Alcohol Use Disorder
Conditions
Brief summary
The primary hypotheses under test are that alcohol dependent subjects treated with apremilast 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
DRUGApremilast
Fixed oral dose of 90 mg/d following the standard titration for a total dosing duration of 14 days.
DRUGPlacebo
Identical placebo pills taken orally for 14 days
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female volunteers, 18-65 years of age * Meets DSM-5 criteria for current alcohol use disorder of moderate or greater severity (AUD-MS) * In the month prior to screening, reports drinking ≥ 21 standard drinks per week if male, ≥ 14 if female, with at least one heavy drinking day (≥ 5 males, ≥ 4 females) per week. * 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 * Negative BAC and a CIWA score of \< 9 at time of lab session to eliminate acute alcohol or withdrawal effects on dependent measures. * In acceptable health in the judgment of the study physician, on the basis of interview, medical history, physical exam, EKG, routine urine and blood chemistry. * Females with childbearing potential must have a negative pregnancy test on the screening, randomization, and lab session visits and agree to use effective birth control for the duration required by a given study. * Able to provide informed consent and understand questionnaires and study procedure * Willing to comply with the provisions of the protocol and take daily oral medication.
Exclusion criteria
* Active suicidal ideation, as systematically assessed with the Columbia Suicide Severity Rating Scale. * Meets DSM-5 criteria for a major psychiatric disorder, including mood or anxiety disorders or substance use disorders other than alcohol or nicotine * Has a urine drug screen (UDS) positive for substances of abuse other than alcohol. * Significant medical disorders that will increase potential risk or interfere with study participation as determined by the study physician * Known hypersensitivity to apremilast * Treatment within the month prior to screening with (1) an investigational drug, (2) medications which may negatively interact with study medications, or (3) drugs that may influence study outcomes (e.g., disulfiram \[Antabuse\], naltrexone \[ReVia\], acamprosate \[Campral\], anticonvulsants, or antidepressants). * Ongoing treatment with medications that may increase risk, including prescribed, over-the-counter, and herbal preparations, as determined by the study physician. * Sexually active female subjects with childbearing potential who are pregnant, nursing, or refuse to use effective methods of birth control for the duration required by a specific protocol. * No fixed domicile and/or no availability by home or mobile telephone * History of hypersensitivity to the study drug or the ingredients. * Failure to take double-blind medication as prescribed.
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 accessed during the 11 days of ad libidum and did not include the final three days of mandatory abstinence prior to cue reactivity testing on day 14 of dosing.) | 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 accessed during the 11 days of ad libidum and did not include the final three days of mandatory abstinence prior to cue reactivity testing on day 14 of dosing. |
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 11/01/2017-04/01/2020. Seventy-seven non-treatment seeking, paid volunteers signed informed consent, Fifty-one subjects were enrolled, and Forty-three subjects completed the study.
Pre-assignment details
Twenty-six subjects were excluded from study participation, twenty-two did not meet admission criteria and four declined to participate.
Participants by arm
| Arm | Count |
|---|---|
| Apremilast (Otezla) Fixed oral dose of 90 mg/d following the standard titration for a total dosing duration of 14 days. | 26 |
| Placebo Placebo pill taken orally for 14 days | 25 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Medication non-compliance | 2 | 2 |
Baseline characteristics
| Characteristic | Apremilast (Otezla) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 39.12 years STANDARD_DEVIATION 13.9 | 43.3 years STANDARD_DEVIATION 18.5 | 41.16 years STANDARD_DEVIATION 16.3 |
| DSM-V symptom count | 6.58 Symptom count STANDARD_DEVIATION 2.2 | 6.24 Symptom count STANDARD_DEVIATION 2.4 | 6.41 Symptom count STANDARD_DEVIATION 2.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 20 Participants | 44 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 4 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 | 20 Participants | 23 Participants | 43 Participants |
| Region of Enrollment United States | 26 participants | 25 participants | 51 participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 11 Participants | 16 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 25 |
| other Total, other adverse events | 22 / 26 | 19 / 25 |
| serious Total, serious adverse events | 0 / 26 | 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) |
|---|---|---|
| Apremilast (Otezla) | Craving to Drink | 33.84 score on a scale |
| Placebo | Craving to Drink | 28.31 score on a scale |
p-value: 0.3695% CI: [-10.22, 29.38]Mixed 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 accessed during the 11 days of ad libidum and did not include the final three days of mandatory abstinence prior to cue reactivity testing on day 14 of dosing.
Time frame: 11 days (Treatment effects on drinking were accessed during the 11 days of ad libidum and did not include the final three days of mandatory abstinence prior to cue reactivity testing on day 14 of dosing.)
Population: All subjects with post baseline drinking data were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Apremilast (Otezla) | Drinking | 3.71 Drinks per day | Standard Error 0.82 |
| Placebo | Drinking | 3.92 Drinks per day | Standard Error 0.82 |
Comparison: Posted results show mean change in drinking for the drug group relative to placebo for each day of the 11 days of ad libidum drinking (Days 1-11) permitted during the 14 days (2 weeks) of medication.p-value: <0.025t-test, 2 sided
p-value: 0.025Mixed Models Analysis