Cocaine Dependence
Conditions
Keywords
Cocaine, Methadone, CBT
Brief summary
We are testing to see if Galantamine, a learning enhancing medication, will help methadone maintained cocaine abusers with their learning and memory specific to CBT using an innovative CBT computer program.
Detailed description
We are proposing a randomized double blind clinical trial of galantamine and our innovative computer-assisted version of CBT, alone and in combination, to improve treatment outcome and cognitive functioning among cocaine users. The proposed study will be the first to evaluate a cognitive enhancing medication as a means of enhancing the effects of an extremely promising empirically validated behavioral therapy for addiction, and hence bridge cognitive neuroscience and behavioral therapies development. The aim is to conduct a 12 week randomized placebo controlled trial, using a 2x2 factorial model, that will evaluate the efficacy of adding computer assisted training in CBT (CBT4CBT) and galantamine to standard treatment for 160 cocaine abusing or dependent methadone-maintained individuals. Participants will be randomized to (1) standard treatment (TAU) plus placebo, (2) TAU plus galantamine, (3) TAU plus CBT4CBT plus placebo, or (4) TAU plus CBT4CBT plus galantamine.
Interventions
DRUGGalantamine
Daily 8 mg galantamine capsule
BEHAVIORALComputer Assisted Cognitive Behavioral Therapy (CBT)
CBT a psychotherapeutic approach that addresses dysfunctional emotions, maladaptive behaviors and cognitive processes and contents through a number of goal-oriented, explicit systematic procedures. The name refers to behavior therapy, cognitive therapy, and to therapy based upon a combination of basic behavioral and cognitive principles and research.
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Males and females between ages of 18 and 50 * Enrolled in RNP methadone program and stable on methadone for at least 3 weeks * Current cocaine abuse or dependence according to DSM-IV criteria * No current medical problems and normal ECG * If female, not currently pregnant or breast feeding and using reliable birth control * Fluent in English and have at least a 6th grade reading level * Can commit to 12 weeks of treatment and are willing to be randomized
Exclusion criteria
* Current major psychiatric illness including mood, psychotic or anxiety disorder * History of major medical illnesses including asthma, chronic obstructive lung disease, gastrointestinal ulcer, hepatic or renal impairment, cardiac rhythm disturbances * Use of medications including beta blockers and NASAIDs * Known allergy to Galantamine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Use | 12 weeks | Reduction in cocaine use, operationalized as the frequency of cocaine use by month using timeline followback. |
| Cocaine Abstinence | 12 weeks | operationalized by percentage of drug-free urine specimens submitted (We will use the Branan ToxCup Drug Screen Cup onsite TESTCUP system for detection of cocaine, methamphetamine, THC, benzodiazepine, and opioids) at 12 Weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Function | 12 weeks | A composite using a carefully selected neuropsychological battery that includes measures of executive cognitive functioning frequently affected among cocaine users, likely to be important moderators of CBT4CBT, and sensitive to galantamine effects. These will include measures of multiple aspects of attention, cognitive inhibition, sustained attention (CANTAB), decision making (BART), and memory (digit span). Scores ranged from -1.77 to 1.42 with a higher score indicating higher cognitive functioning. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Galantamine and CBT Drug: Galantamine Daily 8 mg galantamine capsule
Other Names:
Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine
Behavioral: Computer Assisted Cognitive Behavioral Therapy (CBT) CBT a psychotherapeutic approach that addresses dysfunctional emotions, maladaptive behaviors and cognitive processes and contents through a number of goal-oriented, explicit systematic procedures. The name refers to behavior therapy, cognitive therapy, and to therapy based upon a combination of basic behavioral and cognitive principles and research. | 28 |
| Galantamine Drug: Galantamine Daily 8 mg galantamine capsule
Other Names:
Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine | 27 |
| Placebo and CBT Computer assisted CBT plus placebo. All participants assigned to this condition will also be offered up to 60 minutes per week to work with the CBT for CBT program, onsite at the clinic, in a private space and using a computer provided by the research project. Patients will have the choice of how they choose to use the computer, that is, in two 30-minute sessions or one one-hour session. | 38 |
