Cocaine Dependence
Conditions
Keywords
cocaine, dependence, risperidal, MRI
Brief summary
The purpose of this study is to examine the effects of the administration of Risperidal-Consta on the brain's reward circuitry using Magnetic resonance Imaging (MRI), behavioral tests and measuring cocaine craving and use among people with active cocaine dependence.
Interventions
DRUGRisperidone
DRUGPlacebo
Sponsors
Janssen, LP
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* current cocaine dependence who use cocaine at least every 2 weeks * Non-treatment seekers who intend to continue using cocaine * Male 18-60 years of age * Potential participants must be literate in the English language, and be able to understand and complete rating scales and questionnaires accurately * Able to provide informed consent * Potential participants must be able to identify at least one locator person to assist in tracking the participant for follow-up assessments
Exclusion criteria
* Other current substance dependence requiring immediate detoxification * Diagnosis of schizophrenia, bipolar disorder, current major depressive disorder * Currently suicidal or at high risk for suicide in the judgment of the investigator * Carrying a medical device incompatible with MRI (e.g., metal implants such as surgical clips or pacemakers and extensive dental work such as bridges) or suffering from significant claustrophobia that would make MRI unfeasible. * Size incompatible with MRI procedures * Serious medical illness including HIV-1 infection * Hepatitis C + titer with liver enzymes more than 2x normal or a Mini-Mental Status Exam Score of \<25/30 * Insulin dependent diabetes mellitus (IDDM) or non- insulin dependent diabetes mellitus (NIDDM) and abnormal Hemoglobin A1C * Severe hepatic or renal impairment * History of seizure disorder, delirium, dementia, or mental disorders due to general medical conditions * History of head trauma or stroke with lasting neurological sequelae * Tardive dyskinesia, extrapyramidal movement disorder, Parkinson's Disease or history of Neuroleptic Malignant Syndrome * Clinical or laboratory evidence of uncontrolled hypothyroidism/hyperthyroidism * Orthostatic hypotension, defined as a decrease of at \> 10 mm Hg in systolic blood pressure and/or an increase in heart rate of \> 20 beats per minute, measured one minute following transition from a supine to a standing position. * History of allergy or hypersensitivity to Risperidone * Treatment with: Neuroleptics, Antidepressants, Antiarrhythmics, Carbamazepine, Phenytoin, Valproate, Rifampin, Phenobarbital, Levodopa and other dopamine agonists, Fluoxetine, Interferon, Propylthiouracil, Methimazole, Opiates. * Treatment within 30 days prior to screening with an investigational drug or medication with the potential to influence cocaine use outcomes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional MRI Activation Patterns in the Nucleus Accumbens and Amygdala in Response to Cocaine Cues | 12 weeks | Measure of Dispersion/Precision not calculated, and raw data are no longer available |
| Cocaine Use by Quantitative Urine Samples | 12 weeks | After randomization, participants provided urine samples every week for the first 3 weeks and then every 2 weeks for 8 weeks, up to 7 samples per participant. The average visits with cocaine negative urine samples per participant are reported below |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Craving | 12 weeks | The University of Minnesota Cocaine Craving Scale was performed to assess cocaine craving. The scale contains 1 continuous scale for intensity and 2 categorical scales for frequency and duration of craving episodes. The continuous scale for craving intensity ranges from 0 (no craving at all in the past week) to 10 (a great deal of craving in the past week) |
| Amygdala Volume by MRI | 12 weeks | Measure of Dispersion/Precision not calculated, and raw data are no longer available |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from October 2005 to September 2006 via advertisement in local press
Pre-assignment details
After baseline evaluation participants began treatment with oral risperidone, 1 mg per day the first week and 2 mg per day for the next 3 weeks. Electrocardiograms were repeated after 1 and 2 weeks of risperidone use. Participants with corrected QT interval (QTc) prolongation greater than 470 milliseconds at either of these occasions were excluded
Participants by arm
| Arm | Count |
|---|---|
| Placebo Identical placebo tablets and injections | 15 |
| Risperidone Consta Risperidone 1-2 mg tablets and Risperidone 25 mg injections | 16 |
| Total | 31 |
Baseline characteristics
| Characteristic | Risperidone Consta | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 44.1 years STANDARD_DEVIATION 5.9 | 43 years STANDARD_DEVIATION 6.1 | 42.4 years STANDARD_DEVIATION 6.4 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 31 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 15 | 13 / 16 |
| serious Total, serious adverse events | 0 / 15 | 0 / 16 |
Outcome results
Primary
Cocaine Use by Quantitative Urine Samples
After randomization, participants provided urine samples every week for the first 3 weeks and then every 2 weeks for 8 weeks, up to 7 samples per participant. The average visits with cocaine negative urine samples per participant are reported below
Time frame: 12 weeks
Population: Mean number of visits at which participants submitted urine samples with undetectable urine benzoylecgonine (UBE)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cocaine Use by Quantitative Urine Samples | 1.81 visit with negative UBE | Standard Deviation 2.29 |
| Risperidone Consta | Cocaine Use by Quantitative Urine Samples | 0.87 visit with negative UBE | Standard Deviation 1.8 |
Primary
Functional MRI Activation Patterns in the Nucleus Accumbens and Amygdala in Response to Cocaine Cues
Measure of Dispersion/Precision not calculated, and raw data are no longer available
Time frame: 12 weeks
Population: Measure of Dispersion/Precision not calculated, and raw data are no longer available
Secondary
Amygdala Volume by MRI
Measure of Dispersion/Precision not calculated, and raw data are no longer available
Time frame: 12 weeks
Population: Measure of Dispersion/Precision not calculated, and raw data are no longer available
Secondary
Cocaine Craving
The University of Minnesota Cocaine Craving Scale was performed to assess cocaine craving. The scale contains 1 continuous scale for intensity and 2 categorical scales for frequency and duration of craving episodes. The continuous scale for craving intensity ranges from 0 (no craving at all in the past week) to 10 (a great deal of craving in the past week)
Time frame: 12 weeks
Population: Mixed model repeated measures analysis of variance was performed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Cocaine Craving | NA units on a scale |
| Risperidone Consta | Cocaine Craving | NA units on a scale |
Comparison: Intensity of cravingp-value: 0.86Mixed Models Analysis