Cocaine Addiction
Conditions
Keywords
Drug Abuse, Cocaine, Addiction
Brief summary
The investigators' recently completed study has provided the first evidence that administration of the medication propranolol, following exposure to cocaine cues, can alter drug-associated memories and reduce craving and other drug cue-elicited responses in cocaine addicted persons. The investigators will attempt to augment this effect by a) doubling the number of propranolol-medicated cocaine cue exposure (CCE) retrieval sessions and b) increasing the dose of propranolol. It is expected that propranolol treated groups, relative to placebo treated groups, will evidence greater reduction of craving, cue reactivity and cocaine use during follow-up cocaine cue exposures. Also, these effects will be greater for those who receive 80mg of propranolol as opposed to 40mg.
Detailed description
Three groups of CD (cocaine dependant) participants will receive two sessions of cocaine cue exposure (CCE), each separated by a 24 hr. period and both conducted while the participants remain in hospital. One group (PBO) will receive placebo following each CCE session while the second (40PP) and third (80PP) group will receive 40 mg and 80 mg propranolol, respectively. Participants will return two days, and 1, 3, and 6 weeks after discharge and will be administered a CCE session to assess for maintenance/generalization of disruption of reconsolidation (DoR) effects on craving and cue reactivity to familiar and novel cocaine cues. Participants will also be assessed 3 times weekly for cocaine use (self-report & urine drug screen) during follow-up.
Interventions
DRUGPropranolol, 40 mg
DRUGPropranolol, 80 mg
DRUGPlacebo
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must meet DSM-IV criteria for current cocaine dependence (within the past month). Participants may meet criteria for abuse, but not dependence, for any other substance with the exception of nicotine. Because of the high comorbidity of cocaine and nicotine dependence, excluding nicotine dependence would seriously compromise the feasibility of recruitment (nicotine patch will be provided to participants during the course of their involvement in the laboratory procedures). Although individuals who meet criteria for alcohol abuse will be accepted for study participation, anyone who has a measurable blood alcohol level on the day of testing will be excluded as acute alcohol intake can lower seizure threshold. * Participants must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
Exclusion criteria
* Use of one of the following methods of birth control by female participants: barrier methods (diaphragm or condoms with spermicidal or both), surgical sterilization, use of an intra-uterine contraceptive device, or complete abstinence from sexual intercourse. * Individuals must live within a 50-mile radius of our research program and have reliable transportation. * Individuals must consent to remain abstinent from all drugs of abuse (except nicotine) for 72 hours immediately prior to CTRC inpatient admission. * Individuals must consent to random assignment to one of three study groups (the two propranolol-treated groups or the placebo-treated group).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Use | Evaluated at Weeks 1, 3 and 6 | Timeline of cocaine use throughout the duration of the study (in dollar amounts) |
| Change in Craving Score | Single-Item Craving Scores are collected at all Retrieval Extinction Sessions (medication days), as well as all Phase Two Test Sessions (weeks 1,3 and 6). | The participant is asked, What is the level of craving you are experiencing on a scale or 0 to 100, with 0 representing no craving and 100 extreme craving? |
| Days of Abstinence | Week 1, Week 3, and Week 6 | How many days the participants used cocaine versus how many days of abstinence they were able to achieve. |
| Average Peak Craving Score | Day 2, Week 1, Week 3, and Week 6 | Peak Craving Response from Session Baseline- peak craving is measured by a scale with a score of 0 (no craving) -100 (maximum craving). |
| Use Days | Week 1, Week 3, Week 6 | Mean Days of Cocaine Use |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Administered once orally following cue exposure on each of the first two days of testing.
Placebo | 59 |
| Propranolol 40mg Administered once orally following cue exposure on each of the first two days of testing.
Propranolol, 40 mg | 60 |
| Propranolol, 80mg Administered once orally following cue exposure on each of the first two days of testing.
