Brain Imaging Study of the Effects of Modafinil in Cocaine Addiction
Condition: Cocaine Addiction; Cocaine Dependence
MeSH terms: Cocaine-Related Disorders; Behavior, Addictive
Study type: Interventional
Phase: Phase 3

Summary: 
      -Context: Study objectives Primary: impact of modafinil versus placebo on DAT density
      modifications in the striatal and extra-striatal regions in cocaine dependent subjects
      hospitalised from D3 to D21.

      Primary Hypothesis:

      More rapid normalisation of DAT concentrations measured by PET using modafinil versus placebo
      from D3 to D21 during cocaine detoxification.
    

Detailed description: 
      Context:

      Cocaine dependence is a disorder with a rapidly progressive evolution, associated with
      various complications. Because of cocaine's direct action on the dopamine transporter (DAT),
      dopaminergic system dysregulation plays a fundamental role in reinforcement phenomenon and in
      dependence. This has been proven in numerous animal and post-death human studies of striatal
      DAT. In vivo studies in cocaine dependent patients are rare. Currently no pharmacotherapy is
      available to treat this pathology. Current studies indicate that pharmacological agents such
      as modafinil may be able to reverse the neuroadaptations induced by cocaine dependence.
      However, no functional neuroimaging study (Positron Emission Tomography, PET) has analysed
      the impact of medications on DAT density in cocaine dependent patients. However, in primates,
      in vivo PET has shown modafinil affinity for DAT.

      Primary Hypothesis:

      More rapid normalisation of DAT concentrations measured by PET using modafinil versus placebo
      from D3 to D21 during therapeutic cocaine withdrawal.

      Study objectives Primary: impact of modafinil versus placebo on DAT density modifications in
      the striatal and extra-striatal regions in cocaine dependent subjects hospitalised from D3 to
      D21.

      Secondary:

      Evaluation of the clinical efficacy of modafinil during therapeutic cocaine withdrawal.
      Correlation between craving measurements, depressive symptom measurements and cognitive
      deficit measurements observed and modifications of DAT density.

      Study of DAT from D3 to D21 versus a pre-existing data base of control subjects.

      Tolerance and safety evaluation of high modafinil doses, measured by adverse events and
      biological parameters.

      Calculation of the number of subjects: A power of 90% is found for a number of subjects
      estimated at 24 (bilateral test, α risk at 5%, estimated SEM of 5%, variation of the
      occupational concentration of the DAT expected to be at least 12% in the modafinil group).
      Considering the usual rate of patients lost to follow-up in this patient population (25%), we
      plan to include 30 patients.

      Methodology: This study is regulated by the law on biomedical research of August 9, 2004. It
      is a randomised monocentric double blind study versus placebo. During the study, for 90 days,
      patients will receive in double blind either modafinil or placebo according to their
      randomisation arm.

      Evaluations will include 2 PET, cerebral MRI, blood work-up, urinary toxin screen, clinical
      scales for craving, depression and neuropsychological evaluations.

      Patients will be recruited over 24 months. The total study length will be 36 months.

      Primary judgment criteria: Variation of the linking potentials (specific fixation rate for
      the radioligand [11C]-PE2I to DAT) between the TEP measurement on D3 and D21 within the
      various anatomical region of interest between the 2 groups (modafinil, placebo).

      Expected Results: Decreased DAT occupation rates in the modafinil group versus placebo from
      D3 to D21 of withdrawal.
    

Intervention name(s): Modafinil and PET (brain imaging); placebo
Intervention type(s): Drug; Drug
Intervention description(s): duration 90 days; duration 90 days
Intervention MeSH terms: Modafinil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cocaine; Substance abuse; Addiction; Dependence; Modafinil; Brain imaging