Alcohol Use Disorder (AUD)
Conditions
Brief summary
The primary hypotheses under test are that alcohol dependent subjects treated with suvorexant 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. Suvorexant (Belsomra®) received approval by the FDA in 2014 for treatment of insomnia. To control for any effect of pre-existing sleep disturbance for which suvorexant may be indicated, subjects will be stratified on the basis of a Pittsburgh Sleep Quality Index total score of \> 5 versus \<5. Subjects were also stratified by sex.
Interventions
DRUGSuvorexant 20 mg
Single-dose administration of 20 mg suvorexant given on an inpatient clinical research unit
DRUGPlacebo oral tablet
Single-dose administration of placebo given on an inpatient clinical research unit
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 Stratified at randomization based on sex and Pittsburgh Sleep Quality Index Total Score (PSQI) greater than or equal to 5 versus less than 5.
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, 5th Edition (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 blood alcohol content (BAC) and a Clinical Institute Withdrawal Assessment (CIWA) score of \< 9 at time of randomization and 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. * 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. * Females with childbearing potential must have a negative pregnancy test on the screening and randomization 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 procedures in English. * Willing to comply with the provisions of the protocol and take oral medication.
Exclusion criteria
* Meets DSM-5 criteria for a major psychiatric disorder, including mood or anxiety disorders or substance use disorders other than alcohol or nicotine, or, mild cannabis use disorder * Has a urine drug screen (UDS) positive for substances of abuse other than alcohol or marijuana * Significant medical disorders that will increase potential risk or interfere with study participation as determined by the study physician. * Liver function tests more than 3 times the upper limit of normal or elevated bilirubin. * Subjects taking digoxin or CYP3A inhibitors or inducers, metabolism by CYP3A is the major elimination pathway for suvorexant. * 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 \[Campral\], or anticonvulsants). * 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 of the study. * 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 |
|---|---|---|
| Visual Analogue Scale (VAS) of Craving Severity: 2 Arms | 1 hour during cue reactivity session | VAS to alcohol cues minus VAS to water cues on a 0-20 VAS scale. Higher scores indicate greater craving strength with a minimum score of 0 and a maximum score of 20. |
| Visual Analog Scale (VAS) Strength of Craving: Combined Arms Conditional Model | 1 hour during cue reactivity session | VAS to alcohol cues minus VAS to water cues on a 0-20 VAS scale. Higher scores indicate greater craving strength with a minimum score of 0 and a maximum score of 20. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Standard Drinks Per Day: 2 Arms | Up to one week following single dose administration | Number of standard drinks per day using the Timeline Followback Interview (TLFB). Total number of alcohol drinks consumed per day with a minimum value of 0 and an undetermined maximum value |
| Number of Standard Drinks Per Day: Combined Arms Conditional Model | Up to one week following single dose administration | 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. |
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, California from 09/30/2021-11/08/2022.
Pre-assignment details
Thirty-two subjects did not meet admission criteria and 12 subjects declined participation.
Participants by arm
| Arm | Count |
|---|---|
| Belsomra,(Suvorexant) 20 mg single-dose administration given on an inpatient clinical research unit
Suvorexant 20 mg: Single-dose administration of 20 mg suvorexant given on an inpatient clinical research unit | 14 |
| Placebo, (Sugar Pill) Placebo single-dose administration given on an inpatient clinical research unit
Placebo oral tablet: Single-dose administration of placebo given on an inpatient clinical research unit | 12 |
| Total | 26 |
Baseline characteristics
| Characteristic | Belsomra,(Suvorexant) | Placebo, (Sugar Pill) | Total |
|---|---|---|---|
| Age, Continuous | 36.29 years STANDARD_DEVIATION 11.7 | 38.83 years STANDARD_DEVIATION 11 | 37.46 years STANDARD_DEVIATION 11.2 |
| DSM-V symptom Count | 6.43 symptom count STANDARD_DEVIATION 2.1 | 8.08 symptom count STANDARD_DEVIATION 2 | 7.19 symptom count STANDARD_DEVIATION 2.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 9 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 9 Participants | 8 Participants | 17 Participants |
| Region of Enrollment United States | 14 Participants | 12 Participants | 26 Participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 12 |
| other Total, other adverse events | 8 / 14 | 7 / 12 |
| serious Total, serious adverse events | 0 / 14 | 0 / 12 |
Outcome results
Primary
Visual Analog Scale (VAS) Strength of Craving: Combined Arms Conditional Model
VAS to alcohol cues minus VAS to water cues on a 0-20 VAS scale. Higher scores indicate greater craving strength with a minimum score of 0 and a maximum score of 20.
Time frame: 1 hour during cue reactivity session
Population: All randomized subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Belsomra,(Suvorexant) | Visual Analog Scale (VAS) Strength of Craving: Combined Arms Conditional Model | .94 score on a scale |
Comparison: Mixed effect model with directional hypothesis that drug reduces strength of craving (VAS). Principle predictors were drug condition, and baseline sleep disturbance (Pittsburgh Sleep Quality Index {PSQI} total score less than 5 or 5 and greater). Arms were combined for this analysis.p-value: 0.007Mixed Models Analysis
Primary
Visual Analogue Scale (VAS) of Craving Severity: 2 Arms
VAS to alcohol cues minus VAS to water cues on a 0-20 VAS scale. Higher scores indicate greater craving strength with a minimum score of 0 and a maximum score of 20.
Time frame: 1 hour during cue reactivity session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belsomra,(Suvorexant) | Visual Analogue Scale (VAS) of Craving Severity: 2 Arms | 2.38 score on a scale | Standard Error 0.9 |
| Placebo | Visual Analogue Scale (VAS) of Craving Severity: 2 Arms | 1.44 score on a scale | Standard Error 0.62 |
Secondary
Number of Standard Drinks Per Day: 2 Arms
Number of standard drinks per day using the Timeline Followback Interview (TLFB). Total number of alcohol drinks consumed per day with a minimum value of 0 and an undetermined maximum value
Time frame: Up to one week following single dose administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belsomra,(Suvorexant) | Number of Standard Drinks Per Day: 2 Arms | 3.59 Standard drinks per day | Standard Error 0.87 |
| Placebo | Number of Standard Drinks Per Day: 2 Arms | 3.46 Standard drinks per day | Standard Error 0.88 |
Secondary
Number of Standard Drinks Per Day: Combined Arms Conditional Model
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.
Time frame: Up to one week following single dose administration
Population: Of the 26 subjects randomized, all 17 subjects that had any follow up drinking data were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Belsomra,(Suvorexant) | Number of Standard Drinks Per Day: Combined Arms Conditional Model | -1.52 number of standard drinks per day |
Comparison: Mixed effect model with directional hypothesis that drug reduces number of drinks per day. Principle predictors were drug condition and sex. Arms were combined for this analysis.p-value: 0.0025Mixed Models Analysis