Effect of Naltrexone on Craving and Ethanol-Induced Brain Activity
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 试验地点
- 2
- 主要终点
- BOLD response during the ethanol infusion challenge
研究概览
简要总结
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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详细描述
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.
Objectives:
To study the effect of NTX on the blood oxygen level dependent (BOLD) response in the ventral striatum area of the brain in response to an ethanol infusion.
To study the effect of NTX on cue reactivity (CR) to alcohol-associated cues.
Study population:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 21 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
结局指标
主要结局
BOLD response during the ethanol infusion challenge
次要结局
- Self-reported AUQ, PACS, OCDS, POMS and cue-induced craving during the CR session