Pioglitazone for Heroin and for Nicotine Dependence

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Pioglitazone, a PPARγ Agonist, on the Abuse Liability of Heroin and of Nicotine

Conditions
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Heroin Dependence, Nicotine Dependence

Intervention / Treatment
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* Drug: PIO
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo - Heroin<br>Participants will be maintained on 0 mg of Pioglitazone (PIO) prior to sessions assessing the abuse liability of heroin. | Drug: Placebo<br>* Placebo<br>* Other names: Actos;|
| Experimental: PIO low dose - Heroin<br>Participants will be maintained on 15 mg of PIO prior to sessions assessing the abuse liability of heroin. | Drug: PIO<br>* 0, 15, and 45 mg per day.<br>* Other names: Actos;|
| Experimental: PIO high dose - Heroin<br>Participants will be maintained on 45 mg of PIO prior to sessions assessing the abuse liability of heroin. | Drug: PIO<br>* 0, 15, and 45 mg per day.<br>* Other names: Actos;|
| Placebo Comparator: Placebo - Nicotine<br>Participants will be maintained on 0 mg of PIO prior to sessions assessing the abuse liability of nicotine. | Drug: PIO<br>* 0, 15, and 45 mg per day.<br>* Other names: Actos;|
| Experimental: PIO Low Dose - Nicotine<br>Participants will be maintained on 15 mg of PIO prior to sessions assessing the abuse liability of nicotine | Drug: PIO<br>* 0, 15, and 45 mg per day.<br>* Other names: Actos;|
| Experimental: PIO High Dose - Nicotine<br>Participants will be maintained on 45 mg of PIO prior to sessions assessing the abuse liability of nicotine | Drug: PIO<br>* 0, 15, and 45 mg per day.<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Following 2 weeks of Pioglitazone (PIO) maintenance. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Following 2 weeks of Pioglitazone (PIO) maintenance. |