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PPARγ Agonist Treatment for Cocaine Dependence

Phase 1
Completed
Conditions
Cocaine Use Disorder
Alcohol Use Disorder
Interventions
Drug: Placebo
Drug: Pioglitazone
Behavioral: Therapy
Behavioral: Contingency Management
Registration Number
NCT02774343
Lead Sponsor
The University of Texas Health Science Center, Houston
Brief Summary

The purpose of this research study is to determine whether a medication called pioglitazone (trade name Actos) can reduce behavioral problems associated with cocaine use, improve brain structural changes associated with cocaine use and reduce cocaine craving and drug use in cocaine dependent patients.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria
  • DSM-IV criteria for cocaine dependence
  • At least one cocaine positive urine during screening
  • Female subjects: a negative pregnancy test
  • Be in acceptable health on the basis of interview, medical history and physical exam
  • 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 generally locate their whereabouts.
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Exclusion Criteria
  • Current Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnosis of any psychoactive substance dependence other than cocaine marijuana, alcohol, or nicotine
  • Any serious medical or psychiatric illness and/or clinically significant abnormal laboratory value, which in the judgment of the Principal Investigator or his/her designee would make study participation unsafe, or would make treatment compliance difficult or put the study staff at undue risk
  • Significant current suicidal or homicidal ideation
  • Medical conditions contraindicating pioglitazone pharmacotherapy (e.g., congestive heart failure as determined by Framingham criteria, clinically significant edema, clinically significant liver disease, hypoglycemia, diabetes, history of bladder cancer)
  • Taking medications known to have significant drug interactions with the study medication (CYP2C8 inhibitors or inducers, antihyperglycemic medications)
  • Currently being treated for substance misuse with medication
  • Conditions of probation or parole requiring reports of drug use to officers of the court
  • Impending incarceration
  • Pregnant or planning to become pregnant during the course of the trial or nursing for female patients
  • Inability to read, write, or speak English (many of the research instruments in this study only exist in English)
  • Having plans to leave the immediate geographical area within 3 months
  • Unwillingness to sign a written informed consent form
  • Unwillingness to use a barrier method of birth control during the study for female patients
  • History of pacemaker or metal implants or welding or metal work without protective eyewear (for risk of MRI scans).
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pioglitazone + Therapy + Contingency ManagementTherapySubjects randomized to pioglitazone begin with a starting dose of 15 mg daily administered. The dose will be titrated up to 30mg on the second week and 45 mg on the third week of the study. Subjects will remain on 45 mg of pioglitazone until the end of week 12. At the end of week 12 the study medication will be discontinued.
Placebo + Therapy + Contingency ManagementPlaceboSubjects randomized to placebo receive placebo capsules once daily across all twelve weeks of the study.
Pioglitazone + Therapy + Contingency ManagementContingency ManagementSubjects randomized to pioglitazone begin with a starting dose of 15 mg daily administered. The dose will be titrated up to 30mg on the second week and 45 mg on the third week of the study. Subjects will remain on 45 mg of pioglitazone until the end of week 12. At the end of week 12 the study medication will be discontinued.
Placebo + Therapy + Contingency ManagementContingency ManagementSubjects randomized to placebo receive placebo capsules once daily across all twelve weeks of the study.
Placebo + Therapy + Contingency ManagementTherapySubjects randomized to placebo receive placebo capsules once daily across all twelve weeks of the study.
Pioglitazone + Therapy + Contingency ManagementPioglitazoneSubjects randomized to pioglitazone begin with a starting dose of 15 mg daily administered. The dose will be titrated up to 30mg on the second week and 45 mg on the third week of the study. Subjects will remain on 45 mg of pioglitazone until the end of week 12. At the end of week 12 the study medication will be discontinued.
Primary Outcome Measures
NameTimeMethod
Cue Reactivity as Assessed by a Visual Analogue Scale (VAS) of Cocaine CravingBaseline, week 2, week 4, week 6, week 8, week 10, week 12

Every two weeks, visual analog scale ratings of craving (VAS craving) consisting of 100 mm line, anchored by 0 "not at all" and 100 "extremely," were used to assess cocaine craving right now, craving on average in the past week, and the worst craving in the past week. Data were analyzed as a total score, which is the sum of the scores for the three questions.

Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Anterior Thalamic Radiation)Baseline and Week 12

DTI scans were acquired on a Philips Integra 3T magnet. Fractional anisotropy (FA) is a summary measure of the integrity of white matter neurons that provides a dimensionless index of the expected movement of water molecules inside and across the neuron. Higher values of FA indicate better neuronal integrity (that is, less movement of water across the neuron). There is no range of values, as this is a dimensionless index.

Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Splenium of Corpus Callosum)Baseline and Week 12

DTI scans were acquired on a Philips Integra 3T magnet. Fractional anisotropy (FA) is a summary measure of the integrity of white matter neurons that provides a dimensionless index of the expected movement of water molecules inside and across the neuron. Higher values of FA indicate better neuronal integrity (that is, less movement of water across the neuron). There is no range of values, as this is a dimensionless index.

Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Posterior Thalamic Radiation)Baseline and Week 12

DTI scans were acquired on a Philips Integra 3T magnet. Fractional anisotropy (FA) is a summary measure of the integrity of white matter neurons that provides a dimensionless index of the expected movement of water molecules inside and across the neuron. Higher values of FA indicate better neuronal integrity (that is, less movement of water across the neuron). There is no range of values, as this is a dimensionless index.

Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Genu of Corpus Callosum)Baseline and Week 12

DTI scans were acquired on a Philips Integra 3T magnet. Fractional anisotropy (FA) is a summary measure of the integrity of white matter neurons that provides a dimensionless index of the expected movement of water molecules inside and across the neuron. Higher values of FA indicate better neuronal integrity (that is, less movement of water across the neuron). There is no range of values, as this is a dimensionless index.

Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - External Capsule)Baseline and Week 12

DTI scans were acquired on a Philips Integra 3T magnet. Fractional anisotropy (FA) is a summary measure of the integrity of white matter neurons that provides a dimensionless index of the expected movement of water molecules inside and across the neuron. Higher values of FA indicate better neuronal integrity (that is, less movement of water across the neuron). There is no range of values, as this is a dimensionless index.

Craving as Assessed by the Obsessive Compulsive Drug Use Scale (OCDUS)Weeks 1-12

The obsessive compulsive drug use scale (OCDUS) measures the level of craving for cocaine during the past week. The mean score over all time points is reported in this outcome measure (i.e., a summary score is reported). The scale was administered once weekly. It consists of 12 items. The score range is 0 to 60, and higher scores indicates greater craving.

Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Cingulum)Baseline and Week 12

DTI scans were acquired on a Philips Integra 3T magnet. Fractional anisotropy (FA) is a summary measure of the integrity of white matter neurons that provides a dimensionless index of the expected movement of water molecules inside and across the neuron. Higher values of FA indicate better neuronal integrity (that is, less movement of water across the neuron). There is no range of values, as this is a dimensionless index.

Craving as Assessed by the Brief Substance Craving Scale (BSCS)Baseline, week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12

The brief substance craving scale (BSCS) is a 16-item, self-report instrument assesses craving for cocaine and other substances of abuse over a 24 hour period. The domains of intensity, frequency, and duration are recorded on a five-point Likert scale. The range of scores for each domain is 0 to 4, and the total score is the sum of all three domains. The total score range is 0 to 12, and higher scores indicate higher craving (worse outcome.)

Secondary Outcome Measures
NameTimeMethod
Cocaine Use as Assessed by Percentage of Self-reports That Indicate Cocaine UseWeeks 1-12

A modified Timeline Followback (TLFB) procedure was used to assess cocaine use. The mean percentage over all time points is reported in this outcome measure. Self-reports were collected once weekly.

Feasibility - Subject Retention as Assessed by Number of Participants Who Completed All 12 Weeks of the Studyweek 12
Feasibility - Tolerability as Assessed by Number of Participants Reporting Side Effectsweek 12
Feasibility - Tolerability as Assessed by Number of Participants With Serious Adverse Eventsweek 12
Feasibility - Medication Compliance as Assessed by Percentage of Self-reports That Indicate Capsules Were Takenweeks 1 - 12

A modified Timeline Followback (TLFB) procedure was used for self-reports. The percentage over all time points is reported in this outcome measure. Self-reports were collected once weekly.

Feasibility - Medication Compliance as Assessed by Percentage of Urine Samples That Were Riboflavin-Positiveweeks 1 - 12

Riboflavin was added to pill capsules as a marker of medication compliance. The percentage over all time points is reported in this outcome measure. Urine samples were collected once weekly.

Cocaine Use as Assessed by Percentage of Urine Samples That Were Cocaine-positiveWeeks 1-12

The mean percentage over all time points is reported in this outcome measure. Urine samples were collected once weekly.

Trial Locations

Locations (1)

The University of Texas Health Science Center at Houston

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Houston, Texas, United States

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