Alcohol Abuse, Alcohol Dependence, Alcoholism, Alcohol Use Disorders
Conditions
Keywords
Alcohol-Related Disorders, Substance-Related Disorders, Mental Disorders, Mifepristone, Glucocorticoid Antagonists, Alcohol Treatment, Alcohol
Brief summary
This is an 8-week, randomized, double-blind, placebo-controlled, 2 arm, parallel groups, study of 1-week of treatment with mifepristone (0, 1200 mg/d) given in conjunction with 8 weeks of manual-guided counseling, and a follow-up visit at Week 12.
Interventions
Mifepristone, 300 mg tablets, Four tablets daily/am for 1-week duration.
BEHAVIORALStandardized behavioral therapy
Standardized behavioral therapy 1 time per week for 8 week duration.
DRUGPlacebo
Placebo tablets, Four tablets daily/am for 1-week duration.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
The Scripps Research Institute
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
* Male or female volunteers, 18-65 years of age * Meets Diagnostic and Statistical Manual (DSM)-V criteria for current alcohol use disorder of moderate or greater severity, defined by DSM-V as ≥ 4 symptoms * Abstinent a minimum of 3 days (but not more than 30 days) prior to randomization * In acceptable health in the judgment of the study physician, on the basis of interview, medical history, physical exam, ECG, urine test and lab tests * Females with childbearing potential must have a negative serum pregnancy test on the screening visit and a negative urine pregnancy test at randomization and agree to use non-hormonal effective birth control for the study duration and one month thereafter
Exclusion criteria
* A medical condition or chronic use of a medication that contraindicates the administration of mifepristone * Significant medical disorders or clinically significant findings on ECG (e.g., prolongation of the corrected QT interval,urine or blood tests that increase potential risk or interfere with study participation as determined by the Study Physician. Note: serum potassium below the normal range must be replaced to normal prior to randomization; individuals with serum potassium outside the range of normal will not be randomized * Liver function tests more than 3 times the upper limit of normal or elevated bilirubin * Female subjects with childbearing potential who are pregnant, nursing, or refuse to use effective non hormonal birth control for the 1-week of medication administration and one month thereafter * Meets Diagnostic and Statistical Manual -V criteria for a major Axis I disorder including mood or anxiety disorders or substance use disorders other than alcohol or nicotine use disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drinking Quantity Per Day | Participants will be followed for up to 12 weeks post-assignment | Drinking quantity in standard drinks per day is measured by the Timeline Followback interview. A standard drink contains 14 grams of alcohol, e.g., 1.5 ounces of distilled spirits, 5 ounces of wine, or 12 ounces of beer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Craving | Participants will be followed for up to 12 weeks | Alcohol Craving Questionnaire; minimum value equals 12, maximum value equals 84; higher scores mean greater craving for alcohol. |
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 10/13/2014-11/6/2019. One Hundred three subjects were enrolled, One Hundred one subjects completed 1-week of medication/placebo, Ninety subjects completed 8-weeks of counseling, and Eighty-four subjects completed a 12-week follow up visit.
Pre-assignment details
Seventy-one subjects were excluded prior to enrollment: sixty-seven did not meet admission criteria and four declined to participate.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Mifepristone 1200 mg Daily 1200 mg mifepristone daily for 1-week given in conjunction with 8 weeks of standardized behavioral therapy
Mifepristone 1200 mg daily: Mifepristone, 300 mg tablets, Four tablets daily/am for 1-week duration.
Standardized behavioral therapy: Standardized behavioral therapy 1 time per week for 8 week duration. | 49 |
| Placebo Daily, 1-week Placebo pills daily for 1-week given in conjunction with 8 weeks of standardized behavioral therapy
. Placebo: Placebo tablets, Four tablets daily/am for 1-week duration.
Standardized behavioral therapy: Standardized behavioral therapy 1 time per week for 8 week duration | 32 |
| Experimental: Mifepristone 600 mg Day 600 mg mifepristone daily for 1-week given in conjunction with 8 weeks of standardized behavioral therapy
Mifepristone 600 mg daily: Mifepristone, 300 mg tablets, Four tablets daily/am (Two 300 mg and two placebo tablets) for 1-week duration.
Standardized behavioral therapy: Standardized behavioral therapy 1 time per week for 8 week duration. | 22 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Experimental: Mifepristone 1200 mg Daily | Placebo Daily, 1-week | Experimental: Mifepristone 600 mg Day | Total |
|---|---|---|---|---|
| Age, Continuous | 46.9 years STANDARD_DEVIATION 11 | 46.4 years STANDARD_DEVIATION 11.9 | 44.4 years STANDARD_DEVIATION 12.3 | 46.2 years STANDARD_DEVIATION 11.5 |
| DSM-V symptom count | 8.63 symptoms STANDARD_DEVIATION 1.53 | 8.22 symptoms STANDARD_DEVIATION 1.99 | 8.59 symptoms STANDARD_DEVIATION 2.3 | 8.5 symptoms STANDARD_DEVIATION 1.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 8 Participants | 4 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 24 Participants | 18 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 4 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 38 Participants | 27 Participants | 17 Participants | 82 Participants |
| Region of Enrollment United States | 49 participants | 32 participants | 22 participants | 103 participants |
| Sex: Female, Male Female | 17 Participants | 13 Participants | 8 Participants | 38 Participants |
| Sex: Female, Male Male | 32 Participants | 19 Participants | 14 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 32 | 0 / 22 |
| other Total, other adverse events | 17 / 49 | 8 / 32 | 2 / 22 |
| serious Total, serious adverse events | 0 / 49 | 1 / 32 | 0 / 22 |
Outcome results
Primary
Drinking Quantity Per Day
Drinking quantity in standard drinks per day is measured by the Timeline Followback interview. A standard drink contains 14 grams of alcohol, e.g., 1.5 ounces of distilled spirits, 5 ounces of wine, or 12 ounces of beer.
Time frame: Participants will be followed for up to 12 weeks post-assignment
Population: Individuals with moderate or greater severity level of alcohol use disorder.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drinking Quantity Per Day | 1.25 Standard drinks per day | Standard Error 0.21 |
| 600 mg/d of Mifepristone | Drinking Quantity Per Day | 1.38 Standard drinks per day | Standard Error 0.21 |
| 1200 mg/d of Mifepristone | Drinking Quantity Per Day | 1.10 Standard drinks per day | Standard Error 0.21 |
p-value: 0.51ANOVA
Comparison: Latent growth model includes one week on study drug and two weeks after the last dose of study drug. Principal predictors were drug plasma concentration and baseline treatment goal of abstinence or non abstinence. Arms were combined for this analysis.p-value: 0.038Mixed Models Analysis
Secondary
Craving
Alcohol Craving Questionnaire; minimum value equals 12, maximum value equals 84; higher scores mean greater craving for alcohol.
Time frame: Participants will be followed for up to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Craving | 29.02 score on a scale | Standard Error 36.69 |
| 600 mg/d of Mifepristone | Craving | 33.66 score on a scale | Standard Error 36.69 |
| 1200 mg/d of Mifepristone | Craving | 28.33 score on a scale | Standard Error 36.69 |
p-value: 0.5ANOVA