Alcoholism
Conditions
Keywords
Alcohol, Relapse
Brief summary
The primary hypotheses under test are that alcohol dependent subjects treated with mifepristone will report decreased craving for alcohol following alcohol exposure in the laboratory and report significantly less drinking under naturalistic conditions, than those treated with placebo.
Interventions
DRUGKorlym (mifepristone)
600 mg/day, oral pill, 7 days
DRUGSugar Pill
600 mg/day, oral pill, 7 days
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
The Scripps Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female volunteers, 18-65 years of age * Meets Diagnostic and Statistical Manual of Mental Disorders Fourth Addition (DSM-IV) criteria for current alcohol dependence * Subjects will not be seeking treatment because the medication studies are not treatment trials * Subjects must be abstinent a minimum of 3 days (but not more than 7 days) prior to the human lab session * Negative Breath Alcohol Concentration (BAC) and a Clinical Institute Withdrawal Assessment-Alcohol (CIWA-A) score of \< 8 at screening and time of lab session to eliminate acute alcohol or withdrawal effects on dependent measures * Subjects must be able to complete and understand questionnaires and study procedures in English and sign an informed consent
Exclusion criteria
* Significant medical disorders that will increase potential risk or interfere with study participation as determined by the Study Physician * Female subjects with childbearing potential who are pregnant, nursing, or refuse to use double barrier (non-hormonal) methods of birth control for the duration of the study and one month thereafter * Meets DSM-IV criteria for a major Axis I disorder including mood or anxiety disorders or substance dependence disorders other than alcohol or nicotine dependence * History of allergy or hypersensitivity to the study drugs or the ingredients * Treatment within the month prior to screening with 1.) an investigational drug or vaccine; 2.) drugs that may influence study outcomes, e.g., disulfiram (Antabuse), naltrexone (ReVia), acamprosate (Campral), anticonvulsants, antidepressants. * In need of or currently taking any psychoactive medications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Craving to Drink | 1 week | Visual Analog Scale (VAS) scores of craving severity in response to in vivo alcohol cues. Higher scores indicate greater craving severity with a minimum score of 0 and a maximum score of 80. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Drinking | 2 weeks | Number of standard drinks per week using the Timeline Followback Interview. Total number of alcoholic drinks consumed per week with a minimum value of 0 and a maximum value of 70. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited for study participation at the Laboratory of Clinical Psychopharmacology at The Scripps Research Institute in La Jolla, CA from 03/16/2012-03/14/2014. One Hundred twenty nine non-treatment seeking, paid volunteers signed informed consent, Fifty six subjects were enrolled, and Fifty four subjects completed the study.
Pre-assignment details
Sixty six subjects were excluded from study participation due to exclusionary criteria, 2 subjects did not return after Visit 1, 4 subjects withdrew consent (2 for time constraints following Visit 1, 1 due to social motivations, 1 due to moving out of state), and 1 subject left the lab during Visit 1 when asked to provide a urine sample.
Participants by arm
| Arm | Count |
|---|---|
| Korlym (Mifepristone) Korlym (mifepristone): 600 mg/day, oral pill, 7 days | 28 |
| Placebo Sugar Pill: placebo, oral pill, 7 days | 28 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Korlym (Mifepristone) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 41.2 years STANDARD_DEVIATION 11.4 | 36.9 years STANDARD_DEVIATION 11.2 | 39.1 years STANDARD_DEVIATION 11.4 |
| DSM-IV symptom count | 4.7 number of symptoms STANDARD_DEVIATION 1.5 | 5.1 number of symptoms STANDARD_DEVIATION 1.5 | 4.8 number of symptoms STANDARD_DEVIATION 1.5 |
| DSM-V symptom count | 6.2 number of symptoms STANDARD_DEVIATION 2.3 | 6.9 number of symptoms STANDARD_DEVIATION 2.1 | 6.5 number of symptoms STANDARD_DEVIATION 2.2 |
| 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 | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 21 Participants | 44 Participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Male | 23 Participants | 20 Participants | 43 Participants |
| Years of heavy drinking | 15.0 years STANDARD_DEVIATION 11 | 14.0 years STANDARD_DEVIATION 8.9 | 14.5 years STANDARD_DEVIATION 9.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 28 | 8 / 26 |
| serious Total, serious adverse events | 0 / 28 | 0 / 26 |
Outcome results
Primary
Craving to Drink
Visual Analog Scale (VAS) scores of craving severity in response to in vivo alcohol cues. Higher scores indicate greater craving severity with a minimum score of 0 and a maximum score of 80.
Time frame: 1 week
Population: 1 participant who completed the study had missing VAS scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Korlym (Mifepristone) | Craving to Drink | 36.5 units on a scale | Standard Error 1.5 |
| Sugar Pill | Craving to Drink | 42.9 units on a scale | Standard Error 1.5 |
Comparison: Linear Mixed Effects Modeling (MEM) with Restricted Maximum Likelihood estimation was used to measure differences in alcohol-cued craving..p-value: 0.003Mixed Models Analysis
Secondary
Drinking
Number of standard drinks per week using the Timeline Followback Interview. Total number of alcoholic drinks consumed per week with a minimum value of 0 and a maximum value of 70.
Time frame: 2 weeks
Population: Three randomized subjects who met exclusionary criteria were not included in the regression analysis for drinking: two subjects were excluded for unreliable reporting and one subject was excluded for being treatment seeking.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Korlym (Mifepristone) | Drinking | 27.661 alcoholic drinks per week | Standard Error 3.176 |
| Sugar Pill | Drinking | 38.175 alcoholic drinks per week | Standard Error 3.239 |
Comparison: Linear Mixed Effect Modeling (MEM) with Restricted Maximum Likelihood estimation was used to measure differences in changes in drinking.p-value: 0.05Mixed Models Analysis
Comparison: Data represent the estimated marginal mean + or - SEM. \*P\<0.05, mifepristone vs. placebo (linear mixed effects modeling).p-value: <0.05Mixed Models Analysis