Protocol Number: 08-AA-0125

Title:

Effect of Naltrexone on Craving and Ethanol-Induced Brain Activity

Number:

08-AA-0125

Summary:

This study will determine whether naltrexone, a medicine used to treat alcoholism, can lessen the craving for alcohol during alcohol withdrawal and examine how the drug affects brain activity during alcohol infusion.

People between 21 and 50 years of age who are right-handed, alcohol-dependent, and have at least one family member with a history of alcoholism, may be eligible for this study.

Participants are admitted to the NIH Clinical Center for 1 month for the following procedures:

Screening

-Medical history, alcohol-use history and family history of alcoholism

-Physical examination, psychological tests and blood tests

-Medicine to lessen alcohol withdrawal symptoms, if necessary

Days 1-7

-Alcohol detoxification

-Medical and psychological evaluations

-Assignment to naltrexone or placebo group

Days 7 through 28

-Drug treatment: Take naltrexone or placebo capsule every morning

-Additional alcohol-dependence treatment: Cognitive and behavioral therapies and participation in self-help groups, such as Alcoholics Anonymous

-Weekly questionnaires to measure mood and desire for alcohol

-Blood tests

-Alcohol craving stimulation test (day 7): Subjects handle and sniff water and then their favorite alcoholic beverage. They then rate their urge to drink alcohol and their level of anxiety and their heart rate is measured.

-Alcohol infusion test (day 9): Subjects have an MRI scan during infusion through a vein of saline (salt water), followed by infusion of alcohol. For this test, a catheter (plastic tube) is placed in a vein in each arm, one for administering the saline and then alcohol; the other for drawing blood samples to measure blood alcohol level and body chemistries. Before, during and after the infusion, subjects are asked to respond to questions about their feelings, cravings and mood changes.

Follow-up

Subjects are asked to participate in a 3-month outpatient assessment program involving five outpatient visits (at 1, 2, 4, 8 and 12 weeks after discharge). At each visit, they fill out questionnaires and to take a breathalyzer test and blood and urine tests for drugs. They may continue naltrexone therapy and weekly group therapy sessions during this time. Subjects who do not participate in the assessment program are contacted at home by phone once a week for 1 month and then every other week for the next 2 months to monitor alcohol abstinence.

Sponsoring Institute:

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

.INCLUSION CRITERIA:

All participants must:

-be right-handed

-between 21 and 50 years of age

-meet the DSM-IV diagnostic criteria for alcohol dependence (polysubstance abuse is common in younger alcohol-dependent patients, and will not be exclusionary)

-have a positive family history of alcoholism (one or more first-degree relatives with alcohol problems)

In addition, female participants:

-must have a negative urine pregnancy test (beta-hCG)

-of childbearing capability will be required to use a double contraceptive method (such as oral contraceptives, condom with spermicide or intra-uterine device with spermicide) from the start of the study until at least one month following the last dose of NTX.

EXCLUSION CRITERIA:

General exclusion criteria for the NIAAA Intramural treatment program:

-people who present with complicated medical problems requiring intensive medical or diagnostic management, such as uncontrolled hypertension, gastro-intestinal (GI) bleeding, major organ or body system dysfunction or thyroid disease

-people who are infected with 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 study procedures, such as psychotic illness, or severe dementia (individuals not competent to give informed consent)

-people who are unlikely or unable to complete the study because they 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

Specific exclusion criteria for this protocol include:

-clinically significant hepatobiliary disease

-a history of facial flushing in response to alcohol

-a history of seizures

-currently psychotic

-currently abusing opioids

-use of psychotropic medications (antidepressant, lithium, antipsychotic, anxiolytic, antiepileptic) regularly within the last 4 weeks prior to admission

-having a positive pregnancy test, contemplating pregnancy in the next 3 months, nursing, or not using an effective contraceptive method (if the participant is of child-bearing potential)

-a history of allergy or unusual reactions to NTX

-have received treatment with NTX in the six-month period prior to enrollment

-presence of ferromagnetic brain aneurysm clips, implanted pacemaker, hearing aid, or any other metallic implant, such as pins, screws, plates, dentures, or non-removable jewelry, in or on the body

-pronounced claustrophobia

Special Instructions:

Currently Not Provided

Keywords:

Alcohol

Naltrexone

fMRI

Alcoholism

Alcoholics

Recruitment Keyword(s):

Alcohol Dependence

Alcoholism

Condition(s):

Alcohol Dependence

Alcoholism

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Naltrexone

Supporting Site:

National Institute on Alcohol Abuse and Alcoholism

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Appel SB, Wise L, McDaid J, Koyama S, McElvain MA, Brodie MS. The effects of long chain-length n-alcohols on the firing frequency of dopaminergic neurons of the ventral tegmental area. J Pharmacol Exp Ther. 2006 Sep;318(3):1137-45. Epub 2006 Jun 1.

Barr CS, Schwandt M, Lindell SG, Chen SA, Goldman D, Suomi SJ, Higley JD, Heilig M. Association of a functional polymorphism in the mu-opioid receptor gene with alcohol response and consumption in male rhesus macaques. Arch Gen Psychiatry. 2007 Mar;64(3):369-76.

Bart G, Kreek MJ, Ott J, LaForge KS, Proudnikov D, Pollak L, Heilig M. Increased attributable risk related to a functional mu-opioid receptor gene polymorphism in association with alcohol dependence in central Sweden. Neuropsychopharmacology. 2005 Feb;30(2):417-22.

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