Propranolol, 80 mg | 62 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 9 | 12 |
| Overall Study | Physician Decision | 9 | 6 | 6 |
Baseline characteristics
| Characteristic | Placebo | Propranolol 40mg | Propranolol, 80mg | Total |
|---|---|---|---|---|
| Age, Continuous | 44.8 years | 43.8 years | 42.3 years | 43.6 years |
| Race/Ethnicity, Customized African American | 34 Participants | 40 Participants | 42 Participants | 116 Participants |
| Race/Ethnicity, Customized Caucasian | 22 Participants | 19 Participants | 19 Participants | 60 Participants |
| Race/Ethnicity, Customized Mixed/Unknown | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Region of Enrollment United States | 59 participants | 60 participants | 62 participants | 181 participants |
| Sex: Female, Male Female | 20 Participants | 19 Participants | 25 Participants | 64 Participants |
| Sex: Female, Male Male | 39 Participants | 41 Participants | 37 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 60 | 0 / 62 |
| other Total, other adverse events | 0 / 59 | 1 / 60 | 0 / 62 |
| serious Total, serious adverse events | 0 / 59 | 0 / 60 | 0 / 62 |
Outcome results
Primary
Average Peak Craving Score
Peak Craving Response from Session Baseline- peak craving is measured by a scale with a score of 0 (no craving) -100 (maximum craving).
Time frame: Day 2, Week 1, Week 3, and Week 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Average Peak Craving Score | Week 1 | 15.2 score on a scale | Standard Error 3.5 |
| Placebo | Average Peak Craving Score | Day 2 | 16.1 score on a scale | Standard Error 3.5 |
| Placebo | Average Peak Craving Score | Week 3 | 13.1 score on a scale | Standard Error 3.6 |
| Placebo | Average Peak Craving Score | Week 6 | 10.2 score on a scale | Standard Error 3.6 |
| Propranolol 40mg | Average Peak Craving Score | Week 6 | 12.1 score on a scale | Standard Error 3.6 |
| Propranolol 40mg | Average Peak Craving Score | Week 3 | 19.7 score on a scale | Standard Error 3.6 |
| Propranolol 40mg | Average Peak Craving Score | Day 2 | 23.3 score on a scale | Standard Error 3.4 |
| Propranolol 40mg | Average Peak Craving Score | Week 1 | 19.6 score on a scale | Standard Error 3.5 |
| Propranolol, 80mg | Average Peak Craving Score | Day 2 | 18.1 score on a scale | Standard Error 3.3 |
| Propranolol, 80mg | Average Peak Craving Score | Week 1 | 17.1 score on a scale | Standard Error 3.5 |
| Propranolol, 80mg | Average Peak Craving Score | Week 3 | 10.1 score on a scale | Standard Error 3.5 |
| Propranolol, 80mg | Average Peak Craving Score | Week 6 | 5.5 score on a scale | Standard Error 3.7 |
Primary
Change in Craving Score
The participant is asked, What is the level of craving you are experiencing on a scale or 0 to 100, with 0 representing no craving and 100 extreme craving?
