Pioglitazone + Cognitive-Behavioral Therapy for Cocaine Use Disorder

Overseen By Joy M Schmitz, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: CYP2C8 inhibitors, Antihyperglycemics

Disqualifiers: Suicidal ideation, Diabetes, Heart failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining pioglitazone, a medication typically used for diabetes, with cognitive behavioral therapy (CBT) can help individuals who have recently stopped using cocaine to maintain abstinence. The study compares the effects of CBT with pioglitazone to CBT with a placebo (an inactive pill) to determine which is more effective. Individuals diagnosed with cocaine use disorder who have recently used cocaine might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that would negatively interact with pioglitazone, such as certain diabetes medications or CYP2C8 inhibitors or inducers.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining pioglitazone with Cognitive Behavioral Therapy (CBT) is generally safe for treating cocaine addiction. One study found that pioglitazone helped reduce the urge to use cocaine and seemed to improve brain function in those receiving this combined treatment. Importantly, this treatment has been safely used in humans before, with few reports of serious side effects. This suggests that pioglitazone, along with CBT, offers a promising option for those seeking to maintain recovery from cocaine use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for cocaine use disorder, which primarily focus on behavioral therapies or medications that address cravings and withdrawal, the combination of pioglitazone with Cognitive Behavioral Therapy (CBT) introduces a novel approach. Pioglitazone, traditionally used for diabetes, is thought to have neuroprotective effects and may help reduce inflammation in the brain, potentially addressing the neurological impacts of cocaine use. Researchers are excited because this treatment could target the brain's response to cocaine, potentially enhancing the effectiveness of CBT and offering a new avenue for recovery that current options don't provide.

What evidence suggests that this trial's treatments could be effective for cocaine use disorder?

Research has shown that using pioglitazone with Cognitive Behavioral Therapy (CBT) can reduce cocaine cravings and improve brain health over time. In this trial, some participants will receive CBT with pioglitazone, while others will receive CBT with a placebo. Studies have found that people taking pioglitazone tend to experience fewer cocaine cravings. Additionally, pioglitazone is associated with better brain health, particularly in areas crucial for brain function. This treatment combination is generally well-tolerated by those trying to quit cocaine. Overall, early evidence suggests it may help individuals remain cocaine-free. ^{1 2 3 5 6}

Who Is on the Research Team?

Joy M Schmitz, PhD

Principal Investigator

UT Houston

Scott D Lane, PhD

Principal Investigator

UT Houston

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 who have recently used cocaine, as confirmed by a drug test. Participants must be physically and mentally stable, understand the consent form, agree to use effective birth control if female and not pregnant or breastfeeding. They should also commit to a 5-day detox program and provide contacts for locating them.

Inclusion Criteria

Be able to provide the names of at least 2 persons who can consistently locate their whereabouts

Be able to understand the consent form and provide written informed consent

Report recent cocaine use, verified by at least one positive urine drug screen for the cocaine metabolite, benzoylecgonine, during intake

Exclusion Criteria

Be concurrently enrolled in other addiction treatment services aside from smoking cessation

Have conditions of probation or parole requiring reports of drug use to officers of the court

Have medical contraindications to MRI/DTI scans (e.g., history of pacemaker, metal implants, or welding/metal work without protective eyewear)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Detoxification

Participants undergo a 5-day inpatient detoxification process

1 week

Inpatient stay

Treatment

Participants receive Cognitive Behavioral Therapy and either pioglitazone or placebo for 12 weeks

12 weeks

Twice weekly visits during weeks 1-4, once weekly visits during weeks 5-12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Behavioral Therapy (CBT)
• Pioglitazone

Trial Overview

The study tests whether pioglitazone combined with cognitive-behavioral therapy (CBT) can help prevent relapse in individuals recovering from cocaine use disorder. Participants will either receive pioglitazone or a placebo alongside CBT sessions.

How Is the Trial Designed?

