Back to resultsPPARγ Agonist Treatment for Cocaine Dependence
Primary Purpose
Cocaine Use Disorder, Alcohol Use Disorder
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pioglitazone
Placebo
Therapy
Contingency Management
Sponsored by
About this trial
This is an interventional treatment trial for Cocaine Use Disorder
Eligibility Criteria
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.
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).
Sites / Locations
- The University of Texas Health Science Center at Houston
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Pioglitazone + Therapy + Contingency Management
Placebo + Therapy + Contingency Management
Arm Description
Subjects 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.
Subjects randomized to placebo receive placebo capsules once daily across all twelve weeks of the study.
Outcomes
Primary Outcome Measures
Craving as Assessed by the Brief Substance Craving Scale (BSCS)
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.)
Craving as Assessed by the Obsessive Compulsive Drug Use Scale (OCDUS)
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.
Cue Reactivity as Assessed by a Visual Analogue Scale (VAS) of Cocaine Craving
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 - Posterior Thalamic Radiation)
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 - Anterior Thalamic Radiation)
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)
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)
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)
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 - Cingulum)
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.
Secondary Outcome Measures
Feasibility - Subject Retention as Assessed by Number of Participants Who Completed All 12 Weeks of the Study
Feasibility - Medication Compliance as Assessed by Percentage of Urine Samples That Were Riboflavin-Positive
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.
Feasibility - Medication Compliance as Assessed by Percentage of Self-reports That Indicate Capsules Were Taken
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 - Tolerability as Assessed by Number of Participants Reporting Side Effects
Feasibility - Tolerability as Assessed by Number of Participants With Serious Adverse Events
Cocaine Use as Assessed by Percentage of Urine Samples That Were Cocaine-positive
The mean percentage over all time points is reported in this outcome measure. Urine samples were collected once weekly.
Cocaine Use as Assessed by Percentage of Self-reports That Indicate Cocaine Use
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.
Full Information
NCT ID
NCT02774343
First Posted
May 6, 2016
Last Updated
March 26, 2018
Sponsor
The University of Texas Health Science Center, Houston
Collaborators
National Institute on Drug Abuse (NIDA)
1. Study Identification
Unique Protocol Identification Number
NCT02774343
Brief Title
PPARγ Agonist Treatment for Cocaine Dependence
Official Title
PPARγ Agonist Treatment for Cocaine Dependence
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
Collaborators
National Institute on Drug Abuse (NIDA)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cocaine Use Disorder, Alcohol Use Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pioglitazone + Therapy + Contingency Management
Arm Type
Experimental
Arm Description
Subjects 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.
Arm Title
Placebo + Therapy + Contingency Management
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to placebo receive placebo capsules once daily across all twelve weeks of the study.
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos
Intervention Description
Subjects 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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
corn starch
Intervention Description
Subjects randomized to placebo receive placebo capsules once daily across all twelve weeks of the study.
Intervention Type
Behavioral
Intervention Name(s)
Therapy
Intervention Description
Cognitive-behavioral therapy 1 hour per week
Intervention Type
Behavioral
Intervention Name(s)
Contingency Management
Intervention Description
Prize-based contingency management for attendance
Primary Outcome Measure Information:
Title
Craving as Assessed by the Brief Substance Craving Scale (BSCS)
Description
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.)
Time Frame
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
Title
Craving as Assessed by the Obsessive Compulsive Drug Use Scale (OCDUS)
Description
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.
Time Frame
Weeks 1-12
Title
Cue Reactivity as Assessed by a Visual Analogue Scale (VAS) of Cocaine Craving
Description
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.
Time Frame
Baseline, week 2, week 4, week 6, week 8, week 10, week 12
Title
Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Posterior Thalamic Radiation)
Description
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.
Time Frame
Baseline and Week 12
Title
Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Anterior Thalamic Radiation)
Description
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.
Time Frame
Baseline and Week 12
Title
Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Splenium of Corpus Callosum)
Description
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.
Time Frame
Baseline and Week 12
Title
Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Genu of Corpus Callosum)
Description
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.
Time Frame
Baseline and Week 12
Title
Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - External Capsule)
Description
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.
Time Frame
Baseline and Week 12
Title
Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Cingulum)
Description
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.
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
Feasibility - Subject Retention as Assessed by Number of Participants Who Completed All 12 Weeks of the Study
Time Frame
week 12
Title
Feasibility - Medication Compliance as Assessed by Percentage of Urine Samples That Were Riboflavin-Positive
Description
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.
Time Frame
weeks 1 - 12
Title
Feasibility - Medication Compliance as Assessed by Percentage of Self-reports That Indicate Capsules Were Taken
Description
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.
Time Frame
weeks 1 - 12
Title
Feasibility - Tolerability as Assessed by Number of Participants Reporting Side Effects
Time Frame
week 12
Title
Feasibility - Tolerability as Assessed by Number of Participants With Serious Adverse Events
Time Frame
week 12
Title
Cocaine Use as Assessed by Percentage of Urine Samples That Were Cocaine-positive
Description
The mean percentage over all time points is reported in this outcome measure. Urine samples were collected once weekly.
Time Frame
Weeks 1-12
Title
Cocaine Use as Assessed by Percentage of Self-reports That Indicate Cocaine Use
Description
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.
Time Frame
Weeks 1-12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joy M Schmitz, PhD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
PPARγ Agonist Treatment for Cocaine Dependence
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