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.

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 an...

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Publicado en:Addiction Vol. 112; no. 10; pp. 1861 - 1869
Autores principales: Schmitz, Joy M., Green, Charles E., Hasan, Khader M., Vincent, Jessica, Suchting, Robert, Weaver, Michael F., Moeller, F. Gerard, Narayana, Ponnada A., Cunningham, Kathryn A., Dineley, Kelly T., Lane, Scott D.
Formato: research tables/charts randomized controlled trial Journal Article
Publicado: Wiley-Blackwell Oct2017
Acceso en línea:Ver este registro en EBSCOhost
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      pub: Wiley-Blackwell
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        atl: 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.
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        au:
          Schmitz, Joy M.
          Green, Charles E.
          Hasan, Khader M.
          Vincent, Jessica
          Suchting, Robert
          Weaver, Michael F.
          Moeller, F. Gerard
          Narayana, Ponnada A.
          Cunningham, Kathryn A.
          Dineley, Kelly T.
          Lane, Scott D.
        affil: McGovern Medical School, University of Texas Health Science Center at Houston, Houston TX, USA
      sug:
        subj:
          PPAR-gamma Agonists
          Pioglitazone Administration and Dosage
          Craving Drug Effects
          Brain
          Cocaine
          Substance Dependence Drug Therapy
          Human
          Randomized Controlled Trials
          Double-Blind Studies
          Pilot Studies
          Medication Compliance
          Texas
          Adolescence
          Adult
          Middle Age
          Pretest-Posttest Design
          Substance Dependence Therapy
          Cognitive Therapy
          Visual Analog Scaling
          Riboflavin Analysis
          Pioglitazone Adverse Effects
          Descriptive Statistics
          Placebos Administration and Dosage
          Scales
          Adolescent: 13-18 years
          Adult: 19-44 years
          Middle Aged: 45-64 years
      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.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        randomized controlled trial
        Journal Article
      ougenre: Article
    language: English
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