Ghrelin for Alcohol Use in Non-Treatment-Seeking Heavy Drinkers
Condition: fMRI; Alcohol Drinking; Alcoholism
MeSH terms: Alcoholism; Alcoholic Intoxication; Alcohol Drinking
Intervention: Ghrelin; Placebo; fMRI; Alcohol
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 17.0
Sex: All
Minimum age: 21 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Addiction; Alcohol; Alcohol Clamp

Summary:

      Background:

      - Ghrelin is a hormone in the human body that is mostly produced by the stomach. It makes
      people feel hungry, and also is connected with the desire to drink alcohol. Researchers want
      to test ghrelin to see if it can be used to control alcohol cravings and use. They will
      compare doses of ghrelin with a placebo in people who drink heavily.

      Objectives:

      - To study the effects of ghrelin on alcohol craving and use.

      Eligibility:

        -  Individuals between 21 and 60 years of age who are heavy drinkers but are not seeking
           treatment for alcohol use.

        -  Participants must on average have more than 20 drinks per week for men, and more than 15
           drinks per week for women.

      Design:

        -  Participants will have a screening visit, four 2-night study visits, and a follow-up
           visit.

        -  Participants will be screened with a physical exam and medical history. They will
           provide urine and breath samples for drug testing. They will also answer questions about
           mood and physical symptoms, and about alcohol and other cravings.

        -  At the study visits, participants will stay overnight at the National Institutes of
           Health clinical center. They will spend the night at the center, have tests on the next
           day, and go home on the following morning. At each visit, participants will receive a
           ghrelin or placebo infusion, and will complete a series of tasks.

        -  For the first and second study visits, participants will have tests of alcohol craving
           and use. They will be able to receive alcohol infusions through a computer program that
           tests response time and craving reactions. At the same time, they will have a ghrelin or
           a placebo infusion. Blood alcohol levels, reaction time, and craving will be studied.

        -  For the third and fourth study visits, participants will have a magnetic resonance
           imaging (MRI) study. They will have an initial MRI to provide a picture of the brain.
           They will then have a functional MRI during which they will respond to a computer test.
           The test will allow them to win points for snack food or alcohol. This test will look at
           the brain s response time and craving reactions.

        -  There will be a follow-up visit 1 week after the fourth study visit. Some of the tests
           from the screening visit will be repeated.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Male and female participants between 21-60 years of age.

        Good health as determined by medical history, physical exam, ECG and lab tests.

        Creatinine less than to 2 mg/dl.

        Female must have a negative urine pregnancy (hCG) test at the start of each study session.
        Females of childbearing potential who are sexually active and have not been surgically
        sterilized must agree to use an adequate method of birth control during the study. Adequate
        methods of contraception for sexually active women are having a male sexual partner(s) who
        is surgically sterilized prior to inclusion; having a sexual partner(s) who is/are
        exclusively female; using oral contraceptives (either combined or progestrogen only) with a
        single-barrier method of contraception consisting of spermicide and condom or diaphragm;
        using double-barrier contraception, specifically, a condom plus spermicide and a female
        diaphragm or cervical cap plus spermicide; or using an approved intrauterine device (IUD)
        with established efficacy.

        Participants must drink alcohol regularly at a heavy level, on average greater than 20
        drinks per week for men, and greater than 15 drinks per week for women, and not be seeking
        help for alcohol-related problems.

        Participant must be willing to receive two IV lines.

        EXCLUSION CRITERIA:

        Current or prior history of any clinically significant disease, including CNS,
        cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive
        disorders.

        Specific exclusion criteria related to the administration of ghrelin, are chronic
        inflammatory diseases (e.g., Crohn s disease, ulcerative colitis, celiac disease) diabetes,
        obesity (BMI greater than or equal 30 kg/m(2), weight greater than or equal to 120 Kg, high
        triglycerides level (> 350 mg/dL), history of clinically significant hypotension (e.g.:
        history of fainting and/or syncopal attacks) and/or resting systolic BP < 100 mmHg.

        Positive hepatitis or HIV test at screening.

        Current clinically significant major depression or anxiety; or prior clinically significant
        psychiatric problems, including eating disorders, schizophrenia, bipolar disorder,
        obsessive compulsive disorder.

        Current diagnosis of substance dependence (other than alcohol or nicotine).

        Currently seeking treatment for alcohol use disorder.

        History of significant withdrawal symptoms or presence of clinically significant withdrawal
        symptoms (Clinical Institute Withdrawal Assessment (CIWA) score > 8) at screening.

        Non-drinkers (alcohol-naive individuals or current abstainers) or no experience drinking 5
        or more drinks on one occasion.

        Unable to provide a negative urine drug screen.

        Pregnancy or intention to become pregnant for women. Female participants will undergo a
        urine beta-hCG test to ensure they are not pregnant.

        Use of prescription or OTC medications known to interact with alcohol within 2 weeks of the
        study. These include, but may not be limited to: isosorbide, nitroglycerine,
        benzodiazepines, warfarin, anti-depressants such as amitriptyline, clomipramine and
        nefazodone, anti-diabetes medications such as glyburide, metformin and tolbutamide,
        H2-antagonists for heartburn such as cimetidine and ranitidine, muscle relaxants,
        anti-epileptics including phenytoin and Phenobarbital codeine, and narcotics including
        darvocet, percocet and hydrocodone. Drugs known to inhibit or induce enzymes that
        metabolize alcohol should not be used for 4 weeks prior to the study. These include
        chlorzoxazone, isoniazid, metronidazole and disulfiram. Cough-and-cold preparations, which
        contain antihistamines, pain medicines and anti-inflammatories such as aspirin, ibuprofen,
        acetaminophen, celecoxib and naproxen, should be withheld for at least 72 hours prior to
        each study session.

        Current or prior history of alcohol-induced flushing reactions.

        Contraindications for MRI scanning, including metal in body that are contraindicated for
        MRI (such as implants, pacemaker, prostheses, shrapnel, irremovable piercings),
        left-handedness, and claustrophobia.