Effect of LY686017 on Alcohol Craving

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00310427
First received: April 1, 2006
Last updated: April 13, 2010
Last verified: April 2010
  Purpose

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 After having been withdrawn from alcohol for at least 2 days, participants receive either 50 mg of LY686017 or placebo (an inactive substance that looks like the study drug) every morning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.

Condition Intervention Phase
Alcohol Dependence
Alcoholism
Drug: LY686017
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: NK1 Receptor Antagonism for Treatment of Anxiety and Craving in Anxious Alcohol Dependent Subjects During Early Abstinence

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Craving for Alcohol (Spontaneous) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). This is a self-report rating scale, with scores ranging from 8 (lowest craving value) to 56 (highest craving value).

  • Change From Baseline in Spontaneous Alcohol Craving at Week 1, During the First of Two Weekly Ratings. [ Time Frame: Week 1/Rating 1 minus baseline ] [ Designated as safety issue: No ]
    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). This is a self-report rating scale, with scores ranging from 8 (lowest craving value) to 56 (highest craving value).

  • Change From Baseline in Spontaneous Alcohol Craving at Week 1, During the Second of Two Weekly Ratings. [ Time Frame: Week 1 Rating 2 minus baseline ] [ Designated as safety issue: No ]
    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). This is a self-report rating scale, with scores ranging from 8 (lowest craving value) to 56 (highest craving value).

  • Change From Baseline in Spontaneous Alcohol Craving at Week 2, During the First of Two Weekly Ratings. [ Time Frame: Week 2 Rating 1 minus baseline ] [ Designated as safety issue: No ]
    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). This is a self-report rating scale, with scores ranging from 8 (lowest craving value) to 56 (highest craving value).

  • Change From Baseline in Spontaneous Alcohol Craving at Week 2, During the Second of Two Weekly Ratings. [ Time Frame: Week 2 Rating 2 minus baseline ] [ Designated as safety issue: No ]
    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). This is a self-report rating scale, with scores ranging from 8 (lowest craving value) to 56 (highest craving value).

  • Change From Baseline in Spontaneous Alcohol Craving at Week 3, During the First of Two Weekly Ratings. [ Time Frame: Week 3 Rating 1 minus baseline ] [ Designated as safety issue: No ]
    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). This is a self-report rating scale, with scores ranging from 8 (lowest craving value) to 56 (highest craving value).

  • Change From Baseline in Spontaneous Alcohol Craving at Week 3, During the Second of Two Weekly Ratings. [ Time Frame: Week 3 Rating 2 minus baseline ] [ Designated as safety issue: No ]
    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). This is a self-report rating scale, with scores ranging from 8 (lowest craving value) to 56 (highest craving value).

  • Craving for Alcohol Evoked by Alcohol-cue Challenge [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). This is a self-report rating scale, with scores ranging from 8 (lowest craving value) to 56 (highest craving value).


Enrollment: 66
Study Start Date: March 2006
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY686017
Subjects received 50 mg of the NK1 antagonist LY686017 orally on a daily basis.
Drug: LY686017
50 mg administered orally on a daily basis
Placebo Comparator: Placebo
Subjects received placebo orally on a daily basis
Drug: Placebo
Administered on a daily basis

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Age 21 - 65.
  • DSM-IV diagnosis of alcohol dependence on SCID, alcohol problems as primary complaint among substance use disorder, and alcohol use within the last month.
  • Spielberger trait anxiety score greater than 39.
  • Females of childbearing potential must agree to use a reliable method of birth control during the study. Reliable methods of birth control include oral contraceptives or Norplant(Registered Trademark); barrier methods such as diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, or intrauterine devices; a partner with a vasectomy; or abstinence from intercourse.

EXCLUSION CRITERIA:

Subjects will be excluded if they meet any of the criteria below. The criteria for enrollment will be followed explicitly. If a subject who does not meet enrollment criteria is inadvertently enrolled, that subject will be discontinued from the study and Eli Lilly will be contacted.

General exclusion criteria for the NIAAA intramural treatment program:

  • People who present with complicated medical problems requiring intensive medical or diagnostic management, such as hypertensive emergency, serious GI bleeding, major organ or body system dysfunction such as decompensated liver disease, renal failure, myocardial ischemia, congestive heart failure or cerebrovascular disease, major endocrine problems such as uncontrolled diabetes, pancreatic or thyroid disease.
  • People who are infected with the Human Immunodeficiency Virus (HIV).
  • Serious neuro-psychiatric conditions which impair judgment or cognitive function to an extent that precludes them from providing informed consent or complying with treatment, such as psychotic illness or severe dementia (incompetent individuals).
  • People who are unlikely or unable to complete the treatment program because they become or are likely to be incarcerated while on the protocol.
  • People who are required to receive treatment by a court of law or who are involuntarily committed to treatment.
  • People with uncontrolled hypertension

Study specific exclusion criteria:

  • People who are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
  • People who are employees of Eli Lilly & Co.
  • Treatment within the last 30 days with a drug [not including study drug] that has not received regulatory approval for any indication at the time of study entry.
  • A history of seizures, other than documented febrile seizures
  • Patients with clinically significant hepatobiliary disease (as evaluated by a trained hepatologist) will be excluded from the protocol
  • Pregnancy or lactation (negative pregnancy test required)
  • Regular use of psychotropic medication (antidepressant, lithium, antipsychotic, anxiolytic, antiepileptic) within last 4 weeks, with the exception of benzodiazepines administered within the NIAAA program as part of alcohol withdrawal treatment.
  • Inability or unwillingness to participate in an fMRI scan, including presence of metallic objects in the body, or pronounced claustrophobia
  • Hypopituitarism or reduced adrenal secretory activity because of the risk of precipitating acute adrenal failure with metyrapone.
  • Porphyria because metyrapone may be porphyrinogenic based on data from in-vitro systems.
  • Thyroid dysfunction, which may alter the response to metyrapone.
  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: NCT00310427

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Eli Lilly and Company
  More Information

Additional Information:
Publications:
Responsible Party: Markus A. Heilig, M.D./National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00310427     History of Changes
Obsolete Identifiers: NCT00401037
Other Study ID Numbers: 060129, 06-AA-0129
Study First Received: April 1, 2006
Results First Received: March 5, 2010
Last Updated: April 13, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Anxiety
Alcohol Dependence
Alcoholism

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 11, 2014