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

NCT04843046 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: HSC-MS-19-0718R01DA048026
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cocaine Use Disorder

Keywords

Cocaine Use; Cocaine Addiction; Cognitive Behavioral Therapy; Relapse Prevention

Outcome Measures

Primary Outcomes (14)

• Change in white matter integrity as assessed by change in fractional anisotropy value measured by diffusion tensor imaging

  Anisotropy values range from 0 to 1, where a higher value indicates greater white matter integrity.

  Week 0 and Week 12

• Change in white matter integrity as assessed by change in radial diffusivity value measured by diffusion tensor imaging

  Radial diffusivity (RD) values are not bound by specified upper and lower ranges, as the metric is a derivation of two diffusion eigenvalues = (\[lambda2 / lambda3\] / 2). Higher RD values are indicative of decreased white matter integrity as related to myelin integrity; conversely lower RD scores indicate better white matter integrity.

  Week 0 and Week 12

• Change in working memory as assessed by the NIH Toolbox Cognition Battery List Sorting Task

  The List Sorting Task has an age-adjusted scale score that ranges from 0 to 100, with a higher score indicating better performance.

  Week 0

• Change in working memory as assessed by the NIH Toolbox Cognition Battery List Sorting Task

  The List Sorting Task has an age-adjusted scale score that ranges from 0 to 100, with a higher score indicating better performance.

  Week 4

• Change in working memory as assessed by the NIH Toolbox Cognition Battery List Sorting Task

  The List Sorting Task has an age-adjusted scale score that ranges from 0 to 100, with a higher score indicating better performance.

  Week 12

• Change in attention/impulsivity as assessed by the NIH Toolbox Cognition Battery Flanker Test

  The Flanker Test has an age-adjusted scale score that ranges from 0 to 100, with a higher score indicating better performance.

  Week 0

• Change in attention/impulsivity as assessed by the NIH Toolbox Cognition Battery Flanker Test

  The Flanker Test has an age-adjusted scale score that ranges from 0 to 100, with a higher score indicating better performance.

  Week 4

• Change in attention/impulsivity as assessed by the NIH Toolbox Cognition Battery Flanker Test

  The Flanker Test has an age-adjusted scale score that ranges from 0 to 100, with a higher score indicating better performance.

  Week 12

• Change in cognitive function as assessed by the NIH Toolbox Cognition Battery Fluid Cognition Composite score

  The Fluid Cognition Composite score is the normed standardized score ranging from 0 to 145, with a higher score indicating better performance.

  Week 0

• Change in cognitive function as assessed by the NIH Toolbox Cognition Battery Fluid Cognition Composite score

  The Fluid Cognition Composite score is the normed standardized score ranging from 0 to 145, with a higher score indicating better performance.

  Week 4

• Change in cognitive function as assessed by the NIH Toolbox Cognition Battery Fluid Cognition Composite score

  The Fluid Cognition Composite score is the normed standardized score ranging from 0 to 145, with a higher score indicating better performance.

  Week 12

• Number of participants who don't relapse as assessed by continuous cocaine-negative urine drug screens in the final three weeks of treatment

  For a cocaine-negative urine drug screen result, benzoylecgonine levels must be under 150 ng/mL.

  From Week 10 to Week 12

• Self-reported craving for cocaine as assessed by average Brief Substance Craving Scale score across 12 weeks of treatment

  The Brief Substance Craving Scale (BSCS) score ranges from 0 to 4, with a higher score indicating greater craving. Participants will be assessed by BSCS once per week for 12 weeks, and the average BSCS score over the 12 weeks will be reported.

  From Week 1 to Week 12

• Self-reported craving for cocaine as assessed by average Visual Analogue Scale score across 12 weeks of treatment

  The Visual Analogue Scale (VAS) score ranges from 0 to 100, with a higher score indicating greater craving. Participants will be assessed by VAS once per week for 12 weeks, and the average VAS score over the 12 weeks will be reported.

  From Week 1 to Week 12

Secondary Outcomes (5)

• Total percentage of days abstinent during treatment as assessed by self-reported non-use days confirmed by cocaine-negative urine drug screen results

  From Week 1 to Week 12

• Total percentage of cocaine-negative urine drug screens during treatment as assessed by number of cocaine-negative samples out of total number of urine samples provided

  From Week 1 to Week 12

• Functional health status as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) global health summary score

  Week 0

• Functional health status as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) global health summary score

  Week 4

• Functional health status as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) global health summary score

  Week 12

Study Arms (2)

CBT + pioglitazone

ACTIVE COMPARATOR

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.

Behavioral: Cognitive Behavioral Therapy (CBT); Drug: Pioglitazone

CBT + placebo

PLACEBO COMPARATOR

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.

Behavioral: Cognitive Behavioral Therapy (CBT); Drug: Placebo

Interventions

Cognitive Behavioral Therapy (CBT) 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.

Also known as: CBT

CBT + pioglitazone; CBT + placebo

Pioglitazone 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.

Also known as: Actos

CBT + pioglitazone

Placebo DRUG

Placebo capsules will be filled with corn starch and riboflavin.

Also known as: Corn Starch

CBT + placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

UTHealth Center for Neurobehavioral Research on Addiction

Houston, Texas, 77054, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Cognitive Behavioral Therapy; Pioglitazone; Starch

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Polysaccharides

Study Officials

• Joy M Schmitz, PhD

  UT Houston

  PRINCIPAL INVESTIGATOR

• Scott D Lane, PhD

  UT Houston

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Faillace Chair, and Director for the Center for Neurobehavioral Research on Addiction

Study Record Dates

• First Submitted: April 8, 2021
• First Posted: April 13, 2021
• Study Start: August 23, 2021
• Primary Completion: September 26, 2025
• Study Completion: October 15, 2025
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)