PPARγ Agonist Treatment for Cocaine Dependence

NCT02774343 | Completed Phase 1 Results DMC

• 2 other identifiers: HSC-MS-12-0421P50DA009262
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Cocaine Use Disorder; Alcohol Use Disorder

Outcome Measures

Primary Outcomes (9)

• 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.)

  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

• 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.

  Weeks 1-12

• 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.

  Baseline, week 2, week 4, week 6, week 8, week 10, week 12

• 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.

  Baseline and Week 12

• 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.

  Baseline and Week 12

• 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.

  Baseline and Week 12

• 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.

  Baseline and Week 12

• 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.

  Baseline and Week 12

• 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.

  Baseline and Week 12

Secondary Outcomes (7)

• Feasibility - Subject Retention as Assessed by Number of Participants Who Completed All 12 Weeks of the Study

  week 12

• Feasibility - Medication Compliance as Assessed by Percentage of Urine Samples That Were Riboflavin-Positive

  weeks 1 - 12

• Feasibility - Medication Compliance as Assessed by Percentage of Self-reports That Indicate Capsules Were Taken

  weeks 1 - 12

• 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

Study Arms (2)

Pioglitazone + Therapy + Contingency Management

EXPERIMENTAL

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; Behavioral: Therapy; Behavioral: Contingency Management

Placebo + Therapy + Contingency Management

PLACEBO COMPARATOR

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

Drug: Placebo; Behavioral: Therapy; Behavioral: Contingency Management

Interventions

Pioglitazone DRUG

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.

Also known as: Actos

Pioglitazone + Therapy + Contingency Management

Placebo DRUG

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

Also known as: corn starch

Placebo + Therapy + Contingency Management

Therapy BEHAVIORAL

Cognitive-behavioral therapy 1 hour per week

Pioglitazone + Therapy + Contingency Management; Placebo + Therapy + Contingency Management

Contingency Management BEHAVIORAL

Prize-based contingency management for attendance

Pioglitazone + Therapy + Contingency Management; Placebo + Therapy + Contingency Management

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Pioglitazone; Starch; Therapeutics

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Polysaccharides

Limitations and Caveats

Small sample size; restricted measurement battery; comorbid CUD \& AUD; single dose; for DTI, Bayesian parameter estimates of variance in the simple effects may be underestimated; generalizability of pioglitazone to other substances of abuse unknown.

Results Point of Contact

• Title: Joy M. Schmitz, PhD
• Organization: The University of Texas Health Science Center at Houston

Joy.M.Schmitz@uth.tmc.edu

713-486-2867

Study Officials

• Joy M Schmitz, PhD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 6, 2016
• First Posted: May 17, 2016
• Study Start: August 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: April 26, 2018
• Results First Posted: April 26, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)