A Novel Compound for Alcoholism Treatment
|ClinicalTrials.gov Identifier: NCT02039349|
Recruitment Status : Completed
First Posted : January 17, 2014
Last Update Posted : March 15, 2018
- Hormones are naturally occurring chemicals in your body. Ghrelin is a hormone that is mainly produced by the stomach and stimulates appetite. Some studies suggest it may stimulate alcohol craving and use. Drugs have been developed that block ghrelin. Researchers want to know if people can tolerate a particular drug that blocks ghrelin. It will be given at two dose levels, combined with alcohol.
- To determine if a drug that may decrease alcohol consumption when given along with alcohol is safe and tolerable.
- Healthy adults 21-65 years old who have 14 (women) to 21 (men) drinks a week.
- No one of childbearing potential can participate.
- Participants will have 3 inpatient clinic visits; each will last 4 days.
- They will have physical exam and blood and urine tests.
- They will have breath tests for alcohol and smoking.
- They will answer health and mood questions.
- Researchers will measure their reaction to smelling alcohol and tasting a sweet drink.
- They will eat only the food provided by the clinic. They will keep a food diary 1 day before each stay.
- They will be randomly assigned to take the study drug or placebo 5 times each stay.
- On Day 3, they will drink alcohol after taking the drug. They will give many blood samples that day through a tube inserted in their skin.
- Smokers can take smoke breaks. Once, they will smoke a cigarette through a device.
- One week after the last stay, participants will have a follow-up visit to answer questions.
|Condition or disease||Intervention/treatment||Phase|
|Alcoholism Alcohol-Related Disorders Alcohol Dependence Alcohol Drinking Related Problems Alcohol Drinking||Drug: PF-05190457||Phase 1|
Objective: Ghrelin is a 28-aminoacid peptide that stimulates appetite and food intake. It is an endogenous ligand for the growth hormone secretagogue receptor (GHSR1a). Preclinical studies suggest that ghrelin modulates alcohol reward processing. Furthermore, findings from a translational human lab study at Brown University (PI: Leggio) indicate that intravenous (IV) ghrelin administration, compared to placebo, results in an acute increase in craving for alcohol during a cue-reactivity experiment in alcoholic individuals. Therefore, an orally bioavailable, ghrelin receptor antagonist, that can pass through the blood brain barrier holds particular promise as an AD treatment. This project has been recently funded by NCATS. The goals of this protocol are to generate preliminary evidence on the safety and efficacy of a ghrelin receptor antagonist (GHSR1a antagonist), PF-05190457, an existing molecule available under the NIH-Industry Pilot Program at NCATS.
Study population: Non-treatment seeking heavy drinkers (n =20). The study will be conducted in the Inpatient Unit at the NIAAA Intramural Clinical Program.
Study Design: Single-blind dose-escalating placebo-controlled inpatient study using PF-05190457, in non-treatment seeking heavy drinking subjects. This Phase 1b study will be a within-subject design.
Outcome measures: Primary objectives will be to determine: 1) the number of adverse events (AEs) experienced, compared between all three PF-05190457 dose categories (0mg or placebo, 50mg, and 100mg b.i.d.); and 2) the total concentration of the drug, compared between the two non-placebo drug doses (50mg and 100mg b.i.d.), when co-administered with alcohol. We hypothesize that both doses of PF-05190457, as compared to placebo, will not result in an increased number of AEs. As a secondary objective, we will determine whether PF-05190457 dose-dependently affects the subjective effects of alcohol and craving. We will include pharmacokinetics (PK) and pharmacodynamic (PD) investigations conducted at University of Rhode Island (URI; Associate Investigator: Akhlaghi). The PK/PD component will include (i) measuring total, unbound or tissue concentrations of the drug using liquid chromatography tandem mass spectrometry (LC-MS/MS) and evaluation of biomarkers of effect and (ii) estimation of PK and PD parameters by the use of conventional and semi-mechanistic modeling approaches to assist in identifying an optimal dosing regimen of the drug in AD.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Crossover Assignment|
|Official Title:||A Novel Compound for Alcoholism Treatment: A Translational Strategy|
|Study Start Date :||January 3, 2014|
|Primary Completion Date :||October 1, 2015|
|Study Completion Date :||December 24, 2017|
- Side effects/adverse events and maximum tolerated dose of PF-05190457 alone and in combination with alcohol administration. [ Time Frame: 3 days ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02039349
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Lorenzo Leggio, M.D.||National Institute on Alcohol Abuse and Alcoholism (NIAAA)|