Cocaine Related Disorders
Conditions
Keywords
Cocaine Addiction, Cocaine Dependence
Brief summary
Stressful situations and cues associated with cocaine can lead to craving in cocaine dependent individuals. The purpose of this study is to determine whether guanfacine or modafinil are effective in reducing stress and cue induced craving in cocaine dependent individuals.
Detailed description
Stress and cocaine cues produce craving and ultimately relapse in cocaine dependent individuals. This is a randomized, double-blind, placebo-controlled study evaluating the effects of either guanfacine (Tenex) or modafinil (Provigil) on stress and cue induced craving in cocaine dependent individuals. Cocaine dependence will be assessed in adults (ages 18-65) as defined by DSM-IV criteria. If the subject signs the consent form, meets the study criteria and does not meet the exclusion criteria they will be included in the study. Subjects will report to the General Clinical Research Center (GCRC) at the Medical University of South Carolina (MUSC), for an outpatient visit and will receive their first dose of study medication. The following day subjects will return to the GCRC and admitted for the duration of the study (two days and one night). There will be a one-week and a one-month follow-up visit. Subjects will be randomly assigned to one of two treatment groups (guanfacine or placebo). Each subject will also be randomly assigned to either a stress or no-stress subgroup. On the test day (day 3) subjects in the stress group will be asked to perform a speech and a math problem in front of an audience (Trier Social Stress Test, TSST), while the no-stress group will be asked to sit quietly and read. Following these tasks, each subject will be exposed to neutral (control) cues and immediately afterwards the subjects will be exposed to cocaine cues (cocaine paraphernalia). Craving/mood, physiological activity, and endocrine responses, will be assessed at pre-set intervals throughout the testing procedure. The cue reactivity protocol will be repeated on the one-week follow-up visit.
Interventions
DRUGGuanfacine
DRUGModafinil
DRUGPlacebo
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) during the GCRC admission. Because of the high comorbidity of alcohol and marijuana use and cocaine dependence, individuals meeting dependence for alcohol and marijuana will be included. Individuals requiring medical detox from alcohol will be excluded. Subjects must consent to random assignment to stress vs. no stress and drug treatment conditions.
Exclusion criteria
Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control. Modafinil inhibits metabolism of steroidal contraceptives via CYP3A4 and can reduce the effectiveness of this type of birth control, female subjects must use one of the following methods of birth control: barrier methods (diaphragm or condoms with spermicide or both), surgical sterilization, use of an intra-uterine contraceptive device, or complete abstinence from sexual intercourse. Subjects with evidence of or a history of significant hematological, endocrine, cardiovascular (including but not limited to left ventricular hypertrophy (unless a cardiologist deems that it is not clinically significant), mitral valve prolapse, left bundle branch block, myocardial infarction, and angina), pulmonary, renal, gastrointestinal, or neurological disease including diabetes, as these conditions may affect HPA axis function. Subjects with any liver function test (LFTs) of greater than two times normal, as compromised liver function can interfere with HPA axis activity (Williams and Dluhy 1987) and may affect drug metabolism. Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal cortex likely to affect HPA axis function. Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may interfere with HPA function. Subjects with current major depressive disorder or post-traumatic stress disorder as these disorders are associated with characteristic changes in HPA axis function. Subjects receiving synthetic glucocorticoid therapy, any exogenous steroid therapy, or treatment with other agents that interfere with HPA axis function within one month of the time of testing. Subjects taking any psychotropic medications, opiates or opiate antagonists because these may affect HPA axis function.Participants taking SSRI's will be included. Subjects required to take medications that could adversely interact with study medications, including, but not limited to, azole type antifungals, cyclosporine, warfarin, theophylline, or carbamazepine. Any medications that induce or inhibit CYP3A4 pathways are excluded, as modafinil is metabolized through this enzyme system. Subjects with any acute illness or fever as this may affect HPA axis activity. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation. Subjects who are grossly obese (BMI \> 39), as this may interfere with HPA axis function. Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of abuse (except nicotine) prior to the stress task procedure. Subjects meeting DSM-IV criteria for substance dependence (other than nicotine, cocaine, alcohol or marijuana) within the past 60 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Craving | Post Trier social stress task + Cocaine Cue 2:30 pm | Participants were randomized to the modafinil, guanfacine, or placebo treatment group. Participants were then randomized to participate in the TRIER social stress task or to read magazines for 15 minutes. Following the task, participants were exposed to neutral cues for 2 minutes and cocaine cues for 2 minutes. Immediately following the cocaine cue exposure, participants were asked to rate cocaine craving on a 10-point Likert scale, with 0 being Not at All and 10 being Extremely. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cortisol- 2:30 pm, Immediately Following Trier Social Stress Task + Cocaine Cue Exposure | Immediately following trier + cocaine cue exposure | Participants were randomized to receive to the modafinil, guanfacine, or placebo treatment group. Participants were then randomized to complete a TRIER social stress task or read magazines for 15 minutes. Following the task, participants were exposed to neutral cues for two minutes and control cues for two minutes. Immediately following exposure to the cocaine cue, saliva samples were collected to measure cortisol levels. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited between April 2008 and May 2012. Participants were primarily recruited through newspaper and television advertisements and respondent driven sampling. All study procedures took place at the Medical University of South Carolina.
