The Effect of Naltrexone on Alcohol Craving and on Brain Activity During Alcohol Infusion

NCT00667771 | Completed Early Phase 1

• 2 other identifiers: 08012508-AA-0125
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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. ...

Conditions

Alcohol Dependence; Alcoholism

Keywords

Alcohol; Naltrexone; fMRI; Alcoholism; Alcoholics; Alcohol Dependence

Outcome Measures

Primary Outcomes (1)

• BOLD response during the ethanol infusion challenge

Secondary Outcomes (1)

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

Interventions

Naltrexone DRUG

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• All participants must:
• be right-handed
• between 21 and 50 years of age
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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. doi: 10.1124/jpet.106.105148. Epub 2006 Jun 1.

  PMID: 16740620 BACKGROUND

• 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. doi: 10.1001/archpsyc.64.3.369.

  PMID: 17339526 BACKGROUND

• 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. doi: 10.1038/sj.npp.1300598.

  PMID: 15525999 BACKGROUND

• Spagnolo PA, Ramchandani VA, Schwandt ML, Zhang L, Blaine SK, Usala JM, Diamond KA, Phillips MJ, George DT, Momenan R, Heilig M. Effects of naltrexone on neural and subjective response to alcohol in treatment-seeking alcohol-dependent patients. Alcohol Clin Exp Res. 2014 Dec;38(12):3024-32. doi: 10.1111/acer.12581.

  PMID: 25581657 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: April 25, 2008
• First Posted: April 28, 2008
• Study Start: April 22, 2008
• Primary Completion: December 27, 2010
• Study Completion: April 4, 2011
• Last Updated: July 2, 2017

Record last verified: 2011-04-04

Locations

US (1)