Brain Imaging Study of the Effects of Modafinil in Cocaine Addiction

Cocaine Dependence Clinical Trial

— CAIMAN  

Official title:

Dopamine Transporter (DAT) in Pharmacological Treatments of Cocaine Dependence. CAIMAN (Cocaine Addiction Imaging Medications and Neurotransmitters) Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00701532
• Other study ID #: P070150
• Status: Completed
• Phase: Phase 3
• First received: June 18, 2008
• Last updated: April 10, 2013
• Start date: April 2009
• Est. completion date: January 2013

Study information

• Verified date: April 2013
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: January 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Behavior, Addictive
• Cocaine Addiction
• Cocaine Dependence
• Cocaine-Related Disorders

Intervention

Drug:
• Modafinil and PET (brain imaging)
duration 90 days
• placebo
duration 90 days

Locations

Country	Name	City	State
France	Unité de recherche U797 Inserm - CEA - Université Paris-Sud. " Neuroimagerie & Psychiatrie " Service Hospitalier Frédéric Joliot	Orsay
France	Centre d'Enseignement, de Recherche et de Traitements des Addictions - Hopital Universitaire Paul Brousse	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Mission Interministérielle de Lutte contre la Drogue et la Toxicomanie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Evaluation of the clinical efficacy of modafinil during therapeutic cocaine withdrawal.		D3 to D90	No
Secondary	Correlation between craving measurements, depressive symptom measurements and cognitive deficit measurements observed and modifications of DAT density.		D3 to D21	No
Secondary	Study of DAT from D3 to D21 versus a pre-existing data base of control subjects.		D3 to D21	No
Secondary	Tolerance and safety evaluation of high modafinil doses, measured by adverse events and biological parameters.		D3 to D90	Yes