Cocaine Dependence
Conditions
Keywords
drug abuse, cocaine, impulsivity, dopamine
Brief summary
This project proposes to investigate the role of brain connectivity in the mechanism of treatment response to dopaminergic medications in cocaine dependence.
Detailed description
This project will use stochastic DCM, which is a recent DCM extension that takes into account hidden fluctuations in neuronal and vascular responses, and thus is especially suited for investigating effects of disease or drugs. In addition, this project will use nonlinear DCM, a DCM extension that can measure gating effects by striatum on cortico-cortical pathways. The overall aims of this project are: (1) To conduct functional magnetic resonance imaging-based DCM studies of working memory and impulsivity in order to determine the effective (directional) connectivity between PFC and striatum in treatment-seeking Cocaine Dependent (CD) subjects compared to non-drug using controls. We hypothesize that DLPFC causally affects ventral striatum in CDs, and that the strength of this connection is lower in CDs compared to controls. (2) To determine whether the pretreatment gating effect by the dorsal striatum, as a reflection of pretreatment hypodopaminergic state associated with chronic compulsive drug use, predicts the treatment response to dopaminergic pharmacotherapy in CDs. We hypothesize that lower pretreatment gating by the dorsal striatum on prefrontal-parietal effective connectivity predicts greater 8-week improvement from treatment of CDs with DA enhancing medications (combined with cognitive behavioral therapy \[CBT\]), but not from treatment with placebo (combined with CBT).
Interventions
DRUGlevodopa/carbidopa 400/100 BID
Levodopa dose escalation (1 week): Days 1-2, one 50/12.5 mg tablet BID; Days 3-4, one 100/25 mg tablet BID; Days 5-6, one 200/50 mg tablet BID; Day 7, one 400/100 mg tablet BID. Maintenance phase (7 weeks): One 400/100 mg Levodopa/Carbidopa tablet BID or placebo in conjunction with once weekly individual cognitive behavioral therapy plus contingency management for attendance.
Sponsors
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
Yes
Inclusion criteria
* Male and female subjects * Age 18 to 50 * 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 levodopa/carbidopa or pharmacotherapy (e.g., evidence of any movement disorder, clinically significant pulmonary disease, cardiovascular disease, liver or kidney disease, seizure disorder) 5. Taking CNS active concomitant medications 6. Taking medications known to have significant drug interactions with the study medication (e.g., CYP P-450-2D6 inhibitors, such as tamoxifen, iron salts, pyridoxine, monoamine oxidase inhibitors, phenothiazines, selegiline, anesthetics) 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 Treatment Outcome | Baseline to 12 weeks | Treatment effectiveness score based on number of positive urine drug screens |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Control Non drug using healthy controls | 38 |
| Placebo Placebo BID for 7 weeks
levodopa/carbidopa 400/100 BID: Levodopa dose escalation (1 week): Days 1-2, one 50/12.5 mg tablet BID; Days 3-4, one 100/25 mg tablet BID; Days 5-6, one 200/50 mg tablet BID; Day 7, one 400/100 mg tablet BID.
Maintenance phase (7 weeks): One 400/100 mg Levodopa/Carbidopa tablet BID or placebo in conjunction with once weekly individual cognitive behavioral therapy plus contingency management for attendance. | 9 |
| Medication Levodopa/carbidopa 400/100 BID for 7 weeks
levodopa/carbidopa 400/100 BID: Levodopa dose escalation (1 week): Days 1-2, one 50/12.5 mg tablet BID; Days 3-4, one 100/25 mg tablet BID; Days 5-6, one 200/50 mg tablet BID; Day 7, one 400/100 mg tablet BID.
Maintenance phase (7 weeks): One 400/100 mg Levodopa/Carbidopa tablet BID or placebo in conjunction with once weekly individual cognitive behavioral therapy plus contingency management for attendance. | 11 |
| Total | 58 |
Baseline characteristics
| Characteristic | Placebo | Medication | Total | Healthy Control |
|---|---|---|---|---|
| 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 | 9 Participants | 11 Participants | 58 Participants | 38 Participants |
| Age, Continuous | 33 years STANDARD_DEVIATION 7 | 35 years STANDARD_DEVIATION 8 | 33 years STANDARD_DEVIATION 12 | 30 years STANDARD_DEVIATION 12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 10 Participants | 40 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 10 Participants | 9 Participants |
| Region of Enrollment United States | 9 participants | 11 participants | 30 participants | 38 participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 24 Participants | 19 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 34 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 9 | 0 / 11 |
| other Total, other adverse events | 0 / 38 | 0 / 9 | 0 / 11 |
| serious Total, serious adverse events | 0 / 38 | 0 / 9 | 0 / 11 |
Outcome results
Primary
Cocaine Treatment Outcome
Treatment effectiveness score based on number of positive urine drug screens
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Control | Cocaine Treatment Outcome | 0 positive drug screens | Standard Deviation 0 |
| Placebo | Cocaine Treatment Outcome | 14 positive drug screens | Standard Deviation 15 |
| Medication | Cocaine Treatment Outcome | 13 positive drug screens | Standard Deviation 9 |