Cocaine Abuse, Cocaine Addiction, Cocaine Dependence, Drug Abuse, Substance Abuse
Conditions
Keywords
cocaine, quetiapine fumarate, dependence, abuse, addiction, treatment
Brief summary
This placebo-controlled trial will test the effectiveness of Seroquel XR™ for the treatment of cocaine dependence in non-psychotic individuals who are cocaine dependent.
Detailed description
Cocaine abuse continues to be an epidemic. Co-morbid psychiatric disorders and high risks behaviors compound the morbidity, economic costs, and social destruction associated with this public health crisis. This is a 12 week, prospective, intent-to-treat, double-blind, randomized, placebo-controlled study of Seroquel XR™ versus matched placebo, combined with cognitive-behavioral group therapy, for the treatment of cocaine dependence in non-psychotic individuals. We will conduct this study at the American Lake (Tacoma) and Seattle campuses of the VA Puget Sound Health Care System, recruiting veteran and non-veteran participants currently using cocaine from the greater Pierce and King Counties region. It is anticipated that 120 subjects will be consented and screened for study participation and that 60 subjects will be randomized to treatment. After subjects have provided informed consent, they will enter a 1 week screening phase during which medical, psychiatric, and substance use measures and assessments will be administered to determine study eligibility. At baseline, we will assess cocaine use, cocaine craving, psychiatric symptoms, and high risk behaviors. Also at this visit, subjects will be randomly assigned to treatment with quetiapine (target dose 400 mg/day) or placebo. During the treatment phase, subjects will visit the clinic once a week for safety monitoring, completion of ratings and questionnaires, UDS's, and participation in a cognitive-behavioral therapy group. At end of study, week 12, a physical examination will be administered and a UDS and clinical laboratory values obtained. In addition, substance use, psychiatric symptoms, and high risk behaviors will be assessed. To monitor safety and further evaluate treatment effects, we will ask participants to return for a follow-up visit at week 16.
Interventions
DRUGquetiapine fumarate
At baseline, subjects in the experimental group will initially be administered 50 mg/day of Seroquel XR™ (extended release formulation of quetiapine fumarate), to be titrated up to 400 mg/day of Seroquel XR™ by the end of the second week. By the end of week 2, subjects will be stabilized on a dose of 400 mg/day or alternatively 300, 200, 100, or 50 mg/day of study drug, as tolerated. If a subject is unable to tolerate the 50 mg/day dose, he or she will be discontinued from the drug portion of the study.
DRUGMatched Placebo
Subjects randomized to the placebo comparator group will follow the same titration and dosing procedures as the experimental group, but will receive matched placebo tablets.
BEHAVIORALCognitive-behavioral Therapy
During the 12 week treatment phase, all subjects attended weekly group cognitive-behavioral therapy sessions. This therapy platform utilized the cognitive-behavioral therapy manual, Seeking Safety. Seeking Safety has been shown to effectively reduce substance use and to improve psychological functioning in a variety of populations.
Sponsors
VA Puget Sound Health Care System
AstraZeneca
Seattle Institute for Biomedical and Clinical Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of written informed consent 2. Males and females aged 18-65 years 3. Female subjects of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at the screening and baseline visits and agree to use one of the following methods of birth control: a) oral contraceptive, b) patch, c) intrauterine progesterone or non-hormonal contraceptive system, d) levonorgestrel implant, e) medroxyprogesterone acetate contraceptive injection, or f) complete abstinence from sexual intercourse 4. A diagnosis of current cocaine dependence; as determined by the Structured Clinical Interview for DSM-IV-TR Axis I Disorders 69 (SCID-I/P) 5. Has used cocaine within the 30 days prior to screening 6. Able to understand and comply with the requirements of the study 7. Is seeking treatment for cocaine dependence 8. Is able to provide a reliable primary contact phone number and is able to provide a reliable alternate contact address and phone number, such as for a relative or close friend 9. Anticipates no life changes that would preclude study completion
Exclusion criteria
