Clinical trial NCT01134198: Investigation of Mifepristone (RU486) on Stress Sensitivity and Relapse Prevention in Cocaine Dependent Patients
Official title: Investigation of the Effects of Mifepristone (RU486) on Stress Sensitivity and Relapse Prevention in Cocaine Dependent Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Cocaine Dependence
Keywords: Cocaine Dependence
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
First posted: 2010-05-31
Enrollment: 58
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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 exclusion criteria for cold pressor test (CPT): history of frostbite, open cut or sore on foot to be immersed, history of Raynaud's phenomenon. During the testing, if sBP \> 190 or dBP \> 120, or HR \> 160, the test will be interrupted. A second occurrence of these values will stop all further CPT.

13: Patients taking medications metabolized by cytochrome 3A4 (ex: erythromycin, protease inhibitors) or that inhibit this cytochrome; or consuming grapefruit juice.

14: Patients with an underlying hemorrhagic disorder and those on anti-coagulants. INR \> 1.1, PT \> 17 msecs, total plt \<100x109/L.

15: Use of treatment agents that inhibit steroid biosynthesis by the adrenal cortex, such as metyrapone, ketoconazole, fluconazole, aminoglutethimide, or etomidate. Patients also requiring inhaled steroids.

16. Female

Primary outcomes:
measure: Number of Participants With Relapse by Days 10 and 28
timeFrame: assessed during 8 weeks of trial, but reported for days 10 and 28 of trial
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: STARS
state: New York
Study officials:
affiliation: NYSPI
name: Wilfid N Raby, Md, PhD
role: PRINCIPAL_INVESTIGATOR
References: