fMRIPhase 2NCT01779024
Ghrelin for Alcohol Use in Non-Treatment-Seeking Heavy Drinkers
A Phase 2 study testing Ghrelin, fMRI and Alcohol in people with fMRI and Alcohol Drinking, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- fMRI, Alcohol Drinking, Alcoholism
- What is being tested?
- Ghrelin, fMRI and Alcohol
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Dec 2012to 1 Jun 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Effects of Ghrelin on Alcohol Administration in Non-Treatment Seeking Heavy Drinkers
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.
Read more
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.
Read the detailed description
Objective:
Ghrelin is a 28-amino acid peptide acting as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus (ARC), a region that controls the intake of food and other substances, including alcohol. In addition to the ARC, GHS receptors (GHS-Rs) are also highly expressed in the caudal brain stem, the ventral tegmental area (VTA), hippocampus, substantia nigra, and dorsal and medial raphe nuclei. The expression of the GHS-R in the mesolimbic dopamine (DA) pathway suggests that ghrelin could play a role in reward processing. The role of ghrelin in the DA reward processing and the role of the DA reward system in alcoholism suggest a role of ghrelin in alcoholism. Consistent with this hypothesis, preclinical studies demonstrate that both ghrelin and ethanol activate the cholinergic-dopaminergic reward link, implying neurochemical analogies between ghrelin and ethanol. This supports the hypothesis that ghrelin is involved in mediating the rewarding properties of ethanol. Additional animal experiments demonstrate that the central ghrelin action not only stimulates the reward processing but is also required for stimulation of that system by alcohol. Human studies show reduced ghrelin levels in actively drinking alcoholics; increased ghrelin levels during alcohol abstinence; and a positive correlation between ghrelin level and alcohol craving scores. More recently, a study conducted at Brown University by the PI demonstrated the safety of the administration IV of human ghrelin to non-treatment seeking alcohol-dependent heavy drinking individuals. Furthermore, a preliminary interim analysis shows that IV ghrelin administration may lead to a temporary significant increase in alcohol craving. The primary objective of this protocol is to investigate whether IV ghrelin, as compared to placebo, will increase motivation for alcohol reward, as measured by a progressive ratio (PR) schedule paradigm with IV alcohol self-infusion (primary aim). We will also assess a number of secondary aims. Specifically, we will also assess whether IV ghrelin, as compared to placebo, will also alter urges to drink and the subjective response to IV alcohol. Adverse events will also be assessed to ensure the safety of the IV coadministration of ghrelin and alcohol. During an fMRI/alcohol clamp session, fMRI will be used to see whether ghrelin affects the activation of the ventral striatum induced by acute IV alcohol administration and the incentive salience of cues associated with alcohol administration.
Study Population:
Male and female participants will be non-treatment seeking heavy drinking volunteers.
Design:
The study is designed as a within-subject, double-blind, placebo-controlled study of ghrelin. The first visit will be the initial screening visit. The second and third visits will be PR sessions with IV ethanol, during which each participant will also receive IV ghrelin (or matched placebo). The fourth and fifth visits will combine an fMRI session with an alcohol clamp session (i.e. a fixed dose of alcohol will be administered) and subjects will participate in a modified version of the monetary incentive delay (MID) task in which they will respond to cues that indicate the opportunity to press a button to gain a reward. On some trials the reward will be points that can be exchanged for snack foods while on other trials the reward will be points that will determine how much intravenous alcohol a subject will be given during the alcohol clamp procedure which will immediately follow the modified MID task. After the modified MID task is complete subjects will have a short break and then begin the alcohol IV infusion.
Outcome measures:
The primary measure of this study will be the breakpoint, which is the schedule (number of button presses) at which the individual stops to work for more alcohol. Also, the BrAC exposure measures will be determined. Alcohol craving in response to ghrelin will be measured using the Alcohol Visual Analogue Scale (A-VAS) and the Alcohol Urge Questionnaire (AUQ) during the PR sessions. Sensitivity to alcohol will be measured using the Drug Effects Questionnaire (DEQ), Biphasic Alcohol Effects Scale (BAES), and the Profile of Mood States (POMS), repeatedly during the PR sessions and the CASE Experience Questionnaire (CEQ) at the end of all sessions. fMRI BOLD signal in brain areas associated with incentive salience and areas associated with reward circuitry (including the ventral striatum) will be measured during the fMRI/alcohol clamp session. This study may facilitate the identification of a novel neuropharmacological target, thus facilitating the development of novel pharmacological treatments for alcoholism.
- Conditions
- fMRI, Alcohol Drinking, Alcoholism
- Being tested
- Ghrelin, Placebo, fMRI, Alcohol
- Keywords
- Addiction, Alcohol, Alcohol Clamp
- Medical subject headings
- Alcohol Drinking, Alcoholism, Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GhrelinDrug
PlaceboDrug
fMRIProcedure or surgery
AlcoholDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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. Receives: 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 Receives: Drug: Placebo; Procedure: fMRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alcohol Infusions Self-administered
The total number of alcohol infusions self-administered.
Measured: 120 minutes after the start of the infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2013 (estimated)
- Study start13 Dec 2012
- Primary completion1 Jun 2017
- Study completion1 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for fMRIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lorenzo Leggio, M.D., Principal investigator, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01779024
- Sponsor's protocol ID
- 130043
- Other IDs
- 13-AA-0043
- Status last verified
- 1 Jun 2017
- First submitted
- 24 Jan 2013
- Last updated
- 3 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 10604470Cummings 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.
PubMed 17407491Jerlhag 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.
PubMed 16759336Leggio 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.
PubMed 24775991Leggio 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.
PubMed 24090583Leggio 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.
PubMed 21392177Leggio 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.
PubMed 20440417Farokhnia 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.
PubMed 29133954Richardson 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.
PubMed 41329966
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Ghrelin on Alcohol Administration in Non-Treatment Seeking Heavy Drinkers
- ClinicalTrials.gov ID
- NCT01779024
- Acronym / sponsor ID
- 130043
- Conditions
- fMRI, Alcohol Drinking, Alcoholism
- Keywords
- Addiction, Alcohol, Alcohol Clamp
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Study start
- 13 Dec 2012
- Primary completion
- 1 Jun 2017 (actual)
- Study completion
- 1 Jun 2017 (actual)
- First posted
- 29 Jan 2013 (estimated)
- Results
- Posted 3 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Objective:
Ghrelin is a 28-amino acid peptide acting as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus (ARC), a region that controls the intake of food and other substances, including alcohol. In addition to the ARC, GHS receptors (GHS-Rs) are also highly expressed in the caudal brain stem, the ventral tegmental area (VTA), hippocampus, substantia nigra, and dorsal and medial raphe nuclei. The expression of the GHS-R in the mesolimbic dopamine (DA) pathway suggests that ghrelin could play a role in reward processing. The role of ghrelin in the DA reward processing and the role of the DA reward system in alcoholism suggest a role of ghrelin in alcoholism. Consistent with this hypothesis, preclinical studies demonstrate that both ghrelin and ethanol activate the cholinergic-dopaminergic reward link, implying neurochemical analogies between ghrelin and ethanol. This supports the hypothesis that ghrelin is involved in mediating the rewarding properties of ethanol. Additional animal experiments demonstrate that the central ghrelin action not only stimulates the reward processing but is also required for stimulation of that system by alcohol. Human studies show reduced ghrelin levels in actively drinking alcoholics; increased ghrelin levels during alcohol abstinence; and a positive correlation between ghrelin level and alcohol craving scores. More recently, a study conducted at Brown University by the PI demonstrated the safety of the administration IV of human ghrelin to non-treatment seeking alcohol-dependent heavy drinking individuals. Furthermore, a preliminary interim analysis shows that IV ghrelin administration may lead to a temporary significant increase in alcohol craving. The primary objective of this protocol is to investigate whether IV ghrelin, as compared to placebo, will increase motivation for alcohol reward, as measured by a progressive ratio (PR) schedule paradigm with IV alcohol self-infusion (primary aim). We will also assess a number of secondary aims. Specifically, we will also assess whether IV ghrelin, as compared to placebo, will also alter urges to drink and the subjective response to IV alcohol. Adverse events will also be assessed to ensure the safety of the IV coadministration of ghrelin and alcohol. During an fMRI/alcohol clamp session, fMRI will be used to see whether ghrelin affects the activation of the ventral striatum induced by acute IV alcohol administration and the incentive salience of cues associated with alcohol administration.