1. Pregnancy or lactation 2. Currently hospitalized or in a detoxification program 3. Physiological dependence on alcohol, sedative/hypnotic, or any other substance requiring medical detoxification 4. Current diagnosis of psychotic disorder, including bipolar disorder with psychotic features, as determined by the SCID-I/P or clinical interview 5. Subjects who are judged by the investigator to be psychiatrically unstable, including posing an imminent risk of suicide or a danger to self or others, as determined by the SCID-I/P, CGI-S, Hamilton Anxiety Rating Scale(HAM-A), Hamilton Rating Scale for Depression(HAM-D), or clinical interview 6. Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator 7. Has a history of neuroleptic malignant syndrome or other serious adverse reaction to antipsychotic medication 8. Use of any antipsychotic medication within the 30 days preceding baseline 9. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days prior to baseline including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluoxetine, fluvoxamine, paroxetine, and saquinavir 10. Use of any of the following cytochrome P450 inducers in the 14 days prior to baseline including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids 11. Evidence of any clinically relevant disease (e.g., renal, hepatic, gastrointestinal, pulmonary, cardiac, or cerebrovascular disease, AIDS, cancer, asthma, neurological or neuromuscular disease, seizure disorder, or clinically significant abnormal laboratory value) or any clinical finding that in the judgment of the investigator could potentially be negatively affected by study participation or that could potentially affect study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Timeline Followback Interview (TLFB) | Grams of cocaine used at end of study (12-weeks) | The primary outcome measure was the self-report of cocaine use in the past week, as assessed with a Timeline Followback Interview (TLFB). The TLFB is a questionnaire in which the subject is asked to self-report how much cocaine was used and how much money was spent on cocaine every day for the past 1-2 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Attaining Abstinence for Three Weeks | Abstinence defined as negative UDS for 3 consecutive weeks of the trial | Abstinence was defined as a negative urine drug screen (UDS) (for cocaine) for three consecutive weeks of the trial measure at either time point Week 6 or Week 12 |
Countries
United States
Participant flow
Recruitment details
Participants with a diagnosis of cocaine dependence were recruited from the VA Puget Sound Health Care System and the local community.
Pre-assignment details
A screening visit was conducted to ensure that they met inclusion/exclusion criteria for the study. If they met criteria, they were scheduled for a baseline visit, during which they were randomized to either the quetiapine or placebo arm of the study.
Participants by arm
| Arm | Count |
|---|---|
| Study Drug Oral quetiapine | 29 |
| Placebo Placebo (sugar pill) | 31 |
| Total | 60 |
Baseline characteristics
| Characteristic | Placebo | Study Drug | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 29 Participants | 60 Participants |
| Age, Continuous | 47.71 years STANDARD_DEVIATION 9.69 | 48.11 years STANDARD_DEVIATION 6.97 | 47.90 years STANDARD_DEVIATION 8.38 |
| Region of Enrollment United States | 31 participants | 29 participants | 60 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 26 Participants | 26 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 29 | 24 / 31 |
| serious Total, serious adverse events | 1 / 29 | 1 / 31 |
Outcome results
Primary
Timeline Followback Interview (TLFB)
The primary outcome measure was the self-report of cocaine use in the past week, as assessed with a Timeline Followback Interview (TLFB). The TLFB is a questionnaire in which the subject is asked to self-report how much cocaine was used and how much money was spent on cocaine every day for the past 1-2 weeks.
Time frame: Grams of cocaine used at end of study (12-weeks)
Population: At end of study(12-weeks) 11 participants remained in the quetiapine group and 9 participants remained in the placebo group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug | Timeline Followback Interview (TLFB) | 0.11 grams of cocaine used | Standard Deviation 0.3 |
| Placebo | Timeline Followback Interview (TLFB) | 0.63 grams of cocaine used | Standard Deviation 1.78 |
Comparison: We used a repeated-measures ANCOVA to compare cocaine usage between the two groups. This incorporated the multiple administrations of the Timeline Followback measure.p-value: <0.25ANCOVA
Secondary
Percentage of Participants Attaining Abstinence for Three Weeks
Abstinence was defined as a negative urine drug screen (UDS) (for cocaine) for three consecutive weeks of the trial measure at either time point Week 6 or Week 12
Time frame: Abstinence defined as negative UDS for 3 consecutive weeks of the trial
Population: At end of study (12-weeks) 11 participants remained in the quetiapine group and 9 participants remained in the placebo group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Drug | Percentage of Participants Attaining Abstinence for Three Weeks | 45.5 Percentage of Participants |
| Placebo | Percentage of Participants Attaining Abstinence for Three Weeks | 44.4 Percentage of Participants |
Comparison: End-of-trial abstinence was defined as a negative urine drug screen (for cocaine) for three consecutive weeks at the end of the study.p-value: 0.65Regression, Cox