Group I: CBT + pioglitazone Active Control 2 Interventions

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 II: CBT + placebo Placebo Group 2 Interventions

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.

Cognitive Behavioral Therapy (CBT) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cognitive Behavioral Therapy for:

• Chronic pain
• Anxiety disorders
• Depressive disorders
• Trauma-related disorders

Approved in European Union as Cognitive Behavioural Therapy for:

• Chronic pain
• Anxiety disorders
• Depressive disorders
• Trauma-related disorders

Approved in Canada as Cognitive Behavioral Therapy for:

• Chronic pain
• Anxiety disorders
• Depressive disorders
• Trauma-related disorders

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study involving 10 participants, tiagabine, a GABA reuptake inhibitor, was tested for its safety and effects when combined with oral cocaine, but it did not significantly alter the effects of cocaine on behavior or cardiovascular responses.

The results indicate that tiagabine is unlikely to be effective in preventing cocaine use, as it did not block the reinforcing or stimulant effects typically associated with cocaine consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute administration of the GABA reuptake inhibitor tiagabine does not alter the effects of oral cocaine in humans. Lile, JA., Stoops, WW., Glaser, PE., et al.[2019]

A phase 2 randomized clinical trial is being conducted to assess whether pioglitazone, a PPAR-γ agonist, can improve cognitive function and white matter integrity in individuals recovering from cocaine use disorder, potentially enhancing the effectiveness of cognitive-behavioral therapy (CBT).

The study aims to evaluate how improvements in cognitive function and white matter integrity relate to responses in CBT, which could lead to pioglitazone being developed as a new treatment option for preventing relapse in cocaine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting white matter neuroprotection as a relapse prevention strategy for treatment of cocaine use disorder: Design of a mechanism-focused randomized clinical trial. Schmitz, JM., Lane, SD., Weaver, MF., et al.[2022]

Cognitive-behavioral therapies (CBTs) have shown significant effectiveness in treating cocaine dependence, especially since there are no widely effective medications available for this condition.

Various CBT approaches, such as community reinforcement with vouchers and motivational interviewing, are being actively researched and have the potential to improve treatment outcomes for individuals with cocaine use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cognitive-behavioral therapy for the treatment of cocaine dependence]. Trujols, J., Luquero, E., Siñol, N., et al.[2018]

In a pilot trial involving 30 adults with cocaine use disorder, pioglitazone (PIO) significantly reduced cocaine craving and improved brain white matter integrity compared to placebo, indicating its potential efficacy as a treatment.

The study demonstrated good feasibility for pioglitazone, with an 80% treatment completion rate and no serious adverse events reported, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double-blind randomized controlled pilot trial. Schmitz, JM., Green, CE., Hasan, KM., et al.[2022]

Cocaine use can lead to a compulsive pattern of abuse, particularly when taken intravenously or by freebasing, resulting in significant psychological and physical effects, including increased heart rate and blood pressure, as well as feelings of euphoria followed by anxiety and depression.

Effective treatment for cocaine abuse involves stopping all use through various strategies, and may include the use of medications like antidepressants to manage withdrawal symptoms, alongside psychotherapeutic approaches for those with underlying personality disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cocaine abuse and its treatment. Resnick, RB., Resnick, EB.[2019]

In a 12-week study involving 141 participants with cocaine dependence, tiagabine (20 mg/day) was found to be safe and well tolerated, with no significant adverse effects reported.

Despite improvements in cocaine craving and global functioning for all participants, tiagabine did not show a strong effect in reducing cocaine use compared to placebo, indicating limited efficacy for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled trial of tiagabine for the treatment of cocaine dependence. Winhusen, T., Somoza, E., Ciraulo, DA., et al.[2018]

In a study of 99 outpatients with cocaine dependence, the combination of contingency management (CM) and cognitive behavioral therapy (CBT) led to the best outcomes for cocaine abstinence, while disulfiram did not enhance these results.

