Effects of Ghrelin on Alcohol Administration in Non-Treatment Seeking Heavy Drinkers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Alcohol Infusions Self-administered
研究概览
简要总结
Background:
- Ghrelin is a hormone in the human body that is mostly produced by the stomach. It makes people feel hungry, and also is connected with the desire to drink alcohol. Researchers want to test ghrelin to see if it can be used to control alcohol cravings and use. They will compare doses of ghrelin with a placebo in people who drink heavily.
Objectives:
- To study the effects of ghrelin on alcohol craving and use.
Eligibility:
- Individuals between 21 and 60 years of age who are heavy drinkers but are not seeking treatment for alcohol use.
- Participants must on average have more than 20 drinks per week for men, and more than 15 drinks per week for women.
Design:
- Participants will have a screening visit, four 2-night study visits, and a follow-up visit.
- Participants will be screened with a physical exam and medical history. They will provide urine and breath samples for drug testing. They will also answer questions about mood and physical symptoms, and about alcohol and other cravings.
- At the study visits, participants will stay overnight at the National Institutes of Health clinical center. They will spend the night at the center, have tests on the next day, and go home on the following morning. At each visit, participants will receive a ghrelin or placebo infusion, and will complete a series of tasks.
- For the first and second study visits, participants will have tests of alcohol craving and use. They will be able to receive alcohol infusions through a computer program that tests response time and craving reactions. At the same time, they will have a ghrelin or a placebo infusion. Blood alcohol levels, reaction time, and craving will be studied.
- For the third and fourth study visits, participants will have a magnetic resonance imaging (MRI) study. They will have an initial MRI to provide a picture of the brain. They will then have a functional MRI during which they will respond to a computer test. The test will allow them to win points for snack food or alcohol. This test will look at the brain s response time and craving reactions.
- There will be a follow-up visit 1 week after the fourth study visit. Some of the tests from the screening visit will be repeated.
详细描述
Objective:
Ghrelin is a 28-amino acid peptide acting as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus (ARC), a region that controls the intake of food and other substances, including alcohol. In addition to the ARC, GHS receptors (GHS-Rs) are also highly expressed in the caudal brain stem, the ventral tegmental area (VTA), hippocampus, substantia nigra, and dorsal and medial raphe nuclei. The expression of the GHS-R in the mesolimbic dopamine (DA) pathway suggests that ghrelin could play a role in reward processing. The role of ghrelin in the DA reward processing and the role of the DA reward system in alcoholism suggest a role of ghrelin in alcoholism. Consistent with this hypothesis, preclinical studies demonstrate that both ghrelin and ethanol activate the cholinergic-dopaminergic reward link, implying neurochemical analogies between ghrelin and ethanol. This supports the hypothesis that ghrelin is involved in mediating the rewarding properties of ethanol. Additional animal experiments demonstrate that the central ghrelin action not only stimulates the reward processing but is also required for stimulation of that system by alcohol. Human studies show reduced ghrelin levels in actively drinking alcoholics; increased ghrelin levels during alcohol abstinence; and a positive correlation between ghrelin level and alcohol craving scores. More recently, a study conducted at Brown University by the PI demonstrated the safety of the administration IV of human ghrelin to non-treatment seeking alcohol-dependent heavy drinking individuals. Furthermore, a preliminary interim analysis shows that IV ghrelin administration may lead to a temporary significant increase in alcohol craving. The primary objective of this protocol is to investigate whether IV ghrelin, as compared to placebo, will increase motivation for alcohol reward, as measured by a progressive ratio (PR) schedule paradigm with IV alcohol self-infusion (primary aim). We will also assess a number of secondary aims. Specifically, we will also assess whether IV ghrelin, as compared to placebo, will also alter urges to drink and the subjective response to IV alcohol. Adverse events will also be assessed to ensure the safety of the IV coadministration of ghrelin and alcohol. During an fMRI/alcohol clamp session, fMRI will be used to see whether ghrelin affects the activation of the ventral striatum induced by acute IV alcohol administration and the incentive salience of cues associated with alcohol administration.
Study Population:
Male and female participants will be non-treatment seeking heavy drinking volunteers.
Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ASA/Ghrelin
Intravenous acyl-ghrelin [a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)] was administered on the first ASA visit; Intravenous placebo [packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor] was administered on the second ASA visit.
干预措施: Alcohol (Drug)
ASA/Ghrelin
Intravenous acyl-ghrelin [a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)] was administered on the first ASA visit; Intravenous placebo [packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor] was administered on the second ASA visit.
干预措施: Ghrelin (Drug)
ASA/Placebo
Intravenous placebo [packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor] was administered on the first ASA visit; Intravenous acyl-ghrelin [a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)] was administered on the second ASA visit
干预措施: Placebo (Drug)
ASA/Placebo
Intravenous placebo [packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor] was administered on the first ASA visit; Intravenous acyl-ghrelin [a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)] was administered on the second ASA visit
干预措施: Alcohol (Drug)
fMRI/Ghrelin
Intravenous acyl-ghrelin [a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)] was administered on the first fMRI visit; Intravenous placebo [packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor] was administered on the second fMRI visit.
干预措施: Ghrelin (Drug)
fMRI/Ghrelin
Intravenous acyl-ghrelin [a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)] was administered on the first fMRI visit; Intravenous placebo [packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor] was administered on the second fMRI visit.
干预措施: fMRI (Procedure)
fMRI/Placebo
Intravenous placebo [packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor] was administered on the first fMRI visit; Intravenous acyl-ghrelin [a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)] was administered on the second fMRI visit
干预措施: Placebo (Drug)
fMRI/Placebo
Intravenous placebo [packed in Dextrose 5% / Water USP 50mL bags and made identical to ghrelin in terms of appearance, texture, and odor] was administered on the first fMRI visit; Intravenous acyl-ghrelin [a loading dose (3 mcg/kg), followed by a continous infusion (16.9 ng/kg/min)] was administered on the second fMRI visit
干预措施: fMRI (Procedure)
结局指标
主要结局
Alcohol Infusions Self-administered
时间窗: 120 minutes after the start of the infusion
The total number of alcohol infusions self-administered.
次要结局
未报告次要终点