Alcohol Use Disorder
Conditions
Keywords
Alcohol-Related Disorders
Brief summary
The hypotheses under test are that subjects with alcohol use disorder (AUD) of moderate or greater severity treated with CORT118335 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
DRUGMiricorilant
900 mg (6 x 150 mg) tablets taken orally once daily for two weeks
DRUGPlacebo oral tablet
Six placebo tablets taken orally once daily for two weeks
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
The Scripps Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Parallel Assignment, Double-Blind, Randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female volunteers, 18-75 years of age. * Meets DSM-5 criteria for current alcohol use disorder of moderate or greater severity (AUD-MS). * Subjects will not be seeking treatment because the medication studies are not treatment trials, and to avoid exposing treatment-seekers to alcohol cues. * Subjects must be abstinent a minimum of 3 days (but not more than 7 days) prior to the human lab session. * In acceptable health in the judgment of the study physician, based on interview, medical history, physical exam, ECG, routine urine and blood chemistry. * Subjects with a history of depression, who have been on a stable dose of anti-depressant medication for at least 3 months, and do not meet current DSM-5 criteria for depression or anxiety. * All subjects must agree to use double barrier birth control for the study duration and one month thereafter i.e., males must use condoms and females must use spermicide and/or a non hormonal barrier method, and their opposite sex partner must likewise use an effective non hormonal form of contraception. * Able to provide informed consent and understand questionnaires and study procedures in English. * Willing to comply with the provisions of the protocol and take daily oral medication
Exclusion criteria
* Medical conditions that could be aggravated by glucocorticoid and/or mineralocorticoid antagonism. * Clinically significant findings on physical exam, ECG, urine or blood tests that may increase risk. * CYP2C19 inhibitors * Substrates metabolized primarily by CYP3A, CYP2C9, and CYP2C8 with narrow therapeutic index * BCRP and UGT1A1 substrates * Meets DSM-5 criteria for a current major psychiatric disorder, including mood, anxiety or substance use disorders, other than alcohol, nicotine, or mild cannabis use disorders. * Pregnant or lactating. * Treatment within the month prior to screening with (1) an investigational drug, (2) drugs which may negatively interact with study medications, or (3) drugs that may influence study outcomes (e.g., disulfiram \[Antabuse\], naltrexone \[ReVia\], acamprosate \[Campral\], or anticonvulsants. * Chronic systemic steroid use * Using drugs that are strong inhibitors and inducers of CYP2C9. * No fixed domicile and/or no availability by home or mobile telephone.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Craving to Drink | 1 hour on the last day of dosing (Day 14) | Total 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 | 11 days (Treatment effects on drinking were assessed during the 11 days of ad libitum drinking) | Number of standard drinks per day using the Timeline Followback Interview (TLFB). Total number of alcoholic drinks consumed per day with a minimum value of 0 and an undetermined maximum value. Treatment effects on drinking were assessed during the 11 days of ad libitum drinking and did not include the final three days of mandatory abstinence prior to cue reactivity session. |
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 04/15/2021-05/25/2022. Seventy-seven non-treatment seeking, paid volunteers signed informed consent, Fifty subjects were enrolled, and Fifty subjects completed the study.
Pre-assignment details
Twenty-seven subjects were excluded from study participation, twenty-five did not meet admission criteria and two declined to participate.
Participants by arm
| Arm | Count |
|---|---|
| CORT118335 900 mg (6 x 150 mg) tablets daily taken orally for two weeks
CORT118335: 900 mg (6 x 150 mg) tablets taken orally once daily for two weeks | 25 |
| Placebo Six placebo tablets taken orally for two weeks
Placebo oral tablet: Six placebo tablets taken orally once daily for two weeks | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | CORT118335 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 41.04 years STANDARD_DEVIATION 12.9 | 43.56 years STANDARD_DEVIATION 15 | 42.3 years STANDARD_DEVIATION 28.56 |
| DSM-V symptom count | 6.56 Symptom count STANDARD_DEVIATION 1.9 | 6.56 Symptom count STANDARD_DEVIATION 1.5 | 6.56 Symptom count STANDARD_DEVIATION 1.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 20 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 21 Participants | 39 Participants |
| Region of Enrollment United States | 25 participants | 25 participants | 50 participants |
| Sex: Female, Male Female | 15 Participants | 11 Participants | 26 Participants |
| Sex: Female, Male Male | 10 Participants | 14 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 9 / 25 | 4 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Craving to Drink
Total 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 hour on the last day of dosing (Day 14)
Population: All subjects who completed cue exposure testing in the laboratory were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CORT118335 | Craving to Drink | 31.1 score on a scale |
| Placebo | Craving to Drink | 33.2 score on a scale |
Comparison: Mixed effect model with directional hypothesis that drug reduces strength of craving (VAS). Principle predictor was drug plasma concentration. Arms were combined for this analysis.p-value: 0.065Mixed Models Analysis
Secondary
Drinking
Number of standard drinks per day using the Timeline Followback Interview (TLFB). Total number of alcoholic drinks consumed per day with a minimum value of 0 and an undetermined maximum value. Treatment effects on drinking were assessed during the 11 days of ad libitum drinking and did not include the final three days of mandatory abstinence prior to cue reactivity session.
Time frame: 11 days (Treatment effects on drinking were assessed during the 11 days of ad libitum drinking)
Population: All subjects with post baseline drinking data were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CORT118335 | Drinking | 3.7 Average drinks per day | Standard Error 0.41 |
| Placebo | Drinking | 3.7 Average drinks per day | Standard Error 0.29 |