PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder

A double-blind randomized controlled pilot trial

Joy M. Schmitz, Charles E. Green, Khader M. Hasan, Jessica Vincent, Robert Suchting, Michael F. Weaver, F. Gerard Moeller, Ponnada A. Narayana, Kathryn Cunningham, Kelly Dineley, Scott D. Lane

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background and aims: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance and tolerability were evaluated. Design: Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC). Setting: Single-site out-patient treatment research clinic in Houston, TX, USA. Participants: Thirty treatment-seeking adults, 18 to 60 years old, with CUD. Eighteen participants (8 = PIO; 10 = PLC) completed diffusion tensor imaging (DTI) of WM integrity at pre-/post-treatment. Intervention: Study medication was dispensed at thrice weekly visits along with once-weekly cognitive behavioral therapy for 12 weeks. Measurements: Measures of target engagement mechanisms of interest included cocaine craving assessed by the Brief Substance Craving Scale (BSCS), the Obsessive Compulsive Drug Use Scale (OCDUS), a visual analog scale (VAS) and change in WM integrity. Feasibility measures included number completing treatment, medication compliance (riboflavin detection) and tolerability (side effects, serious adverse events). Findings: Target engagement change in mechanisms of interest, defined as a ≥ 0.75 Bayesian posterior probability of an interaction existing favoring PIO over PLC, was demonstrated on measures of craving (BSCS, VAS) and WM integrity indexed by fractional anisotropy (FA) values. Outcomes indicated greater decrease in craving and greater increase in FA values in the PIO group. Feasibility was demonstrated by high completion rates among those starting treatment (21/26 = 80%) and medication compliance (≥ 80%). There were no reported serious adverse events for PIO. Conclusions: Compared with placebo, patients receiving pioglitazone show a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in treatment. Pioglitazone shows good feasibility as a treatment for cocaine use disorder.

Original languageEnglish (US)
JournalAddiction
DOIs
StateAccepted/In press - 2017

Fingerprint

pioglitazone
PPAR gamma
Cocaine
Randomized Controlled Trials
Brain
Medication Adherence
Placebos
Anisotropy
Therapeutics
Visual Analog Scale
Craving
White Matter
Diffusion Tensor Imaging
Riboflavin
Cognitive Therapy

Keywords

  • Bayesian statistics
  • Cocaine use disorder
  • Craving
  • Pioglitazone
  • PPAR-gamma
  • Target engagement
  • White matter integrity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health

Cite this

PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder : A double-blind randomized controlled pilot trial. / Schmitz, Joy M.; Green, Charles E.; Hasan, Khader M.; Vincent, Jessica; Suchting, Robert; Weaver, Michael F.; Moeller, F. Gerard; Narayana, Ponnada A.; Cunningham, Kathryn; Dineley, Kelly; Lane, Scott D.

In: Addiction, 2017.

Research output: Contribution to journalArticle

Schmitz, Joy M. ; Green, Charles E. ; Hasan, Khader M. ; Vincent, Jessica ; Suchting, Robert ; Weaver, Michael F. ; Moeller, F. Gerard ; Narayana, Ponnada A. ; Cunningham, Kathryn ; Dineley, Kelly ; Lane, Scott D. / PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder : A double-blind randomized controlled pilot trial. In: Addiction. 2017.
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abstract = "Background and aims: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance and tolerability were evaluated. Design: Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC). Setting: Single-site out-patient treatment research clinic in Houston, TX, USA. Participants: Thirty treatment-seeking adults, 18 to 60 years old, with CUD. Eighteen participants (8 = PIO; 10 = PLC) completed diffusion tensor imaging (DTI) of WM integrity at pre-/post-treatment. Intervention: Study medication was dispensed at thrice weekly visits along with once-weekly cognitive behavioral therapy for 12 weeks. Measurements: Measures of target engagement mechanisms of interest included cocaine craving assessed by the Brief Substance Craving Scale (BSCS), the Obsessive Compulsive Drug Use Scale (OCDUS), a visual analog scale (VAS) and change in WM integrity. Feasibility measures included number completing treatment, medication compliance (riboflavin detection) and tolerability (side effects, serious adverse events). Findings: Target engagement change in mechanisms of interest, defined as a ≥ 0.75 Bayesian posterior probability of an interaction existing favoring PIO over PLC, was demonstrated on measures of craving (BSCS, VAS) and WM integrity indexed by fractional anisotropy (FA) values. Outcomes indicated greater decrease in craving and greater increase in FA values in the PIO group. Feasibility was demonstrated by high completion rates among those starting treatment (21/26 = 80{\%}) and medication compliance (≥ 80{\%}). There were no reported serious adverse events for PIO. Conclusions: Compared with placebo, patients receiving pioglitazone show a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in treatment. Pioglitazone shows good feasibility as a treatment for cocaine use disorder.",
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T1 - PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder

