Brain Imaging Study of the Effects of Modafinil in Cocaine Addiction

Phase 3

Completed

• Conditions: Cocaine Addiction; Cocaine Dependence
• Interventions: Drug: Modafinil and PET (brain imaging); Drug: placebo

• Registration Number: NCT00701532
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief 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.

Study Timeline

• Study First Submitted: 2008-06-18
• Study First Submitted QC: 2008-06-18
• Study First Posted: 2008-06-19
• Study Start: 2009-04
• Primary Completion: 2012-10
• Study Completion: 2013-01
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-10
• Last Update Posted: 2013-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 29

Inclusion Criteria

• Men of at least 18 years of age
• Cocaine dependent according to DSM IV TR criteria
• Seeking treatment
• Capable of understanding and giving their informed written consent
• With National Health coverage
• Urinary screen positive for cocaine in the weeks prior to inclusion

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Exclusion Criteria

• Women
• Other DSM IV TR axe I diagnostic criteria (except for tobacco)
• Neurological disorders
• Treatment that interferes with the DAT and modafinil
• Contraindications for modafinil and Magnetic Resonance Imaging

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Modafinil and PET (brain imaging)	active
2	placebo	Placebo

Primary Outcome Measures

Name	Time	Method
Decreased DAT occupation rates in the modafinil group versus placebo from day 3 to day of cocaine detoxification.	day 3 and day of cocaine detoxification

Secondary Outcome Measures

Name	Time	Method
Evaluation of the clinical efficacy of modafinil during therapeutic cocaine withdrawal.	D3 to D90
Correlation between craving measurements, depressive symptom measurements and cognitive deficit measurements observed and modifications of DAT density.	D3 to D21
Study of DAT from D3 to D21 versus a pre-existing data base of control subjects.	D3 to D21
Tolerance and safety evaluation of high modafinil doses, measured by adverse events and biological parameters.	D3 to D90

Trial Locations

Locations (2)

Centre d'Enseignement, de Recherche et de Traitements des Addictions - Hopital Universitaire Paul Brousse; 🇫🇷 Villejuif, France

Unité de recherche U797 Inserm - CEA - Université Paris-Sud. " Neuroimagerie & Psychiatrie " Service Hospitalier Frédéric Joliot; 🇫🇷 Orsay, France