Investigation of Mifepristone (RU486) on Stress Sensitivity and Relapse Prevention in Cocaine Dependent Patients

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01134198
• Collaborator: (none)
• Enrollment: 58
• Location: 1
• Arms: 2
• Duration (Months): 93.5
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence	Drug: Mifepristone; Drug: placebo	Phase 2/Phase 3

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Investigation of the Effects of Mifepristone (RU486) on Stress Sensitivity and Relapse Prevention in Cocaine Dependent Patients
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Feb 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Mifepristone Mifepristone 600mg	Drug: Mifepristone; Mifepristone 600mg, 3x/wk for 4 weeks; Other Names: RU486
Placebo Comparator: placebo Placebo	Drug: placebo; placebo

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: Male
• Accepts 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 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.

1. Female

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	STARS	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

• Principal Investigator: Wilfid N Raby, Md, PhD, NYSPI

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wilfrid Raby, Principal Investigator, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01134198
• Other Study ID Numbers: 6013; RU486 for Cocaine Dependence
• First Posted: May 31, 2010
• Last Update Posted: Dec 20, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Wilfrid Raby, Principal Investigator, New York State Psychiatric Institute: Cocaine Dependence
• Additional relevant MeSH terms: Cocaine-Related Disorders; Mifepristone

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Mifepristone	Placebo
Arm/Group Description	Mifepristone 600mg Mifepristone: Mifepristone 600mg, 3x/wk for 4 weeks	Placebo placebo: placebo
Period Title: Phase 1
STARTED	16	13
COMPLETED	9	11
NOT COMPLETED	7	2
Period Title: Phase 1
STARTED	9	11
COMPLETED	9	7
NOT COMPLETED	0	4

Baseline Characteristics

Arm/Group Title	Mifepristone	Placebo	Total
Arm/Group Description	demographics for 16 participants who were randomized and started Phase 1. Mifepristone 600mg, 3x/wk for 4 weeks.	demographics for 13 participants who were randomized and started Phase 1. Placebo 600mg, 3x/week for 4 weeks	Total of all reporting groups
Overall Participants	16	13	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46 (8.3)	46 (8.3)	46 (8.3)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	16 100%	13 100%	29 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 31.3%	5 38.5%	10 34.5%
Not Hispanic or Latino	11 68.8%	8 61.5%	19 65.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 43.8%	5 38.5%	12 41.4%
White	3 18.8%	2 15.4%	5 17.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 37.5%	6 46.2%	12 41.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Relapse by Days 10 and 28
Description	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

Outcome Measure Data

Analysis Population Description

participants entering phase 2 of trial

Arm/Group Title	Mifepristone	Placebo
Arm/Group Description	Mifepristone 600mg Mifepristone: Mifepristone 600mg, 3x/wk for 4 weeks	Placebo placebo: placebo
Measure Participants	9	11
relapsed	3 18.8%	8 61.5%
abstinent	6 37.5%	3 23.1%
relapsed	5 31.3%	8 61.5%
abstinent	4 25%	3 23.1%

Adverse Events

Time Frame	Over 9 weeks (1 week of inpatient in phase 1 and 8 weeks in outpatient phase 2)
Arm/Group Title	Mifepristone		Placebo
Arm/Group Description	Mifepristone 600mg Mifepristone: Mifepristone 600mg, 3x/wk for 4 weeks		Placebo placebo: placebo
All Cause Mortality
	Mifepristone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Mifepristone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Mifepristone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/16 (81.3%)		5/13 (38.5%)
Blood and lymphatic system disorders
elevated eosinophils	1/16 (6.3%)	1	0/13 (0%)	0
Gastrointestinal disorders
nausea	5/16 (31.3%)	5	3/13 (23.1%)	3
constipation	2/16 (12.5%)	2	1/13 (7.7%)	1
General disorders
fatigue	2/16 (12.5%)	2	1/13 (7.7%)	1
weakness	2/16 (12.5%)	2	1/13 (7.7%)	1
insomnia/hypersomnia	2/16 (12.5%)	2	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.