T2 - A double-blind randomized controlled pilot trial

AU - Schmitz, Joy M.

AU - Green, Charles E.

AU - Hasan, Khader M.

AU - Vincent, Jessica

AU - Suchting, Robert

AU - Weaver, Michael F.

AU - Moeller, F. Gerard

AU - Narayana, Ponnada A.

AU - Cunningham, Kathryn

AU - Dineley, Kelly

AU - Lane, Scott D.

PY - 2017

Y1 - 2017

N2 - Background and aims: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance and tolerability were evaluated. Design: Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC). Setting: Single-site out-patient treatment research clinic in Houston, TX, USA. Participants: Thirty treatment-seeking adults, 18 to 60 years old, with CUD. Eighteen participants (8 = PIO; 10 = PLC) completed diffusion tensor imaging (DTI) of WM integrity at pre-/post-treatment. Intervention: Study medication was dispensed at thrice weekly visits along with once-weekly cognitive behavioral therapy for 12 weeks. Measurements: Measures of target engagement mechanisms of interest included cocaine craving assessed by the Brief Substance Craving Scale (BSCS), the Obsessive Compulsive Drug Use Scale (OCDUS), a visual analog scale (VAS) and change in WM integrity. Feasibility measures included number completing treatment, medication compliance (riboflavin detection) and tolerability (side effects, serious adverse events). Findings: Target engagement change in mechanisms of interest, defined as a ≥ 0.75 Bayesian posterior probability of an interaction existing favoring PIO over PLC, was demonstrated on measures of craving (BSCS, VAS) and WM integrity indexed by fractional anisotropy (FA) values. Outcomes indicated greater decrease in craving and greater increase in FA values in the PIO group. Feasibility was demonstrated by high completion rates among those starting treatment (21/26 = 80%) and medication compliance (≥ 80%). There were no reported serious adverse events for PIO. Conclusions: Compared with placebo, patients receiving pioglitazone show a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in treatment. Pioglitazone shows good feasibility as a treatment for cocaine use disorder.

AB - Background and aims: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance and tolerability were evaluated. Design: Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC). Setting: Single-site out-patient treatment research clinic in Houston, TX, USA. Participants: Thirty treatment-seeking adults, 18 to 60 years old, with CUD. Eighteen participants (8 = PIO; 10 = PLC) completed diffusion tensor imaging (DTI) of WM integrity at pre-/post-treatment. Intervention: Study medication was dispensed at thrice weekly visits along with once-weekly cognitive behavioral therapy for 12 weeks. Measurements: Measures of target engagement mechanisms of interest included cocaine craving assessed by the Brief Substance Craving Scale (BSCS), the Obsessive Compulsive Drug Use Scale (OCDUS), a visual analog scale (VAS) and change in WM integrity. Feasibility measures included number completing treatment, medication compliance (riboflavin detection) and tolerability (side effects, serious adverse events). Findings: Target engagement change in mechanisms of interest, defined as a ≥ 0.75 Bayesian posterior probability of an interaction existing favoring PIO over PLC, was demonstrated on measures of craving (BSCS, VAS) and WM integrity indexed by fractional anisotropy (FA) values. Outcomes indicated greater decrease in craving and greater increase in FA values in the PIO group. Feasibility was demonstrated by high completion rates among those starting treatment (21/26 = 80%) and medication compliance (≥ 80%). There were no reported serious adverse events for PIO. Conclusions: Compared with placebo, patients receiving pioglitazone show a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in treatment. Pioglitazone shows good feasibility as a treatment for cocaine use disorder.

KW - Bayesian statistics

KW - Cocaine use disorder

KW - Craving

KW - Pioglitazone

KW - PPAR-gamma

KW - Target engagement

KW - White matter integrity

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