Effects of Ghrelin on Alcohol Cue Reactivity and Craving

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lorenzo Leggio, Brown University
ClinicalTrials.gov Identifier:
NCT01190085
First received: August 26, 2010
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Alcoholism
Drug: Ghrelin
Drug: Saline solution

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Effects of Ghrelin on Alcohol Cue Reactivity and Craving

Resource links provided by NLM:


Further study details as provided by Brown University:

Primary Outcome Measures:
  • Alcohol Visual Analogue Scale (A-VAS) [ Time Frame: approximately 30 minutes after drug administration ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: Yes ]
    Whether ghrelin intravenous (i.v.), as compared to saline i.v., does not significantly increase Adverse Events (AEs).

  • Salivation [ Time Frame: approximately 30 minutes after drug administration ] [ Designated as safety issue: No ]
    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.


Enrollment: 45
Study Start Date: April 2011
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 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 Name: 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 Name: matched placebo

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01190085

Locations
United States, Rhode Island
Brown University Center for Alcohol and Addiction Studies
Providence, Rhode Island, United States, 02903
Sponsors and Collaborators
Brown University
  More Information

Publications:

Responsible Party: Lorenzo Leggio, Principal Investigator, Brown University
ClinicalTrials.gov Identifier: NCT01190085     History of Changes
Other Study ID Numbers: 1005000183
Study First Received: August 26, 2010
Results First Received: December 1, 2013
Last Updated: April 30, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Brown University:
alcoholism
ghrelin
craving

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Pharmaceutical Solutions
Ethanol
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014