Cocaine Dependence
Conditions
Keywords
substance abuse, cocaine, impulsivity, serotonin, MRI
Brief summary
The purpose of this study is to examine the role of brain MRI findings in predicting treatment outcomes among individuals with cocaine dependence.
Detailed description
The Specific Aims of this project are: Aim 1: To determine whether pretreatment brain activation on fMRI while performing a Go-Nogo task predicts response to pharmacotherapy in cocaine dependent subjects. Hypothesis related to Aim 1: Pretreatment fMRI BOLD activation in cocaine dependent subjects during impulsive responding on the Go-Nogo task predicts 8-week outcome from medication known to enhance serotonin function (citalopram). The regression coefficient of TES on pretreatment mean BOLD activation on the Go-Nogo task will be significantly greater for the citalopram group than the placebo group. Aim 2: To determine whether pretreatment brain activation on fMRI while performing an attentional bias (cocaine Stroop) task predicts response to pharmacotherapy in cocaine dependent subjects. Hypothesis related to Aim 2: Pretreatment fMRI BOLD activation in cocaine dependent subjects during cocaine related words on the cocaine Stroop task predicts 8-week outcome from medication known to enhance serotonin function (citalopram). The regression coefficient of TES on pretreatment mean BOLD activation from the cocaine Stroop task will be significantly greater for the citalopram group than the placebo group.
Interventions
DRUGCitalopram
20 mg or 40 mg daily for 8 weeks
DRUGPlacebo
Placebo daily for 8 weeks
Sponsors
The University of Texas Health Science Center, Houston
National Institute on Drug Abuse (NIDA)
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects age 18 to 50 who meet current DSM-IV criteria for cocaine dependence who are seeking treatment.
Exclusion criteria
1. Current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, marijuana, nicotine, or alcohol 2. Have a DSM-IV axis I psychiatric disorder or neurological disease or disorder requiring ongoing treatment and/or making study participation unsafe 3. Significant current suicidal or homicidal ideation 4. Medical conditions contraindicating citalopram pharmacotherapy (liver disease, seizure disorder, bleeding disorder, or prolonged QT interval on EKG) 5. Taking CNS active concomitant medications 6. Taking medications known to have significant drug interactions with the study medication 7. Having conditions of probation or parole requiring reports of drug use to officers of the court 8. Impending incarceration 9. Pregnant or breast feeding for female patients 10. Inability to read, write, or speak English 11. Having plans to leave the immediate geographical area within 3 months 12. Unwillingness or not competent to sign a written informed consent form 13. Individuals who have pacemakers, metal or electromechanical implants or metallic foreign bodies 14. Patients who are known to be HIV positive will not be included due to possible CNS effects of HIV. 15. Alcohol withdrawal symptoms or history of significant previous alcohol withdrawal symptoms.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Use/Treatment Effectiveness Score (TES) | 8 weeks of treatment | Number of benzoylecgonine negative urines divided by the total number of urines collected |
Other
| Measure | Time frame | Description |
|---|---|---|
| fMRI Brain Activation in Right Inferior Frontal Gyrus | Baseline | Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score. |
| fMRI Brain Activation in Right Precentral Gyrus | Baseline | Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score. |
| fMRI Brain Activation in Right Orlandic Operculum | Baseline | Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score. |
Countries
United States
Participant flow
Pre-assignment details
For some consented participants, the imaging scan (MRI) quality was not sufficient to include those participants in the outcome analysis. These participants are captured by theexcluded from analysis by MRI category. fMRI data was only analyzed from participants who underwent MRI scans at UT Houston which can't be combined with MRI scans at VCU.
Participants by arm
| Arm | Count |
|---|---|
| Medication Citalopram 20mg Citalopram (20mg dose)
Citalopram: 20 mg daily for 8 weeks | 15 |
| Placebo Placebo: Placebo daily for 8 weeks | 17 |
| Medication Citalopram 40mg Citalopram (40mg dose) 40mg daily for 8 weeks | 22 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Excluded from analysis by MRI | 9 | 10 | 14 |
| Overall Study | Lost to Follow-up | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Medication Citalopram 20mg | Placebo | Medication Citalopram 40mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 17 Participants | 22 Participants | 54 Participants |
| Race/Ethnicity, Customized African American | 12 Participants | 13 Participants | 18 Participants | 43 Participants |
| Race/Ethnicity, Customized Caucasian | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 15 participants | 17 participants | 22 participants | 54 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 17 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 5 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 | 0 / 6 |
Outcome results
Primary
Cocaine Use/Treatment Effectiveness Score (TES)
Number of benzoylecgonine negative urines divided by the total number of urines collected
Time frame: 8 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medication (Citalopram 20mg) | Cocaine Use/Treatment Effectiveness Score (TES) | 6.6 percentage of negative urines |
| Placebo | Cocaine Use/Treatment Effectiveness Score (TES) | 8.3 percentage of negative urines |
| Medication (Citalopram 40mg) | Cocaine Use/Treatment Effectiveness Score (TES) | 29 percentage of negative urines |
Other Pre-specified
fMRI Brain Activation in Right Inferior Frontal Gyrus
Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score.
Time frame: Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medication (Citalopram 20mg) | fMRI Brain Activation in Right Inferior Frontal Gyrus | 83 Percent of significant voxels in cluster |
| Placebo | fMRI Brain Activation in Right Inferior Frontal Gyrus | 0 Percent of significant voxels in cluster |
Other Pre-specified
fMRI Brain Activation in Right Orlandic Operculum
Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score.
Time frame: Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medication (Citalopram 20mg) | fMRI Brain Activation in Right Orlandic Operculum | 8 percent of significant voxels in cluster |
| Placebo | fMRI Brain Activation in Right Orlandic Operculum | 0 percent of significant voxels in cluster |
Other Pre-specified
fMRI Brain Activation in Right Precentral Gyrus
Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score.
Time frame: Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medication (Citalopram 20mg) | fMRI Brain Activation in Right Precentral Gyrus | 9 percent of significant voxels in cluster |
| Placebo | fMRI Brain Activation in Right Precentral Gyrus | 0 percent of significant voxels in cluster |