose - Nicotine | Pio High Dose - Nicotine | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 4 Participants | 18 Participants | 15 Participants | 9 Participants | 17 Participants | 82 Participants |
| Region of Enrollment United States | 19 participants | 4 participants | 18 participants | 15 participants | 9 participants | 17 participants | 82 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 19 Participants | 4 Participants | 16 Participants | 13 Participants | 8 Participants | 15 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 19 | 0 / 4 | 0 / 18 | 0 / 15 | 0 / 9 | 0 / 17 |
| serious Total, serious adverse events | 0 / 19 | 0 / 4 | 0 / 18 | 0 / 15 | 0 / 9 | 0 / 17 |
Outcome results
Primary
Drug's Break Point
Number of operant responses (mouse clicks) participants were willing to provide in order to receive the drug under investigation (heroin or nicotine). The Breakpoint is the point at which participants stopped responding for the drug, i.e., the total number of clicks they were willing to provide in order to receive the drug.
Time frame: Following 2 weeks of Pioglitazone (PIO) maintenance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Heroin | Drug's Break Point | 1037 Mouse clicks | Standard Deviation 1763 |
| Pio Low Dose- Heroin | Drug's Break Point | 1200 Mouse clicks | Standard Deviation 272 |
| Pio High Dose - Heroin | Drug's Break Point | 2014 Mouse clicks | Standard Deviation 2835 |
| Placebo - Nicotine | Drug's Break Point | 568 Mouse clicks | Standard Deviation 652 |
| Pio Low Dose- Nicotine | Drug's Break Point | 722 Mouse clicks | Standard Deviation 823 |
| Pio High Dose - Nicotine | Drug's Break Point | 960 Mouse clicks | Standard Deviation 1004 |
Secondary
Measures of Subjective Drug Effects Most Commonly Indicative of Abuse Liability.
Visual analog scale ratings of Liking reported by the participant will be the primary endpoint (0-100 mm, 0=Not at all, 100=Extremely).
Time frame: Following 2 weeks of Pioglitazone (PIO) maintenance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Heroin | Measures of Subjective Drug Effects Most Commonly Indicative of Abuse Liability. | 24 units on a scale | Standard Error 13 |
| Pio Low Dose- Heroin | Measures of Subjective Drug Effects Most Commonly Indicative of Abuse Liability. | 15 units on a scale | Standard Error 9 |
| Pio High Dose - Heroin | Measures of Subjective Drug Effects Most Commonly Indicative of Abuse Liability. | 19 units on a scale | Standard Error 6 |
| Placebo - Nicotine | Measures of Subjective Drug Effects Most Commonly Indicative of Abuse Liability. | 59 units on a scale | Standard Error 9 |
| Pio Low Dose- Nicotine | Measures of Subjective Drug Effects Most Commonly Indicative of Abuse Liability. | 68 units on a scale | Standard Error 12 |
| Pio High Dose - Nicotine | Measures of Subjective Drug Effects Most Commonly Indicative of Abuse Liability. | 62.5 units on a scale | Standard Error 10 |