PPARγ Agonist Treatment for Cocaine Dependence

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02774343

Enrollment

Registered

2016-05-17

Start date

2012-08-31

Completion date

2015-06-30

Last updated

2018-04-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alcohol Use Disorder, Cocaine Use Disorder

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.

Interventions

DRUGPioglitazone

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.

DRUGPlacebo

Subjects randomized to placebo receive placebo capsules once daily across all twelve weeks of the study.

BEHAVIORALTherapy

Cognitive-behavioral therapy 1 hour per week

BEHAVIORALContingency Management

Prize-based contingency management for attendance

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
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 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.
Cue Reactivity as Assessed by a Visual Analogue Scale (VAS) of Cocaine Craving	Baseline, 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 - 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 - 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 - 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 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

Measure	Time frame	Description
Feasibility - Medication Compliance as Assessed by Percentage of Urine Samples That Were Riboflavin-Positive	weeks 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.
Feasibility - Medication Compliance as Assessed by Percentage of Self-reports That Indicate Capsules Were Taken	weeks 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 - Tolerability as Assessed by Number of Participants Reporting Side Effects	week 12	—
Feasibility - Tolerability as Assessed by Number of Participants With Serious Adverse Events	week 12	—
Cocaine Use as Assessed by Percentage of Urine Samples That Were Cocaine-positive	Weeks 1-12	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	Weeks 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 Study	week 12	—

Countries

United States

Participant flow

Participants by arm

Arm	Count
Pioglitazone + Therapy + Contingency Management Pioglitazone: 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. Therapy: Cognitive-behavioral therapy 1 hour per week Contingency Management: Prize-based contingency management for attendance	15
Placebo + Therapy + Contingency Management Placebo: Subjects randomized to placebo receive placebo capsules once daily across all twelve weeks of the study. Therapy: Cognitive-behavioral therapy 1 hour per week Contingency Management: Prize-based contingency management for attendance	15
Total	30

Baseline characteristics

Characteristic	Pioglitazone + Therapy + Contingency Management	Placebo + Therapy + Contingency Management	Total
Age, Continuous	48.3 years STANDARD_DEVIATION 7.1	47.4 years STANDARD_DEVIATION 7.8	47.8 years STANDARD_DEVIATION 7.45
Region of Enrollment United States	15 Participants	15 Participants	30 Participants
Sex: Female, Male Female	4 Participants	4 Participants	8 Participants
Sex: Female, Male Male	11 Participants	11 Participants	22 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 12	0 / 14
serious Total, serious adverse events	0 / 12	0 / 14

Outcome results

Primary

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.