Effects of Ghrelin on Alcohol Cue Reactivity and Craving

April 30, 2014 updated by: Lorenzo Leggio, Brown University

Only a few medications are approved for the treatment of alcohol dependence and there exists a substantial need for discovering ways to provide more effective treatments. Accordingly, identifying new potential neuropharmacological targets in the treatment of alcohol dependence represents a high priority in public health. Ghrelin is a 28-amino acid peptide acting as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Ghrelin was first isolated from the stomach, but a central hypothalamic production of ghrelin has also been demonstrated. Ghrelin plays a key role in the regulation of appetite. Consistent with the common neurobiological substrates for control of food and alcohol consumption, preclinical investigations suggest that ghrelin plays a role in the neurobiology of alcohol dependence, thus representing a new potential neuropharmacology target. In keeping with the preclinical studies, human investigations showed that alcohol consumption affects blood ghrelin levels and that blood ghrelin levels significantly and positively correlate with craving measurements in alcohol-dependent individuals. The effects of exogenous ghrelin injected intravenous (i.v.) in alcohol-dependent individuals, however, have never been investigated. The current project proposes a randomized double-blind placebo-controlled 3-group between-subject laboratory study aimed at investigating the effects of exogenous ghrelin i.v. on non-treatment seeking alcohol-dependent subjects in terms of urges to drink, attention to cues and related psychophysiological measures. This project has the goals to: i) conduct an alcohol laboratory study testing the role of ghrelin i.v., therefore demonstrating the feasibility of such a study and the safety of ghrelin i.v. when administered to alcohol-dependent individuals; and ii) explore the effects of ghrelin i.v. on alcohol craving assessed under controlled conditions, such as a cue-reactivity (CR) experiment.

This study will address whether alcohol craving is affected when ghrelin levels are modified acutely via a ghrelin i.v. injection. Given the crucial need to expand our understanding of the underlying neurobiology of alcoholism, this study potentially will lead to identify new targets for the development of pharmacological treatments that may improve interventions for alcohol dependent individuals.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Brown University Center for Alcohol and Addiction Studies

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Understanding that this is not a treatment study.
  • Breath alcohol concentration (BAC) equal to 0.00 when the participants sign the informed consent document.
  • Age between 18 and 70 years old (inclusive).
  • Female participants must be postmenopausal for at least one year, surgically sterile, or practicing an effective method of birth control before entry and throughout the study; have a negative urine pregnancy test at screening and cue-reactivity (CR) visits.
  • Diagnosis of Alcohol dependence using Module E of the structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders - Text Revised (DSM-IV-TR).
  • Participants must meet criteria for heavy drinking, defined as averaging ≥4 drinks/day for women and ≥5 drinks/day for men during a consecutive 30-day period within the 90 days prior to baseline evaluation
  • Good health as confirmed by medical history, physical examination, electrocardiogram (ECG), laboratory tests and vital signs.
  • Participant must be willing to receive an I.V. line.

Exclusion Criteria:

