Pioglitazone for Heroin and for Nicotine Dependence

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01395797
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH), Omeros Corporation (Industry)
• Enrollment: 82
• Location: 1
• Arms: 6
• Duration (Months): 39
• Patients Per Site Per Month: 2.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heroin Dependence; Nicotine Dependence	Drug: PIO; Drug: Placebo	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Effects of Pioglitazone, a PPARγ Agonist, on the Abuse Liability of Heroin and of Nicotine
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute on Drug Abuse (NIDA)
• Omeros Corporation

Investigators

• Principal Investigator: Sandra D. Comer, MD, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01395797
• Other Study ID Numbers: 6255; R01DA031022
• First Posted: Jul 18, 2011
• Last Update Posted: Jul 13, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Tobacco Use Disorder; Heroin Dependence; Pioglitazone

Study Results

Participant Flow

Arm/Group Title	Placebo - Heroin	Pio Low Dose - Heroin	Pio High Dose - Heroin	Placebo - Nicotine	Pio Low Dose - Nicotine	Pio High Dose - Nicotine
Arm/Group Description	Control condition for active arms. Placebo: Placebo - Heroin	Low dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.	High dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.	Control condition for active arms. Pioglitazone: 0, 15, and 45 mg per day.	Low dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.	High dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.
Period Title: Overall Study
STARTED	19	4	18	15	9	17
COMPLETED	16	3	14	13	7	14
NOT COMPLETED	3	1	4	2	2	3

Baseline Characteristics

Arm/Group Title	Placebo - Heroin	Pio Low Dose - Heroin	Pio High Dose - Heroin	Placebo - Nicotine	Pio Low Dose - Nicotine	Pio High Dose - Nicotine	Total
Arm/Group Description	Control condition for active arms. Placebo: Placebo - Heroin	Low dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.	High dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.	Control condition for active arms. Pioglitazone: 0, 15, and 45 mg per day.	Low dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.	High dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.	Total of all reporting groups
Overall Participants	19	4	18	15	9	17	82
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	19 100%	4 100%	18 100%	15 100%	9 100%	17 100%	82 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	2 11.1%	2 13.3%	1 11.1%	2 11.8%	7 8.5%
Male	19 100%	4 100%	16 88.9%	13 86.7%	8 88.9%	15 88.2%	75 91.5%
Region of Enrollment (participants) [Number]
United States	19 100%	4 100%	18 100%	15 100%	9 100%	17 100%	82 100%

Outcome Measures

1. Primary Outcome

Title	Drug's Break Point
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo - Heroin	Pio Low Dose- Heroin	Pio High Dose - Heroin	Placebo - Nicotine	Pio Low Dose- Nicotine	Pio High Dose - Nicotine
Arm/Group Description	Control condition for active arms. Placebo: Placebo - Heroin	Low dose of Pio comparator	High dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.	Control condition for active arms. Pioglitazone: 0, 15, and 45 mg per day.	Low dose Pio comparator.	High dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.
Measure Participants	16	3	14	13	7	14
Mean (Standard Deviation) [Mouse clicks]	1037 (1763)	1200 (272)	2014 (2835)	568 (652)	722 (823)	960 (1004)

2. Secondary Outcome

Title	Measures of Subjective Drug Effects Most Commonly Indicative of Abuse Liability.
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo - Heroin	Pio Low Dose- Heroin	Pio High Dose - Heroin	Placebo - Nicotine	Pio Low Dose- Nicotine	Pio High Dose - Nicotine
Arm/Group Description	Participants will be maintained on 0 mg of PIO prior to sessions assessing the abuse liability of heroin. Placebo: Placebo	Participants will be maintained on 15 mg of PIO prior to assessing the abuse liability of heroin.	Participants will be maintained on 45 mg of PIO prior to sessions assessing the abuse liability of heroin.	Participants will be maintained on 0 mg of PIO prior to sessions assessing the abuse liability of nicotine.	Participants will be maintained on 15 mg of PIO prior to assessing the abuse liability of nicotine.	Participants will be maintained on 45 mg of PIO prior to sessions assessing the abuse liability of nicotine
Measure Participants	16	3	14	13	7	14
Mean (Standard Error) [units on a scale]	24 (13)	15 (9)	19 (6)	59 (9)	68 (12)	62.5 (10)

Adverse Events

Arm/Group Title	Placebo - Heroin		Pio Low Dose - Heroin		Pio High Dose - Heroin		Placebo - Nicotine		Pio Low Dose - Nicotine		Pio High Dose - Nicotine
Arm/Group Description	Control condition for active arms. Placebo: Placebo - Heroin		Low dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.		High dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.		Control condition for active arms. Pioglitazone: 0, 15, and 45 mg per day.		Low dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.		High dose pio comparator. Pioglitazone: 0, 15, and 45 mg per day.
All Cause Mortality
	Placebo - Heroin		Pio Low Dose - Heroin		Pio High Dose - Heroin		Placebo - Nicotine		Pio Low Dose - Nicotine		Pio High Dose - Nicotine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo - Heroin		Pio Low Dose - Heroin		Pio High Dose - Heroin		Placebo - Nicotine		Pio Low Dose - Nicotine		Pio High Dose - Nicotine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/4 (0%)		0/18 (0%)		0/15 (0%)		0/9 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Placebo - Heroin		Pio Low Dose - Heroin		Pio High Dose - Heroin		Placebo - Nicotine		Pio Low Dose - Nicotine		Pio High Dose - Nicotine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/4 (0%)		0/18 (0%)		0/15 (0%)		0/9 (0%)		0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.