This study will determine whether the experimental drug LY686017 can reduce a person's desire
for alcohol. A brain chemical called Substance P acts at places in the brain called NK1
receptors. Substance P is released in response to stress and gives rise to behaviors that are
thought to represent anxiety. LY686017 blocks Substance P from acting at the NK1 receptors.
People between 21 and 65 years of age who have been drinking on a regular basis for at least
one month before entering the study, who meet the criteria for alcohol dependence and who
have an elevated score on a general test of anxiety may be eligible for this study.
Participants are admitted to the NIH Clinical Center for 35 days. They participate in an
alcohol treatment program in addition to the research study. After having been withdrawn from
alcohol for at least 2 days, participants receive either 50 mg of LY686017 or placebo (an
inactive substance that looks like the study drug) every morning for 28 days. In addition to
drug treatment, they undergo the following procedures:
- Functional magnetic resonance imaging (fMRI): In the last week of the study, subjects
undergo MRI to study the amount of blood going to brain structures thought to be
involved in anxiety and craving. During the procedure, they look at pictures of faces
exhibiting various emotions and pictures related to alcohol.
- Cue reactivity: At the beginning and towards the end of the study, subjects are asked to
rate their alcohol craving and their anxiety level while they sniff and handle their
favorite alcoholic beverage or water.
- Metyrapone test: During weeks 1 and 4 of the study, subjects are given metyrapone - a
drug that interferes with the body's ability to make the stress hormone cortisol - to
determine how LY686017 affects the body's hormonal response. The drop in cortisol from
metyrapone administration causes the brain to release ACTH, a hormone that causes the
adrenal gland to make cortisol.
- Trier test: In the last week of the study, subjects give a 5-minute speech to three
people and are then asked to subtract numbers in their head. Then they are asked to rate
their feelings and desire for alcohol on two rating scales. Blood is drawn from a saline
lock at the beginning and end of the test to measure hormone levels.
- Rating scales: Subjects complete an Obsessive Drinking Scale weekly and an Alcohol Urge
Questionnaire and Comprehensive Psychiatric Rating Scale twice a week.
- Blood tests: Blood samples are collected periodically to check blood chemistries,
clotting time, and the amount of LY686017 in the blood.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)