Ghrelin for Alcohol Use in Non-Treatment-Seeking Heavy Drinkers

NCT01779024 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 13004313-AA-0043
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

fMRI; Alcohol Drinking; Alcoholism

Keywords

Addiction; Alcohol; Alcohol Clamp

Outcome Measures

Primary Outcomes (1)

• Alcohol Infusions Self-administered

  The total number of alcohol infusions self-administered.

  120 minutes after the start of the infusion

Study Arms (4)

ASA/Ghrelin

EXPERIMENTAL

Intravenous acyl-ghrelin \[a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)\] was administered on the first ASA visit; Intravenous placebo \[packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor\] was administered on the second ASA visit.

Drug: Ghrelin; Drug: Alcohol

ASA/Placebo

PLACEBO COMPARATOR

Intravenous placebo \[packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor\] was administered on the first ASA visit; Intravenous acyl-ghrelin \[a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)\] was administered on the second ASA visit

Drug: Placebo; Drug: Alcohol

fMRI/Ghrelin

EXPERIMENTAL

Intravenous acyl-ghrelin \[a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)\] was administered on the first fMRI visit; Intravenous placebo \[packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor\] was administered on the second fMRI visit.

Drug: Ghrelin; Procedure: fMRI

fMRI/Placebo

PLACEBO COMPARATOR

Intravenous placebo \[packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor\] was administered on the first fMRI visit; Intravenous acyl-ghrelin \[a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)\] was administered on the second fMRI visit

Drug: Placebo; Procedure: fMRI

Interventions

Ghrelin DRUG

ASA/Ghrelin; fMRI/Ghrelin

Placebo DRUG

ASA/Placebo; fMRI/Placebo

fMRI PROCEDURE

fMRI/Ghrelin; fMRI/Placebo

Alcohol DRUG

ASA/Ghrelin; ASA/Placebo

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• Current or prior history of any clinically significant disease, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders.
• 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.

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (9)

• 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. doi: 10.1038/45230.

  PMID: 10604470 BACKGROUND

• Cummings DE, Naleid AM, Figlewicz Lattemann DP. Ghrelin: a link between energy homeostasis and drug abuse? Addict Biol. 2007 Mar;12(1):1-5. doi: 10.1111/j.1369-1600.2007.00053.x. No abstract available.

  PMID: 17407491 BACKGROUND

• 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. doi: 10.1111/j.1369-1600.2006.00002.x.

  PMID: 16759336 BACKGROUND

• 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 Nov 1;76(9):734-41. doi: 10.1016/j.biopsych.2014.03.019. Epub 2014 Mar 25.

  PMID: 24775991 BACKGROUND

• 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.

  PMID: 24090583 BACKGROUND

• 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.

  PMID: 21392177 BACKGROUND

• 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.

  PMID: 20440417 BACKGROUND

• Farokhnia M, Grodin EN, Lee MR, Oot EN, Blackburn AN, Stangl BL, Schwandt ML, Farinelli LA, Momenan R, Ramchandani VA, Leggio L. Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals. Mol Psychiatry. 2018 Oct;23(10):2029-2038. doi: 10.1038/mp.2017.226. Epub 2017 Nov 14.

  PMID: 29133954 RESULT

• Richardson RS, Farokhnia M, Vendruscolo LF, Leggio L. Plasma concentrations of the inflammatory adipokine lipocalin-2 are not affected by chronic alcohol exposure in rats or acute alcohol administration in people with alcohol use disorder. Am J Drug Alcohol Abuse. 2025;51(6):730-740. doi: 10.1080/00952990.2025.2582563. Epub 2025 Dec 2.

  PMID: 41329966 DERIVED

MeSH Terms

Conditions

Alcohol Drinking; Alcoholism; Behavior, Addictive

Interventions

Ghrelin; Ethanol

Condition Hierarchy (Ancestors)

Drinking Behavior; Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Compulsive Behavior; Impulsive Behavior

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Alcohols; Organic Chemicals

Results Point of Contact

• Title: Leggio, Lorenzo
• Organization: National Institute on Alcohol Abuse and Alcoholism

lorenzo.leggio@nih.gov

+1 301 435 9398

Study Officials

• Lorenzo Leggio, M.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2013
• First Posted: January 29, 2013
• Study Start: December 13, 2012
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: August 3, 2018
• Results First Posted: August 3, 2018

Record last verified: 2017-06-01

Locations

US (1)