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Protocol Details

Effects of ghrelin on Alcohol Administration in Non-Treatment Seeking Heavy Drinkers

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

13-AA-0043

Sponsoring Institute

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 21
Max Age: 60

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Addiction;
Alcohol;
Alcohol Clamp

Recruitment Keyword(s)

None

Condition(s)

fMRI;
Alcohol Drinking;
Alcoholism

Investigational Drug(s)

ghrelin and Alcohol

Investigational Device(s)

None

Intervention(s)

Drug: ghrelin
Drug: Placebo
Procedure/Surgery: fMRI
Drug: Alcohol

Supporting Site

National Institute on Alcohol Abuse and Alcoholism

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.

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Eligibility

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 or equal 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.


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Citations:

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999 Dec 9;402(6762):656-60

Cummings DE, Naleid AM, Figlewicz Lattemann DP. ghrelin: a link between energy homeostasis and drug abuse? Addict Biol. 2007 Mar;12(1):1-5.

Jerlhag E, Egecioglu E, Dickson SL, Andersson M, Svensson L, Engel JA. ghrelin stimulates locomotor activity and accumbal dopamine-overflow via central cholinergic systems in mice: implications for its involvement in brain reward. Addict Biol. 2006 Mar;11(1):45-54.

Leggio L, Zywiak WH, Fricchione SR, Edwards SM, de la Monte SM, Swift RM, Kenna GA. Intravenous ghrelin Administration Increases Alcohol Craving in Alcohol-Dependent Heavy Drinkers: A Preliminary Investigation. Biol Psychiatry. 2014 Mar 25. pii: S0006-3223(14)00220-0. doi: 10.1016/j.biopsych.2014.03.019. [Epub ahead of print]

Leggio L, Schwandt ML, Oot EN, Dias AA, Ramchandani VA. Fasting-induced increase in plasma ghrelin is blunted by intravenous alcohol administration: a within-subject placebo-controlled study. Psychoneuroendocrinology. 2013 Dec;38(12):3085-91. doi: 10.1016/j.psyneuen.2013.09.005. Epub 2013 Sep 13.

Leggio L, Ferrulli A, Cardone S, Nesci A, Miceli A, Malandrino N, Capristo E, Canestrelli B, Monteleone P, Kenna GA, Swift RM, Addolorato G. ghrelin system in alcohol-dependent subjects: role of plasma ghrelin levels in alcohol drinking and craving. Addict Biol. 2012 Mar;17(2):452-64. doi: 10.1111/j.1369-1600.2010.00308.x. Epub 2011 Mar 11.

Leggio L. Role of the ghrelin system in alcoholism: Acting on the growth hormone secretagogue receptor to treat alcohol-related diseases. Drug News Perspect. 2010 Apr;23(3):157-66. doi: 10.1358/dnp.2010.23.3.1429490.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Lorenzo Leggio, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
BG 10-CRC RM 1-5429
10 CENTER DR
BETHESDA MD 20814
(301) 435-9398
lorenzo.leggio@nih.gov

Lorenzo Leggio, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
BG 10-CRC RM 1-5429
10 CENTER DR
BETHESDA MD 20814
(301) 435-9398
lorenzo.leggio@nih.gov

Patient Recruitment and Public Liaison Office
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Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

prpl@mail.cc.nih.gov

Clinical Trials Number:

NCT01779024

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