The Effects of Pharmacotherapy on Brain Mechanisms Underlying Cocaine Dependence. - Full Text View

Purpose

The overall aim of this project is to use an advanced brain imaging technique, PET, in order to monitor the progress of pharmacotherapy with modafinil or topiramate for cocaine dependence in methadone-maintained patients who use cocaine in addition. Comparisons will be made within the cocaine dependent methadone maintained subjects, between the start and end of treatment, and between the two medications. This is the first systematic research study of pharmacological treatment for cocaine dependence in Israel. This study is of major clinical use, with implications for the treatment of cocaine dependence in poly-drug abusers in Israel. Successful pharmacotherapy for cocaine dependence is expected in reduction in cue-induced subjective craving and in glucose metabolism in brain areas elicited by cocaine craving. Metabolic activity in regions that are activated by craving should be correlated with dopamine DRD2 receptor occupancy in all patients.

Condition	Intervention
Opioid-Related Disorders Cocaine-Related Disorders	Drug: Provigil (Modafinil) Drug: Topamax (Topiramate)

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	The Effects of Modafinil and Topiramate on Brain Mechanisms Underlying Cue-induced Cocaine Craving and Dependence in Methadone Maintained Cocaine Dependent Patients.

Resource links provided by NLM:

Drug Information available for: Cocaine hydrochloride Methadone Methadone hydrochloride Modafinil Topiramate Armodafinil

U.S. FDA Resources

Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:

Changes in cue-induced brain glucose metabolic activity (FDG) in PET after treatment. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
Changes in DRD2 receptor density measured by 11 C Raclopride in PET after treatment. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
Nr.of drug-free urine samples, time to first drug use, duration of longest abstinent period. [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Craving and psychosocial functioning (e.g., employment status, criminal behavior). [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	April 2007
Estimated Study Completion Date:	April 2011
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Intervention Details:

Increase from 100mg to 400mg during 1 month of treatment

Increase from 25mg to 200mg in one month (double every week)

Detailed Description:

SPECIFIC AIMS

To try to elucidate the brain mechanisms underlying cocaine dependence and craving in co-morbid cocaine-dependent patients. For this purpose we shall trigger craving for cocaine by exposure to a videotape showing cocaine use and then measure brain metabolic activity using Positron Emission Tomography (PET) and [18F] Fluorodeoxyglucose (FDG)
To evaluate dopamine binding in the brain in the early stage, and at the end of treatment. For this purpose the patients will undergo brain imaging of the dopamine receptor DRD2 by using PET with [11C] raclopride. This is a well established procedure for quantifying the effects of drugs such as amphetamine and cocaine on the brain.
To investigate the association between subjective measures of craving for cocaine and the level of dopamine DRD2 receptor occupancy in the brain.

Eligibility

Ages Eligible for Study:	20 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Methadone-maintained cocaine-dependent patients use between 1g to 2g a day; 1 to 3 times a week

Exclusion Criteria:

use more than 2g a day; 5 times a week to everyday
Subjects who are diagnosed as suffering from psychotic illness according to DSM-IV (Axis 1)22, or with a history of CNS disease, a history of infection that might affect CNS (HIV, syphilis, cytomegalovirus, herpes), or a history of head injury with loss of consciousness,pregnant women.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00396734

Locations

Israel
Hadassah Medical Organization
Jerusalem, Israel, 91120

Sponsors and Collaborators

Hadassah Medical Organization

Investigators

Study Director:	Aviv M Weinstein, Ph.D	Hadassah Medical Organization
Principal Investigator:	Roland Chisin, M.D	Hadassah Medical Organization

More Information

No publications provided

Responsible Party:	Dr Arik Zukert, Hadassah Medical Organization
ClinicalTrials.gov Identifier:	NCT00396734 History of Changes
Other Study ID Numbers:	281006-HMO-CTIL
Study First Received:	November 6, 2006
Last Updated:	June 9, 2010
Health Authority:	Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Hadassah Medical Organization:

Imaging
cocaine
methadone
craving
PET

FDG
D2
Modafinil
Topiramate

Additional relevant MeSH terms:

Opioid-Related Disorders
Cocaine-Related Disorders
Substance-Related Disorders
Mental Disorders
Cocaine
Methadone
Modafinil
Topiramate
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents

Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Opioid
Analgesics
Antitussive Agents
Respiratory System Agents
Narcotics
Central Nervous System Stimulants

ClinicalTrials.gov processed this record on June 17, 2013