Time frame: Single-Item Craving Scores are collected at all Retrieval Extinction Sessions (medication days), as well as all Phase Two Test Sessions (weeks 1,3 and 6).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Craving Score | Day 2 | 25.6 score on a scale | Standard Error 3 |
| Placebo | Change in Craving Score | Week 1 | 27.5 score on a scale | Standard Error 2.8 |
| Placebo | Change in Craving Score | Week 3 | 24.6 score on a scale | Standard Error 2.9 |
| Placebo | Change in Craving Score | Week 6 | 22.6 score on a scale | Standard Error 2.8 |
| Propranolol 40mg | Change in Craving Score | Week 6 | 22.4 score on a scale | Standard Error 2.7 |
| Propranolol 40mg | Change in Craving Score | Day 2 | 31.4 score on a scale | Standard Error 2.9 |
| Propranolol 40mg | Change in Craving Score | Week 3 | 29.0 score on a scale | Standard Error 2.9 |
| Propranolol 40mg | Change in Craving Score | Week 1 | 28.0 score on a scale | Standard Error 2.8 |
| Propranolol, 80mg | Change in Craving Score | Week 6 | 17.5 score on a scale | Standard Error 2.8 |
| Propranolol, 80mg | Change in Craving Score | Week 1 | 24.7 score on a scale | Standard Error 2.7 |
| Propranolol, 80mg | Change in Craving Score | Week 3 | 20.0 score on a scale | Standard Error 2.9 |
| Propranolol, 80mg | Change in Craving Score | Day 2 | 26.9 score on a scale | Standard Error 2.9 |
Primary
Cocaine Use
Timeline of cocaine use throughout the duration of the study (in dollar amounts)
Time frame: Evaluated at Weeks 1, 3 and 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cocaine Use | Week 3 | 121.25 Dollar amounts of cocaine use | Standard Error 32.67 |
| Placebo | Cocaine Use | Week 1 | 58.9 Dollar amounts of cocaine use | Standard Error 31.95 |
| Placebo | Cocaine Use | Week 6 | 186.57 Dollar amounts of cocaine use | Standard Error 33.21 |
| Propranolol 40mg | Cocaine Use | Week 3 | 177.67 Dollar amounts of cocaine use | Standard Error 32.34 |
| Propranolol 40mg | Cocaine Use | Week 1 | 71.57 Dollar amounts of cocaine use | Standard Error 31.63 |
| Propranolol 40mg | Cocaine Use | Week 6 | 198.9 Dollar amounts of cocaine use | Standard Error 32.85 |
| Propranolol, 80mg | Cocaine Use | Week 1 | 69.63 Dollar amounts of cocaine use | Standard Error 30.74 |
| Propranolol, 80mg | Cocaine Use | Week 6 | 242.79 Dollar amounts of cocaine use | Standard Error 32.47 |
| Propranolol, 80mg | Cocaine Use | Week 3 | 135.81 Dollar amounts of cocaine use | Standard Error 31.93 |
Primary
Days of Abstinence
How many days the participants used cocaine versus how many days of abstinence they were able to achieve.
Time frame: Week 1, Week 3, and Week 6
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Days of Abstinence | Week 3 | 15 Days |
| Placebo | Days of Abstinence | Week 1 | 20 Days |
| Placebo | Days of Abstinence | Week 6 | 15 Days |
| Propranolol 40mg | Days of Abstinence | Week 3 | 14 Days |
| Propranolol 40mg | Days of Abstinence | Week 1 | 19 Days |
| Propranolol 40mg | Days of Abstinence | Week 6 | 9 Days |
| Propranolol, 80mg | Days of Abstinence | Week 1 | 17 Days |
| Propranolol, 80mg | Days of Abstinence | Week 6 | 7 Days |
| Propranolol, 80mg | Days of Abstinence | Week 3 | 13 Days |
Primary
Use Days
Mean Days of Cocaine Use
Time frame: Week 1, Week 3, Week 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Use Days | Week 3 | 3.33 Days | Standard Error 0.55 |
| Placebo | Use Days | Week 1 | 1.66 Days | Standard Error 0.54 |
| Placebo | Use Days | Week 6 | 4.9 Days | Standard Error 0.56 |
| Propranolol 40mg | Use Days | Week 3 | 3.15 Days | Standard Error 0.54 |
| Propranolol 40mg | Use Days | Week 1 | 1.61 Days | Standard Error 0.53 |
| Propranolol 40mg | Use Days | Week 6 | 4.49 Days | Standard Error 0.55 |
| Propranolol, 80mg | Use Days | Week 1 | 1.76 Days | Standard Error 0.52 |
| Propranolol, 80mg | Use Days | Week 6 | 6.06 Days | Standard Error 0.55 |
| Propranolol, 80mg | Use Days | Week 3 | 3.51 Days | Standard Error 0.54 |