Pre-assignment details
50 participants were enrolled and dropped for unknown reason. 22 participants were enrolled but failed the urine drug screen. 2 participants were unable to complete due to obtaining employment. 2 participants completed procedures, but were later discovered to have bipolar disorder. Their data was not used.
Participants by arm
| Arm | Count |
|---|---|
| Modafinil/Stress Participants received Modafinil for three days and completed a TRIER social stress task on the third day. | 13 |
| Modafinil/No Stress Participants received modafinil for 3 days and did not complete the TRIER social stress task on the third day. | 12 |
| Guanfacine/Stress Participants received placebo for 2 days, guanfacine for 1 day, and completed the TRIER social stress task on the third day. | 26 |
| Guanfacine/No Stress Participants received placebo for 2 days, guanfacine for 1 day, and did not complete the TRIER social stress task on the third day. | 24 |
| Placebo/Stress Participants received placebo for 3 days and completed the TRIER social stress task on the third day. | 15 |
| Placebo/No Stress Participants received placebo for 3 days and did not complete the TRIER social stress task on the third day. | 19 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 3 | 3 | 2 | 3 |
Baseline characteristics
| Characteristic | Modafinil/No Stress | Guanfacine/Stress | Guanfacine/No Stress | Modafinil/Stress | Placebo/Stress | Placebo/No Stress | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 26 Participants | 24 Participants | 13 Participants | 15 Participants | 19 Participants | 109 Participants |
| Age, Continuous | 38.5 years STANDARD_DEVIATION 10.49 | 41 years STANDARD_DEVIATION 10.05 | 40.92 years STANDARD_DEVIATION 9.55 | 42.46 years STANDARD_DEVIATION 8.03 | 40.2 years STANDARD_DEVIATION 9.13 | 44 years STANDARD_DEVIATION 8.6 | 41.41 years STANDARD_DEVIATION 9.28 |
| Region of Enrollment United States | 12 participants | 26 participants | 24 participants | 13 participants | 15 participants | 19 participants | 109 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants | 3 Participants | 3 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Male | 9 Participants | 25 Participants | 20 Participants | 10 Participants | 12 Participants | 14 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 0 / 12 | 0 / 26 | 0 / 24 | 0 / 15 | 0 / 19 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 | 0 / 26 | 0 / 24 | 0 / 15 | 0 / 10 |
Outcome results
Primary
Cocaine Craving
Participants were randomized to the modafinil, guanfacine, or placebo treatment group. Participants were then randomized to participate in the TRIER social stress task or to read magazines for 15 minutes. Following the task, participants were exposed to neutral cues for 2 minutes and cocaine cues for 2 minutes. Immediately following the cocaine cue exposure, participants were asked to rate cocaine craving on a 10-point Likert scale, with 0 being Not at All and 10 being Extremely.
Time frame: Post Trier social stress task + Cocaine Cue 2:30 pm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil/Stress | Cocaine Craving | 3.08 units on a scale | Standard Deviation 3.59 |
| Modafinil/No Stress | Cocaine Craving | 4.36 units on a scale | Standard Deviation 2.84 |
| Guanfacine/Stress | Cocaine Craving | 1.54 units on a scale | Standard Deviation 3.06 |
| Guanfacine/No Stress | Cocaine Craving | 3.13 units on a scale | Standard Deviation 3.49 |
| Placebo/Stress | Cocaine Craving | 1.8 units on a scale | Standard Deviation 2.8 |
| Placebo/No Stress | Cocaine Craving | 2.11 units on a scale | Standard Deviation 2.4 |
Secondary
Cortisol- 2:30 pm, Immediately Following Trier Social Stress Task + Cocaine Cue Exposure
Participants were randomized to receive to the modafinil, guanfacine, or placebo treatment group. Participants were then randomized to complete a TRIER social stress task or read magazines for 15 minutes. Following the task, participants were exposed to neutral cues for two minutes and control cues for two minutes. Immediately following exposure to the cocaine cue, saliva samples were collected to measure cortisol levels.
Time frame: Immediately following trier + cocaine cue exposure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil/Stress | Cortisol- 2:30 pm, Immediately Following Trier Social Stress Task + Cocaine Cue Exposure | 12.55 mcg/dl | Standard Deviation 3.27 |
| Modafinil/No Stress | Cortisol- 2:30 pm, Immediately Following Trier Social Stress Task + Cocaine Cue Exposure | 11.69 mcg/dl | Standard Deviation 5.57 |
| Guanfacine/Stress | Cortisol- 2:30 pm, Immediately Following Trier Social Stress Task + Cocaine Cue Exposure | 13.19 mcg/dl | Standard Deviation 5.36 |
| Guanfacine/No Stress | Cortisol- 2:30 pm, Immediately Following Trier Social Stress Task + Cocaine Cue Exposure | 9.06 mcg/dl | Standard Deviation 2.19 |
| Placebo/Stress | Cortisol- 2:30 pm, Immediately Following Trier Social Stress Task + Cocaine Cue Exposure | 12.42 mcg/dl | Standard Deviation 3.95 |
| Placebo/No Stress | Cortisol- 2:30 pm, Immediately Following Trier Social Stress Task + Cocaine Cue Exposure | 8.94 mcg/dl | Standard Deviation 2.48 |