The Effect of Naltrexone on Alcohol Craving and on Brain Activity During Alcohol Infusion - Full Text View

Sponsored by:	National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00667771

Purpose

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.

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Condition	Intervention	Phase
Alcohol Dependence Alcoholism	Drug: Naltrexone	Phase 0

MedlinePlus related topics: Alcoholism

Drug Information available for: Ethanol Naltrexone Naltrexone hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Effect of Naltrexone on Craving and Ethanol-Induced Brain Activity

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

Primary Outcome Measures:

BOLD response during the ethanol infusion challenge

Secondary Outcome Measures:

Self-reported AUQ, PACS, OCDS, POMS and cue-induced craving during the CR session

Estimated Enrollment:	70
Study Start Date:	April 2008

Intervention Details:

N/A

Detailed Description:

Alcoholism is a chronic, progressive, brain disorder with a profound impact on individuals' lives and economic cost to society. The positive reinforcing effect of alcohol is a key element in the transitional development from alcohol intake to alcohol addiction. Findings from animal and human studies indicate that the rewarding properties of ethanol arise in part from a complex interaction between alcohol, endogenous opioids, and dopamine (DA) systems. Acute administration of ethanol increases the release of opioid peptides, which in turn, increases the release of DA in the mesocorticolimbic system. Naltrexone (NTX), an opioid receptor antagonist, has been studied widely in both preclinical and clinical research for the treatment of alcoholism. Numerous clinical studies have shown that short-term use of NTX on alcohol-dependent patients effectively prevents relapse and reduces the level of craving. Genetic studies have suggested that individuals with mu-opioid receptors (OPRMs) encoded by the 118G gain-of function variant allele experience a greater therapeutic response to NTX. There are no data utilizing functional Magnetic Resonance Imaging (fMRI) to study the effect of NTX on brain activity during an intravenous (IV) infusion of ethanol.

Eligibility

Ages Eligible for Study:	21 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667771

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

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.

Study ID Numbers:	080125, 08-AA-0125
Study First Received:	April 25, 2008
Last Updated:	March 31, 2009
ClinicalTrials.gov Identifier:	NCT00667771 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Alcohol
Naltrexone
fMRI
Alcoholism

Alcoholics
Alcohol Dependence
Alcoholism

Study placed in the following topic categories:

Mental Disorders
Narcotic Antagonists
Naltrexone
Alcoholism
Substance-Related Disorders

Disorders of Environmental Origin
Narcotics
Alcohol-Related Disorders
Peripheral Nervous System Agents
Ethanol

Additional relevant MeSH terms:

Narcotic Antagonists
Physiological Effects of Drugs
Disorders of Environmental Origin
Pharmacologic Actions
Mental Disorders
Sensory System Agents
Therapeutic Uses

Alcoholism
Naltrexone
Substance-Related Disorders
Alcohol-Related Disorders
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 07, 2009