Alcohol Use Disorder (AUD), Healthy Volunteers
Conditions
Keywords
Suvorexant, Sleep, Dopamine D2R, Dopamine D1R, Alcohol Use Disorder (AUD), Alcohol Craving
Brief summary
Background: Alcohol use disorder (AUD) is a leading cause of disease and death worldwide. New treatments for AUD are needed. Dopamine, a chemical that carries signals between brain cells, is thought to play a role in alcohol addiction. Researchers want to learn how Suvorexant, a drug used to treat sleep disorders, affects dopamine receptors in the brain. Objective: To see how Suvorexant affects dopamine receptors in people with AUD and in healthy people. Eligibility: People aged 18 to 75 years seeking treatment for AUD. Healthy volunteers are also needed. Design: Participants with AUD will stay in the clinic for at least 10-28 days for alcohol detoxification. They will receive normal treatment for AUD. Suvorexant is a medicine used to treat sleep problem that is taken taken by mouth, once a day. Some participants will take the study drug. Others will take a placebo. The placebo looks like the study drug but does not contain any medicine. Participants will not know which they are taking. Participants will wear a device that looks like a wristwatch to track their movements during their clinic stay. Participants will have blood tests and 3 brain imaging scans before starting on the study drug: 2 positron emission tomography (PET) and 1 magnetic resonance imaging (MRI) scan. They will be injected with a radioactive tracer during each PET scan. Participants will have tests to assess their thinking, memory, and attention. They will have sleep studies. Imaging scans and other tests will be repeated at the end of the study. Healthy volunteers will have 1 MRI and 2 PET scans. They will have tests to assess of their thinking, memory, and attention. They will wear a wristwatch like movement monitor for 1 week. ...
Detailed description
Study Description: This protocol examines effects of a 10-28 day course of suvorexant treatment on brain dopamine receptors, brain reactivity to cues and symptomatology in individuals with alcohol use disorder (AUD) undergoing detoxification. We hypothesize that suvorexant compared to placebo will (1) increase striatal dopamine D2 receptors while decreasing the balance of D1 to D2 receptor signaling (D1R/D2R) and (2) improve sleep and reduce alcohol craving and dysphoria. Objectives: Primary objectives: To examine the impact of suvorexant on dopamine receptors in adults with AUD undergoing detoxification and to compare against baseline measures in healthy controls. Secondary objectives: To examine suvorexant's effects on sleep quality and alcohol craving in adults with AUD undergoing detoxification. Endpoints: Primary Endpoint: Suvorexant's effects on brain dopamine receptors: -Striatal dopamine D1 and D2 receptor availabilities and D1R/D2R ratios Secondary Endpoints: Effects of suvorexant on: * N3, REM, and total sleep duration (assessed with polysomnography) * Self-reports of sleep quality * Self-reports of alcohol craving and mood Exploratory Endpoints: * Brain structure, function, chemistry and cerebrospinal fluid (CSF) dynamics as assessed by MRI (task and resting fMRI, MRS, structural MRI, and diffusion tensor imaging or DTI) * Cognitive Test Performance
Interventions
DRUGPlacebo
The placebo will be a tablet, but only containing inert inactive ingredients.
DRUGSuvorexant
Drug approved for improving sleep
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA: * All Participants To be eligible to participate in this study, an individual must meet all of the following criteria: * Stated willingness to comply with all study procedures and availability for the duration of the study. * Male or female, ages 18-75 years old. * Ability to understand and the willingness to sign a written informed consent document. * AUD Participants To be eligible to participate in this study, an individual with AUD must meet all of the "All Participants" inclusion criteria (listed above) and also meet the following criteria: * DSM 5 diagnosis of moderate or severe AUD. * Participants seeking treatment for their AUD. * Current AUD with minimum 5-year lifetime history of heavy drinking (SAMSHA's criteria for heavy drinking: for men 5 or more drinks/day on at least 5 different days per month; and for women 4 or more drinks/day on at least 5 different days per month). * Last alcohol use within the 7 days prior to enrollment in the Natural History protocol 14AA0181. * Self-reported insomnia/sleep problems: PSQI score \> 4 and/or endorsing "problems falling asleep or staying asleep throughout the night". * Ability to take oral medication and be willing to adhere to the suvorexant/placebo regimen. * Agreement to commit to at least 28 days, and up to 40 days, inpatient stay (starting from Natural History protocol enrollment). * Agreement to adhere to Lifestyle Considerations throughout study duration.
Exclusion criteria
-All Participants An individual who meets any of the following criteria will be excluded from participation: * Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head, fear of enclosed spaces, or other standard contraindication to MRI. * Cannot lie comfortably flat on his/her back for up to 2 hours in the MRI scanner. * Body weight \> 400 lbs. The PET scanner bed is tested to a weight limit of 400 lbs. * Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that, with the exposure from this study, would exceed NIH annual research limits as determined by medical history and physical exam. * Pregnant or breast-feeding: Females of childbearing potential, or with tubal ligation, or are post-menopausal and are age 55 or less will undergo a urine pregnancy test and it must be negative to continue participation. Urine pregnancy tests will be repeated on subsequent days of study (i.e., within 24 hours before study procedures). Females must not be currently breastfeeding. * Severe head trauma with loss of consciousness \> 60 minutes. * Chronic recurrent primary psychotic disorders like schizophrenia and bipolar 1 disorder. * Montgomery-Asberg depression rating scale (MADRS) total score \> 35 or 'suicidal thoughts' item score \> 3, indicating severe depression or moderate suicidality, respectively. * Major medical problems that can permanently impact brain function (e.g., seizures, psychosis, stroke, Alzheimer's disease, Parkinson's disease, traumatic brain injury, clinically significant arrhythmias except bradycardia, and HIV+). * Hepatic enzymes (ALT/GPT, AST/GOT, Total Bilirubin, Direct Bilirubin) that are \>5x the upper limit of normal, indicating severe hepatic impairment. * Non-English speakers (must also be able to read and comprehend English). * The intent of the research has no prospect of direct benefit to the subject. Therefore, we are excluding non-English speakers in this research study since it includes the administration of questionnaires, surveys and assessments that are validated for English; only some are available in Spanish. In addition, our fMRI paradigms require that the subject be able to speak, read and comprehend English. * AUD Participants An individual with AUD who meets any of the "All Participants"
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To examine the impact of suvorexant on dopamine receptors in adults with AUD undergoing detoxification and to compare against baseline measures in healthy controls. | 3 years | We hypothesize that suvorexant compared to placebo will (1) increase striatal dopamine D2 receptors while decreasing the balance of D1 to D2 receptor signaling (D1R/D2R) and (2) improve sleep and reduce alcohol craving and dysphoria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To examine suvorexant's effects on sleep quality and alcohol craving in adults with AUD undergoing detoxification. | 3 years | We hypothesize that suvorexant compared to placebo will improve sleep and reduce alcohol craving and dysphoria. |
Countries
United States
Contacts
CONTACTMichele-Vera I Yonga, C.R.N.P.
CONTACTNora D Volkow Adler, M.D.
PRINCIPAL_INVESTIGATORNora D Volkow Adler, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Outcome results
None listed