Pioglitazone as an Adjunct to Cognitive-Behavioral Therapy for Cocaine Relapse Prevention

NCT ID: NCT04843046

Last Updated: 2025-09-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-23

Study Completion Date

2026-02-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to see how well pioglitazone, when used with cognitive behavioral therapy, works at helping people who have recently stopped using cocaine to continue to not use cocaine.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Over one million American adults suffer from cocaine use disorder (CUD) with recent trends showing an increase in cocaine-related deaths since 2010. For the chronic cocaine user, significant changes in brain function and structure set the stage for relapse that, unfortunately, continues to be the most common outcome following treatment. For substance use disorders, cognitive-behavioral therapy (CBT) is arguably the most empirically supported and widely used relapse prevention approach. Considered to be a cognitive control therapy, CBT aims to improve 'top-down' executive control functions that are impaired in CUD and strongly connected to relapse. Converging evidence suggests that CBT promotes meaningful changes in brain regions associated with cognitive control. Still, many patients with cognitive impairments show suboptimal response to CBT, bolstering the call for research aimed at improving effects with integrative treatments.

The goal of this project is to enhance the relapse-prevention effects of CBT with adjunctive use of pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist. Unlike traditional medications that target classic neurotransmitter systems, PIO's activation of the PPAR pathway confers broad spectrum anti-inflammatory and neuroprotective effects against insult to brain white matter (WM). The functional significance of WM in CUD has been well established by evidence showing that: (1) chronic cocaine exposure alters WM structural integrity; (2) WM alterations compromise cognitive function in CUD; and (2) better WM integrity predicts better CUD treatment outcome. In a recent proof of concept trial it was found that PIO significantly improved brain WM integrity in a small sample of non-abstinent patients with CUD. Treatment with PIO was well-tolerated and associated with reduced cocaine craving relative to placebo. Collectively, these findings raise the exciting possibility that PIO may augment responding to CBT via improved neural structure and cognitive function.

A randomized double-blind clinical trial will be utilized to evaluate the efficacy of CBT with adjunctive PIO in recently abstinent patients during the early phase of recovery when craving is prominent, relapse risk is high, and intact cognitive control is required to actively maintain abstinence. Upon completion of a 5-day inpatient detoxification, 60 adults with CUD will complete titration to full dose of randomized medication, either PIO (45mg daily) or placebo, and begin 12 weeks of outpatient CBT treatment while continuing to receive study medication. Specific aims will examine the effects of PIO on targeted mechanisms of change (WM integrity, cognitive function, cocaine craving) and demonstrate evidence linking clinical efficacy (abstinence, functional health) with mechanism engagement. Expected results will establish PIO as an adjunctive treatment that can be integrated with CBT to reduce relapse risk following detoxification, thereby meeting NIDA's strategic priority of evaluating the use of medications to improve the efficacy of behavioral interventions (PA-18-055).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cocaine Use Disorder

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

CBT + pioglitazone

Cognitive Behavioral Therapy will be administered twice weekly during weeks 1-4 and once weekly during weeks 5-12 and augmented with a pioglitazone (45 mg) capsule every day during weeks 1-12.

Group Type ACTIVE_COMPARATOR

Cognitive Behavioral Therapy (CBT)

Intervention Type BEHAVIORAL

All participants will receive evidence-based individual Cognitive Behavioral Therapy (CBT) shown to be an effective intervention for maintaining abstinence following detoxification. Trained masters-level licensed professional counselors will deliver CBT.

Pioglitazone

Intervention Type DRUG

Pioglitazone capsules will start at 30 mg (Detox days 3 and 4) and increase to fixed dose of 45 mg for study weeks 1-12 and will also contain riboflavin.

CBT + placebo

Cognitive Behavioral Therapy will be administered twice weekly during weeks 1-4 and once weekly during weeks 5-12 and augmented with a placebo capsule every day during weeks 1-12.

Group Type PLACEBO_COMPARATOR

Cognitive Behavioral Therapy (CBT)

Intervention Type BEHAVIORAL

All participants will receive evidence-based individual Cognitive Behavioral Therapy (CBT) shown to be an effective intervention for maintaining abstinence following detoxification. Trained masters-level licensed professional counselors will deliver CBT.

Placebo

Intervention Type DRUG

Placebo capsules will be filled with corn starch and riboflavin.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Cognitive Behavioral Therapy (CBT)

All participants will receive evidence-based individual Cognitive Behavioral Therapy (CBT) shown to be an effective intervention for maintaining abstinence following detoxification. Trained masters-level licensed professional counselors will deliver CBT.

Intervention Type BEHAVIORAL

Pioglitazone

Pioglitazone capsules will start at 30 mg (Detox days 3 and 4) and increase to fixed dose of 45 mg for study weeks 1-12 and will also contain riboflavin.

Intervention Type DRUG

Placebo

Placebo capsules will be filled with corn starch and riboflavin.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

CBT Actos Corn Starch

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 18 to 65 years old
* meet DSM 5 diagnostic criteria for cocaine use disorder
* report recent cocaine use, verified by at least one positive urine drug screen for the cocaine metabolite, benzoylecgonine, during intake
* be judged by the medical staff to be psychiatrically stable and physically healthy
* for females, be using an effective form of birth control (e.g., barrier, IUD, or sterilization) and not be pregnant as determined by a serum pregnancy test at screening and negative urine pregnancy test at intake prior to first dose of investigational drug (test will be repeated weekly to ensure that female patients do not continue in the study if pregnant) or lactating
* be willing to be admitted to a 5-day inpatient detoxification program at The Right Step Houston
* be able to understand the consent form and provide written informed consent
* be able to provide the names of at least 2 persons who can consistently locate their whereabouts

Exclusion Criteria

* have an acute medical or psychiatric disorder that would, in the judgment of the study physician, make participation difficult or unsafe
* have suicidal or homicidal ideation that requires immediate attention
* have another current (≥ moderate) substance use disorder aside from alcohol, nicotine, or marijuana
* have a medical condition contraindicating PIO pharmacotherapy (e.g., drug- or insulin-dependent diabetes, congestive heart failure, edema, clinical significant liver disease, hypoglycemia, history of bladder cancer) or be taking medications that would adversely interact with PIO (e.g., CYP2C8 inhibitors or inducers, antihyperglycemic medications)
* be concurrently enrolled in other addiction treatment services aside from smoking cessation
* if female, be currently pregnant, breastfeeding, or planning on conception
* have conditions of probation or parole requiring reports of drug use to officers of the court
* be unable to read, write, or speak English
* be homeless (live on the street)
* have medical contraindications to MRI/DTI scans (e.g., history of pacemaker, metal implants, or welding/metal work without protective eyewear)
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Joy Schmitz

Professor, Faillace Chair, and Director for the Center for Neurobehavioral Research on Addiction

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Joy M Schmitz, PhD

Role: PRINCIPAL_INVESTIGATOR

UT Houston

Scott D Lane, PhD

Role: PRINCIPAL_INVESTIGATOR

UT Houston

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

UTHealth Center for Neurobehavioral Research on Addiction

Houston, Texas, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Joy M Schmitz, PhD

Role: CONTACT

713-486-2867

Jessica N Vincent, BS

Role: CONTACT

713-486-2803

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Joy M Schmitz, PhD

Role: primary

713-486-2867

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R01DA048026

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC-MS-19-0718

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Cocaine and Pentoxifylline (BED IN 47)
NCT07086794 RECRUITING EARLY_PHASE1
Exenatide for Treating Cocaine Use Disorder
NCT04941521 COMPLETED PHASE1/PHASE2