PPARγ Agonist Treatment for Cocaine Dependence

• ClinicalTrials.gov Identifier: NCT02774343
• Recruitment Status: Completed
• First Posted: May 17, 2016
• Results First Posted: April 26, 2018
• Last Update Posted: April 26, 2018
• Sponsor: The University of Texas Health Science Center, Houston
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Joy Schmitz, The University of Texas Health Science Center, Houston

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.

Condition or disease	Intervention/treatment	Phase
Cocaine Use Disorder; Alcohol Use Disorder	Drug: Pioglitazone; Drug: Placebo; Behavioral: Therapy; Behavioral: Contingency Management	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: PPARγ Agonist Treatment for Cocaine Dependence
• Study Start Date: August 2012
• Actual Primary Completion Date: June 2015
• Actual Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pioglitazone + Therapy + Contingency Management; 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.	Drug: 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.; Other Name: Actos; Behavioral: Therapy; Cognitive-behavioral therapy 1 hour per week; Behavioral: Contingency Management; Prize-based contingency management for attendance
Placebo Comparator: Placebo + Therapy + Contingency Management; Subjects randomized to placebo receive placebo capsules once daily across all twelve weeks of the study.	Drug: Placebo; Subjects randomized to placebo receive placebo capsules once daily across all twelve weeks of the study.; Other Name: corn starch; Behavioral: Therapy; Cognitive-behavioral therapy 1 hour per week; Behavioral: Contingency Management; Prize-based contingency management for attendance

Outcome Measures

Primary Outcome Measures :

1. Craving as Assessed by the Brief Substance Craving Scale (BSCS) [ 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 ]
   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.)
2. Craving as Assessed by the Obsessive Compulsive Drug Use Scale (OCDUS) [ Time Frame: 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.
3. Cue Reactivity as Assessed by a Visual Analogue Scale (VAS) of Cocaine Craving [ Time Frame: 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.
4. Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Posterior Thalamic Radiation) [ Time Frame: 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.
5. Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Anterior Thalamic Radiation) [ Time Frame: 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.
6. Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Splenium of Corpus Callosum) [ Time Frame: 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.
7. Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Genu of Corpus Callosum) [ Time Frame: 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.
8. Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - External Capsule) [ Time Frame: 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.
9. Brain White Matter (WM) Integrity as Assessed by Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Value (Region - Cingulum) [ Time Frame: 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.

Secondary Outcome Measures :

1. Feasibility - Subject Retention as Assessed by Number of Participants Who Completed All 12 Weeks of the Study [ Time Frame: week 12 ]
2. Feasibility - Medication Compliance as Assessed by Percentage of Urine Samples That Were Riboflavin-Positive [ Time Frame: 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.
3. Feasibility - Medication Compliance as Assessed by Percentage of Self-reports That Indicate Capsules Were Taken [ Time Frame: 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.
4. Feasibility - Tolerability as Assessed by Number of Participants Reporting Side Effects [ Time Frame: week 12 ]
5. Feasibility - Tolerability as Assessed by Number of Participants With Serious Adverse Events [ Time Frame: week 12 ]
6. Cocaine Use as Assessed by Percentage of Urine Samples That Were Cocaine-positive [ Time Frame: Weeks 1-12 ]
   The mean percentage over all time points is reported in this outcome measure. Urine samples were collected once weekly.
7. Cocaine Use as Assessed by Percentage of Self-reports That Indicate Cocaine Use [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

United States, Texas

The University of Texas Health Science Center at Houston

Houston, Texas, United States, 77030

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Joy M Schmitz, PhD; The University of Texas Health Science Center, Houston

More Information

• Responsible Party: Joy Schmitz, Professor, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT02774343
• Other Study ID Numbers: HSC-MS-12-0421; P50DA009262 ( U.S. NIH Grant/Contract )
• First Posted: May 17, 2016
• Results First Posted: April 26, 2018
• Last Update Posted: April 26, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Disease; Alcoholism; Cocaine-Related Disorders; Pathologic Processes; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pioglitazone; Hypoglycemic Agents; Physiological Effects of Drugs