The findings suggest that while CM significantly improves treatment outcomes, disulfiram does not provide additional benefits when used alongside CBT for cocaine use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized factorial trial of disulfiram and contingency management to enhance cognitive behavioral therapy for cocaine dependence. Carroll, KM., Nich, C., Petry, NM., et al.[2018]

In a study of 140 adults with cocaine use disorder undergoing web-based cognitive-behavior therapy (CBT), higher baseline positive affect (PA) was linked to less frequent cocaine use during treatment, suggesting that enhancing positive emotions may improve treatment outcomes.

While negative affect (NA) scores decreased over time in both CBT and treatment as usual, higher NA during treatment was associated with increased cocaine use, indicating that managing negative emotions could be crucial for successful recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive and negative affect in cocaine use disorder treatment: Change across time and relevance to treatment outcome. Decker, SE., Morie, KP., Malin-Mayo, B., et al.[2020]

In a study involving 74 crack-cocaine dependent outpatients, topiramate (200mg/day) was found to be safe and well-tolerated, but it did not improve treatment retention or reduce cocaine use when added to cognitive behavioral therapy (CBT).

Exploratory analyses indicated that topiramate may help reduce cocaine use specifically in patients with comorbid opioid dependence, suggesting that its effectiveness might be limited to certain subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of crack-cocaine dependence with topiramate: a randomized controlled feasibility trial in The Netherlands. Nuijten, M., Blanken, P., van den Brink, W., et al.[2022]

In a study of 193 cocaine-using patients undergoing methadone maintenance, combining contingency management (CM) with cognitive-behavioral therapy (CBT) showed initial dampening of CM effects during treatment, but post-treatment benefits emerged, particularly at 3 months compared to 12 months.

Participants who received CBT were more likely to acknowledge their cocaine use and its effects, and they reported higher employment rates, suggesting that CBT may enhance long-term recovery outcomes when combined with CM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive-behavioral therapy plus contingency management for cocaine use: findings during treatment and across 12-month follow-up. Epstein, DH., Hawkins, WE., Covi, L., et al.[2019]

In a randomized clinical trial with 101 cocaine-dependent individuals on methadone, those who had access to computer-based cognitive-behavioral therapy (CBT4CBT) were significantly more likely to achieve 3 or more consecutive weeks of abstinence from cocaine (36% vs. 17%).

The study demonstrated that CBT4CBT not only improved immediate treatment outcomes but also showed durable effects, with continued improvement observed 6 months after treatment, highlighting its potential as an effective and easily disseminable adjunct to traditional addiction treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computer-assisted delivery of cognitive-behavioral therapy: efficacy and durability of CBT4CBT among cocaine-dependent individuals maintained on methadone. Carroll, KM., Kiluk, BD., Nich, C., et al.[2023]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04843046

NCT04843046 | Pioglitazone as an Adjunct to Cognitive- ...

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 ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5593771/

PPAR-gamma agonist pioglitazone modifies craving ...

Patients receiving pioglitazone show a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in ...

3.

withpower.com

withpower.com/trial/phase-3-recurrence-3-2021-af65f

Pioglitazone + Cognitive-Behavioral Therapy for Cocaine ...

Research suggests that Pioglitazone, used in combination with Cognitive-Behavioral Therapy, is generally well-tolerated in humans for treating cocaine use ...

4.

clinicaltrial.be

clinicaltrial.be/fr/details/45196?only_active=0&only_eligible=0&only_recruiting=0&per_page=100

Pioglitazone as an Adjunct to Cognitive-Behavioral Therap...

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 ...

5.

med.uth.edu

med.uth.edu/psychiatry/pioglitazone-with-cognitive-behavioral-therapy-for-cocaine-relapse-prevention/

Pioglitazone with Cognitive-Behavioral Therapy for Cocaine ...

The purpose of this study is to see how well pioglitazone improves the chances of recovery in people who have recently stopped using cocaine.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8678331/

Design of a mechanism-focused randomized clinical trial

This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from ...