Effects of Ghrelin on Alcohol Cue Reactivity and Craving
Recruitment status was Recruiting
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 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|
- 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)].
- 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 frequency and intensity of 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 heart rate changes and salivation changes.
- Alcohol Attention Scale (AAS) [ 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 attention to the sight and smell of cues [as measured by the Alcohol Attention Scale (AAS)].
- Correlation between blood ghrelin levels and craving scores on the Alcohol-Visual Analogue Scale (A-VAS). [ Time Frame: given the blind design, this outcome will not be assessed immediately, but it will be assessed up to 1 year after the cue-reactivity experiment. ] [ Designated as safety issue: No ]Whether blood ghrelin levels are positively related to alcohol craving scores during the cue-reactivity (CR).
|Study Start Date:||April 2011|
|Estimated Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
|Active Comparator: Ghrelin (1 microg/kg)||
a single administration as a bolus of ghrelin 1 microg/kg
|Active Comparator: Ghrelin (3 microg/kg)||
a single administration as a bolus of ghrelin 3 microg/kg
|Placebo Comparator: Saline Solution||
Drug: Saline solution
a single administration as a bolus of saline solution (placebo)
|Contact: Lorenzo Leggio, M.D., M.Sc.||Lorenzo_Leggio@Brown.edu|
|United States, Rhode Island|
|Brown University Center for Alcohol and Addiction Studies||Recruiting|
|Providence, Rhode Island, United States, 02903|
|Contact: Lorenzo Leggio, M.D., M.Sc. Lorenzo_Leggio@Brown.edu|
|Principal Investigator: Lorenzo Leggio, M.D., Ph.D.|
|Sub-Investigator: George A. Kenna, Ph.D., R.Ph.|
|Sub-Investigator: Robert M Swift, M.D., Ph.D.|