Study Population:
Male and female participants will be non-treatment seeking heavy drinking volunteers.
Design:
The study is designed as a within-subject, double-blind, placebo-controlled study of ghrelin. The first visit will be the initial screening visit. The second and third visits will be PR sessions with IV ethanol, during which each participant will also receive IV ghrelin (or matched placebo). The fourth and fifth visits will combine an fMRI session with an alcohol clamp session (i.e. a fixed dose of alcohol will be administered) and subjects will participate in a modified version of the monetary incentive delay (MID) task in which they will respond to cues that indicate the opportunity to press a button to gain a reward. On some trials the reward will be points that can be exchanged for snack foods while on other trials the reward will be points that will determine how much intravenous alcohol a subject will be given during the alcohol clamp procedure which will immediately follow the modified MID task. After the modified MID task is complete subjects will have a short break and then begin the alcohol IV infusion.
Outcome measures:
The primary measure of this study will be the breakpoint, which is the schedule (number of button presses) at which the individual stops to work for more alcohol. Also, the BrAC exposure measures will be determined. Alcohol craving in response to ghrelin will be measured using the Alcohol Visual Analogue Scale (A-VAS) and the Alcohol Urge Questionnaire (AUQ) during the PR sessions. Sensitivity to alcohol will be measured using the Drug Effects Questionnaire (DEQ), Biphasic Alcohol Effects Scale (BAES), and the Profile of Mood States (POMS), repeatedly during the PR sessions and the CASE Experience Questionnaire (CEQ) at the end of all sessions. fMRI BOLD signal in brain areas associated with incentive salience and areas associated with reward circuitry (including the ventral striatum) will be measured during the fMRI/alcohol clamp session. This study may facilitate the identification of a novel neuropharmacological target, thus facilitating the development of novel pharmacological treatments for alcoholism.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ASA/Ghrelin | Experimental | Drug: Ghrelin, Drug: AlcoholIntravenous 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. |
| ASA/Placebo | Placebo comparator | Drug: Placebo, Drug: AlcoholIntravenous 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 |
| fMRI/Ghrelin | Experimental | Drug: Ghrelin, Procedure: fMRIIntravenous 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. |
| fMRI/Placebo | Placebo comparator | Drug: Placebo, Procedure: fMRIIntravenous 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 |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (13 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ghrelin | Drug | ASA/Ghrelin, fMRI/Ghrelin |
| Placebo | Drug | ASA/Placebo, fMRI/Placebo |
| fMRI | Procedure or surgery | fMRI/Ghrelin, fMRI/Placebo |
| Alcohol | Drug | ASA/Ghrelin, ASA/Placebo |
Primary outcome
Alcohol Infusions Self-administered
Time frame: 120 minutes after the start of the infusion
The total number of alcohol infusions self-administered.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10604470Kojima 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.
- Background: PubMed 17407491Cummings 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.
- Background: PubMed 16759336Jerlhag 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.
- Background: PubMed 24775991Leggio 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.
- Background: PubMed 24090583Leggio 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.
- Background: PubMed 21392177Leggio 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.
- Background: PubMed 20440417Leggio 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.
- Results publication: PubMed 29133954Farokhnia 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.
- Derived from this study: PubMed 41329966Richardson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lorenzo Leggio, M.D. principal investigator
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ghrelin, fMRI and Alcohol in people with fMRI and Alcohol Drinking, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alcohol Infusions Self-administered (time frame: 120 minutes after the start of the infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01779024, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2018.