Cocaine Dependence
Conditions
Keywords
Cocaine Dependence
Brief summary
This research will evaluate the impact of blocking central and peripheral glucocorticoid receptors on stress sensitivity and the risk of relapse to cocaine use in treatment-seeking cocaine-dependent individuals. Mifepristone (RU-486) will be the glucocorticoid antagonist used.
Detailed description
This study attempts to reduce relapse risk by blocking glucocorticoid receptors, and thus allow some of the changes in the brain caused by cocaine to redress themselves
Interventions
DRUGMifepristone
Mifepristone 600mg, 3x/wk for 4 weeks
DRUGplacebo
placebo
Sponsors
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 60. 2. Male. 3. Meets DSM?IV criteria for current cocaine dependence and is seeking treatment. 4. Identifies life stress (work, interpersonal, financial, etc) as a trigger for cocaine use or reports uncontrollable craving to use of cocaine. 5. Displays at least one cocaine-positive urine toxicology during screening. 6. Uses cocaine at least 4/30 days in the past month, or reports episodic binges of large amounts of cocaine (at least $200) at least 2x/month. 7. Able to give informed consent and comply with study procedures.
Exclusion criteria
1. Meets DSM-IV criteria for major depression, bipolar disorder, schizophrenia or any psychotic disorder other than transient psychosis due to drug abuse. Substance Induced Mood Disorder with Hamilton Depression Scale score ³13 will be excluded. 2. History of seizures in the last 2 years, or history of seizures related to the substance (cocaine, alcohol, or benzodiazepine) that the patient continues to use. 3. History of allergic, dermatological, or adverse event to mifepristone 4. Chronic organic mental disorder, insufficient proficiency in English that would render an individual incapable of giving informed consent. 5. Significant current suicidal risks, history of significant suicidal behavior or any suicide attempt within the past year. 6. Unstable physical disorders, which might make participation hazardous such as hypertension (\>140/90), WBC \< 3.5, new diagnosis of hepatitis (patients with chronic mildly elevated transaminase levels (£2-3 X upper limit of normal will be considered acceptable if PT/PTT is normal), renal failure (creat \> 2; BUN \> 40), or diabetes (HbA1c \> 7%), and low Hb (\< 12g/dL) or low Hct (\<36%). 7. Coronary vascular disease as indicated by history, or suspected by abnormal ECG or history of cardiac symptoms. Hx of cardiac symptoms (chest pain, chest pressure, shortness of breath, syncope) during cocaine use. 8. Cardiac conduction system disease as indicated by QRS duration of ³ 0.11 msec. 9. Currently meets DSM-IV criteria for another substance dependence or abuse disorder other than nicotine, alcohol, or cannabis. If alcohol dependent, must not be in need of detoxification. Heavy male drinkers (who consume greater than 5 standard alcoholic drink per day per NIAAA definition) will be excluded. 10. Presents with metabolic indicators of hypoadrenalism such as low serum sodium (\<130 mEq/L), high serum potassium (\>5.5 mEq/L), Na/K ratio \< 30:1, low fasting blood sugar (\<50 mg/dL), or high BUN (\>20 mg/dL), or a previous history of Addison's disease or adrenal insufficiency, or the presence of low K (\< 3.5 mEq/L). spot AM cortisol \<5ug/dL, PM cortisol \< 3 ug/dL 11. Participants who cannot comply with study procedures during the initial hospitalization phase. 12. Supplemental
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Relapse by Days 10 and 28 | assessed during 8 weeks of trial, but reported for days 10 and 28 of trial | assessed percent of sample with documented cocaine use by days 10 and 28 based on self reported use and urine toxicology. Those with documented use were considered to have relapsed. |
Countries
United States
Participant flow
Pre-assignment details
58 participants signed consent and were enrolled into the trial. Only 32 entered the randomized phase of the study with only 29 being assigned to one of the treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Mifepristone demographics for 16 participants who were randomized and started Phase 1.
Mifepristone 600mg, 3x/wk for 4 weeks. | 16 |
| Placebo demographics for 13 participants who were randomized and started Phase 1.
Placebo 600mg, 3x/week for 4 weeks | 13 |
| Total | 29 |
Baseline characteristics
| Characteristic | Placebo | Total | Mifepristone |
|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 8.3 | 46 years STANDARD_DEVIATION 8.3 | 46 years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 19 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 12 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 13 Participants | 29 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 16 | 5 / 13 |
| serious Total, serious adverse events | 0 / 16 | 0 / 13 |
Outcome results
Primary
Number of Participants With Relapse by Days 10 and 28
assessed percent of sample with documented cocaine use by days 10 and 28 based on self reported use and urine toxicology. Those with documented use were considered to have relapsed.
Time frame: assessed during 8 weeks of trial, but reported for days 10 and 28 of trial
Population: participants entering phase 2 of trial
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Mifepristone | Number of Participants With Relapse by Days 10 and 28 | Day 10 | abstinent | 6 Participants |
| Mifepristone | Number of Participants With Relapse by Days 10 and 28 | Day 28 | relapsed | 5 Participants |
| Mifepristone | Number of Participants With Relapse by Days 10 and 28 | Day 10 | relapsed | 3 Participants |
| Mifepristone | Number of Participants With Relapse by Days 10 and 28 | Day 28 | abstinent | 4 Participants |
| Placebo | Number of Participants With Relapse by Days 10 and 28 | Day 28 | abstinent | 3 Participants |
| Placebo | Number of Participants With Relapse by Days 10 and 28 | Day 10 | abstinent | 3 Participants |
| Placebo | Number of Participants With Relapse by Days 10 and 28 | Day 10 | relapsed | 8 Participants |
| Placebo | Number of Participants With Relapse by Days 10 and 28 | Day 28 | relapsed | 8 Participants |