| Placebo Only Standard Treatment plus placebo for cocaine abusing or dependent methadone-maintained individuals. This consists of daily methadone visits plus one individual and one group session per week, and patients may participate in additional treatments such as HIV education and treatment. The counseling program's theoretical orientation is described as client-centered. | 27 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 6 | 10 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Galantamine and CBT | Galantamine | Placebo and CBT | Placebo Only | Total |
|---|---|---|---|---|---|
| Age, Continuous | 38.04 years STANDARD_DEVIATION 8.72 | 38.70 years STANDARD_DEVIATION 10.79 | 39.82 years STANDARD_DEVIATION 8.99 | 36.30 years STANDARD_DEVIATION 9.41 | 38.36 years STANDARD_DEVIATION 9.43 |
| Race/Ethnicity, Customized African-American | 7 participants | 6 participants | 9 participants | 3 participants | 25 participants |
| Race/Ethnicity, Customized Caucasian | 12 participants | 15 participants | 19 participants | 16 participants | 62 participants |
| Race/Ethnicity, Customized Hispanic | 9 participants | 6 participants | 9 participants | 8 participants | 32 participants |
| Race/Ethnicity, Customized Multiracial/Other | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 12 Participants | 15 Participants | 19 Participants | 16 Participants | 62 Participants |
| Sex: Female, Male Male | 16 Participants | 12 Participants | 19 Participants | 11 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 28 | 10 / 27 | 16 / 38 | 14 / 27 |
| serious Total, serious adverse events | 4 / 28 | 6 / 27 | 6 / 38 | 5 / 27 |
Outcome results
Primary
Cocaine Abstinence
operationalized by percentage of drug-free urine specimens submitted (We will use the Branan ToxCup Drug Screen Cup onsite TESTCUP system for detection of cocaine, methamphetamine, THC, benzodiazepine, and opioids) at 12 Weeks
Time frame: 12 weeks
Population: Three arm had one subject drop out before study medication was given- therefore the number analyzed are those that received first treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine and CBT | Cocaine Abstinence | 22.45 percentage of negative urines | Standard Deviation 35.62 |
| Galantamine | Cocaine Abstinence | 31.13 percentage of negative urines | Standard Deviation 34.16 |
| Placebo and CBT | Cocaine Abstinence | 20.49 percentage of negative urines | Standard Deviation 27.6 |
| Placebo Only | Cocaine Abstinence | 14.78 percentage of negative urines | Standard Deviation 19.11 |
Primary
Cocaine Use
Reduction in cocaine use, operationalized as the frequency of cocaine use by month using timeline followback.
Time frame: 12 weeks
Population: Presented are data for those measured at baseline and at 12 weeks. 2 individuals in the Galantamine arm were not measured at 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Galantamine and CBT | Cocaine Use | 12 Weeks | 8.60 Days | Standard Deviation 6.95 |
| Galantamine and CBT | Cocaine Use | Baseline | 18.82 Days | Standard Deviation 8.68 |
| Galantamine | Cocaine Use | Baseline | 14.81 Days | Standard Deviation 9.05 |
| Galantamine | Cocaine Use | 12 Weeks | 6.32 Days | Standard Deviation 6.52 |
| Placebo and CBT | Cocaine Use | Baseline | 15.68 Days | Standard Deviation 7.78 |
| Placebo and CBT | Cocaine Use | 12 Weeks | 7.65 Days | Standard Deviation 7.41 |
| Placebo Only | Cocaine Use | 12 Weeks | 10.25 Days | Standard Deviation 7.79 |
| Placebo Only | Cocaine Use | Baseline | 14.85 Days | Standard Deviation 8.47 |
Secondary
Cognitive Function
A composite using a carefully selected neuropsychological battery that includes measures of executive cognitive functioning frequently affected among cocaine users, likely to be important moderators of CBT4CBT, and sensitive to galantamine effects. These will include measures of multiple aspects of attention, cognitive inhibition, sustained attention (CANTAB), decision making (BART), and memory (digit span). Scores ranged from -1.77 to 1.42 with a higher score indicating higher cognitive functioning.
Time frame: 12 weeks
Population: All participants did not complete the CANTAB assessments at both pre and post treatment. Reasons for not completing were refusal to complete the tasks, inability to complete the tasks in a manner in which they could be scored and equipment or computer problems.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine and CBT | Cognitive Function | -.12 scores on a scale | Standard Deviation 0.58 |
| Galantamine | Cognitive Function | .11 scores on a scale | Standard Deviation 0.5 |
| Placebo and CBT | Cognitive Function | -.06 scores on a scale | Standard Deviation 0.71 |
| Placebo Only | Cognitive Function | .03 scores on a scale | Standard Deviation 0.49 |