  • Individuals expressing interest in treatment for alcoholism.
  • Females who are of child bearing potential and not practicing effective birth control.
  • Current (last 12 months) diagnosis of dependence on any psychoactive substance other than alcohol and nicotine (according to the DSM-IV-TR)
  • DSM-IV-TR Axis I criteria for a lifetime diagnosis of schizophrenia, bipolar disorder, or other psychoses; an active illness within the past 6 months that meet the DSM-IV-TR criteria for a diagnosis of Major Depressive Disorder or Anxiety Disorder; in the investigators' opinion, moderate to severe risk of suicide (e.g. active plan, or attempt in last 6 months).
  • History of hospitalization for alcohol intoxication delirium, alcohol withdrawal delirium or seizure.
  • Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) ≥ 10, at any assessment.
  • Positive urine drug screen at baseline for any illegal substance other than marijuana (a urine drug screen may be repeated once during the screening period).
  • Subjects who have received any behavioral and/or pharmacological treatment for alcoholism within the past 30 days.
  • Current use of psychotropic medications that cannot be discontinued.
  • Clinically significant medical abnormalities [e.g., alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >300% the upper limit of normal].
  • Significant medical conditions, such as cancer, liver cirrhosis, heart chronic failure, chronic kidney failure, chronic intestinal diseases (e.g., Crohn's disease), chronic neurological disorders (e.g., tardive dyskinesia, epilepsy, Parkinson's disease), diabetes, obesity [Body Mass Index(BMI) ≥ 30 kg/m2].
  • Participants with a history of hypotension clinically significant (e.g.: history of fainting and/or syncopal attacks).
  • No history of adverse reactions or hypersensitivity to ghrelin i.v. nor history of adverse reactions to needle puncture.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ghrelin (1 microg/kg)
A 1 microg/kg dose of intravenous human acetylated ghrelin was administered once approximately 10 minutes before the start of the alcohol cue-reactivity experiment.
Drug: Ghrelin
A 1 microg/kg dose of intravenous human acetylated ghrelin was administered once approximately 10 minutes before the start of the alcohol cue-reactivity experiment.
Other Names:
  • human acetylated ghrelin
Drug: Ghrelin
A 3 microg/kg dose of intravenous human acetylated ghrelin was administered once approximately 10 minutes before the start of the alcohol cue-reactivity experiment.
Other Names:
  • human acetylated ghrelin
Active Comparator: Ghrelin (3 microg/kg)
A 3 microg/kg dose of intravenous human acetylated ghrelin was administered once approximately 10 minutes before the start of the alcohol cue-reactivity experiment.
Drug: Ghrelin
A 1 microg/kg dose of intravenous human acetylated ghrelin was administered once approximately 10 minutes before the start of the alcohol cue-reactivity experiment.
Other Names:
  • human acetylated ghrelin
Drug: Ghrelin
A 3 microg/kg dose of intravenous human acetylated ghrelin was administered once approximately 10 minutes before the start of the alcohol cue-reactivity experiment.
Other Names:
  • human acetylated ghrelin
Placebo Comparator: Saline Solution
Intravenous saline solution (matched placebo) was administered once approximately 10 minutes before the start of the alcohol cue-reactivity experiment.
Drug: Saline solution
Intravenous saline solution (matched placebo) was administered once approximately 10 minutes before the start of the alcohol cue-reactivity experiment.
Other Names:
  • matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Alcohol Visual Analogue Scale (A-VAS)
Time Frame: approximately 30 minutes after drug administration

Whether ghrelin intravenous (i.v.), as compared to saline i.v., dose-dependently results in increased cue-reactivity (CR) responses to alcohol cues in terms of urge to drink [as measured by the Alcohol Visual Analogue Scale (A-VAS)].

The A-VAS was rated on 11-point anchored Likert-type scales, where 0 is the minimum score (no craving) and 11 is the maximum score (highest craving intensity). The change in the A-VAS score (deltaA-VAS) was used to indicate decrease (-d) or increase (+d) in craving intensity.
approximately 30 minutes after drug administration
Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability.
Time Frame: participants will be followed after the cue-reactivity experiment, an expected average of 7 days
Whether ghrelin intravenous (i.v.), as compared to saline i.v., does not significantly increase Adverse Events (AEs).
participants will be followed after the cue-reactivity experiment, an expected average of 7 days
Salivation
Time Frame: approximately 30 minutes after drug administration
Whether ghrelin intravenous (i.v.), as compared to saline i.v., dose-dependently results in increased cue-reactivity (CR) responses to alcohol cues in terms of psychophysiological responses, namely salivation changes.
approximately 30 minutes after drug administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brown University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2011

Primary Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

August 26, 2010

First Submitted That Met QC Criteria

August 26, 2010

First Posted (Estimate)

August 27, 2010

Study Record Updates

Last Update Posted (Estimate)

May 15, 2014

Last Update Submitted That Met QC Criteria

April 30, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1005000183

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Alcoholism

Clinical Trials on Ghrelin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Türkiye

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe