Overview

Background

Alcohol use disorder (AUD) is a problematic pattern of alcohol use accompanied by clinically significant medical consequences. Medications can help most people reduce their drinking, but the number is limited, and additional treatment options are needed.

Objective

To test if a medication named Semaglutide is safe and may reduce alcohol drinking in people with AUD.

Who can participate?

All Adults aged 18 or older with AUD might be eligible to participate in the study.

What will happen during the study?

Participants will visit the National Institute on Drug Abuse (NIDA) in Baltimore once a week for about 20 weeks (5 months). Each visit will last between 2 and 6 hours depending on the tasks scheduled for that visit.

Participants will be assigned by chance (like flipping a coin) to receive either Semaglutide or placebo. A placebo looks just like a real drug but contains no medicine.

The study medication is given as a shot under the skin each week.

Participants will undergo different tests throughout the study:

They will give blood, urine, and saliva samples.

They will engage in self-paced behavioral therapy on a computer.

They will answer questions about their mood, diet, alcohol drinking and craving, tobacco use, etc.

They will taste several sweet liquids and tell their preferences.

They will sit in a bar-like room and be exposed to cues that might make them feel the urge to eat food or drink alcohol.

They will wear a virtual reality headset that creates a cafeteria setting. They will walk the virtual cafeteria and choose food and drinks from a buffet.

They will have a functional magnetic resonance imaging (fMRI) scan to take pictures of their brain. During the scans, participants will be shown pictures of alcohol-containing drinks, food, and other items.They will perform tasks on a computer screen.

Participants will have a follow-up visit about 7 weeks after their last shot.

Eligibility

• INCLUSION CRITERIA:

        This study will enroll adult individuals with a current diagnosis of AUD. Participants will
        be recruited without any preference to gender, race, religion, or other social variables,
        but sociodemographic data will be collected for sample characterization and potential use
        in the analyses. Since self-reported psychological measures that have been validated in
        English constitute major part of the study assessments, participants need to be able to
        speak, read, write, and understand English to be in the study.
        The information needed to assess eligibility will be collected under an IRB-approved NIDA
        IRP
        screening protocol, led by the Office of the Clinical Director (OCD) at the NIDA IRP to
        assess
        potential research participants eligibility for entering clinical protocols. Additional
        details can be found in the NIDA screening protocol documents. Furthermore, NIH medical
        records (from other NIH clinical protocols) and outside medical records may also be used,
        if available, to determine whether participants fulfill the eligibility criteria.
        To be eligible for this study, an individual must meet all of the following criteria:
          -  At least 18 years old
          -  Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool, e.g., the
             Mini-International Neuropsychiatric Interview (MINI) or the Structured Clinical
             Interview for DSM Disorders (SCID))
          -  Self-reported drinking, according to alcohol TimeLine FollowBack (TLFB), of > 7 drinks
             per week for females or > 14 drinks per week for males during the 28-day period prior
             to screening + at least four days with > 3 drinks for females or > 4 drinks for males
             during the 28-day period prior to screening
          -  Most recent Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar)
             score < 10
          -  Able to speak, read, write, and understand English as demonstrated by ability to
             understand and sign the NIDA screening protocol consent
          -  Normal or corrected-to-normal (e.g., wearing glasses or contacts) vision and normal or
             corrected-to-normal (e.g., with the use of a hearing aid) hearing
        EXCLUSION CRITERIA:
        An individual who meets any of the following criteria will be excluded from enrolling in
        this study:
          -  BMI < 25 kg/m^2 or BMI >= 50 kg/m^2
          -  Evidence of malnutrition as determined by the Nutrition Risk Screening 2002 (NRS-2002)
          -  Most recent blood tests: creatinine >= 2 mg/dL, eGFR <= 60 mL/min/1.73 m^2,
             triglycerides > 500 mg/dl, ALP > 4(SqrRoot) the upper limit of normal, clinically
             abnormal lipase levels per study clinician
          -  Present diagnosis of diabetes mellitus or blood hemoglobin A1c (HbA1c) >= 6.5 %
          -  Current (within the past 30 days) use of the following medications with glucose
             lowering properties: GLP-1 analogues, sulfonylurea, insulin, metformin,
             thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose
             cotransporter-2 (SGLT-2) inhibitors
          -  Current (within the past 30 days) use of weight-lowering medications
          -  Current (within the past 30 days) use of FDA-approved pharmacotherapy for AUD (oral or
             intramuscular naltrexone, acamprosate, disulfiram)
          -  Current (within the past 30 days) use of medications with known interaction with
             semaglutide
          -  Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine
             Neoplasia syndrome type 2 (MEN 2)
          -  Known ongoing history of alcohol ketoacidosis, gastroparesis, pancreatitis (either
             acute or chronic), pancreatic carcinoma, gallbladder disease, jaundice, Mallory-Weiss
             syndrome (esophageal tears secondary to vomiting), esophageal varices, cirrhosis
          -  Known history of gastric bypass surgery
          -  Known history of prior hypersensitivity reaction to semaglutide, any of the product
             components, or any other GLP-1 analogue
          -  Known history of suicidal attempts (within the past 24 months) or active suicidal
             ideation
          -  Known history of vestibular disorders or clinically significant motion sickness
          -  Known history of clinically significant noise-induced hearing loss or tinnitus
          -  Contraindication(s) for brain fMRI
          -  Unstable cardiovascular conditions (e.g., arrhythmias, clinically significant ECG
             abnormalities)
          -  Physical and/or mental health conditions that are clinically unstable, as determined
             by the study clinicians, including (but not limited to) major depressive disorder or
             generalized anxiety disorder unstable during the past three months or other
             psychiatric conditions (e.g., schizophrenia, bipolar disorder) unstable during the
             past twelve months prior to screening.
          -  Female who is pregnant, breast-feeding, or intends to become pregnant or is of
             child-bearing potential and not using a highly effective contraceptive method
          -  Any other reason or clinical condition that the investigators judge may interfere with
             study participation and/or be unsafe for a participant