Pioglitazone for Heroin and for Nicotine Dependence

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

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.

Study Overview

• Status: Terminated
• Conditions: Heroin Dependence; Nicotine Dependence
• Intervention / Treatment: Drug: Placebo; Drug: PIO

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.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute on Drug Abuse (NIDA); Omeros Corporation
• Investigators: Principal Investigator: Sandra D. Comer, MD, Columbia University

Publications and helpful links

General Publications

• Martinez S, Jones JD, Vadhan NP, Brandt L, Comer SD, Bisaga A. The acute and repeated effects of cigarette smoking and smoking-related cues on impulsivity. Drug Alcohol Rev. 2021 Jul;40(5):864-868. doi: 10.1111/dar.13206. Epub 2020 Nov 2.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: July 13, 2011
• First Submitted That Met QC Criteria: July 14, 2011
• First Posted (Estimate): July 18, 2011

Study Record Updates

• Last Update Posted (Actual): July 13, 2017
• Last Update Submitted That Met QC Criteria: July 11, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Tobacco Use Disorder; Heroin Dependence; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: 6255; R01DA031022 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data will be presented at conferences and published in a peer-reviewed journal.