OPRM1 A118G SNP Effect on Striatal Dopamine Response to an IV Opiate
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- 11C Raclopride Binding Potential in Nucleus Accumbens
研究概览
简要总结
Background:
- Small differences in genes may alter responses to drugs. One gene that has different forms is the mu opioid receptor gene. People with one form of this gene are more sensitive to alcohol. People with a different form are sometimes more sensitive to pain. Morphine and other prescription pain pills produce pain relief by acting at the mu opioid receptor. Researchers want to see the effect of morphine on brain reward and subjective effects. Morphine is a strong but short-acting pain medication that is sometimes used for anesthesia during surgery.
Objectives:
- To compare the effect of morphine on brain measures of dopamine release using imaging.
Eligibility:
- Individuals between 21 and 55 years of age who have previously taken pain pills prescribed to treat pain from a medical or dental procedure.
Design:
- This study has a screening phase and a study phase. The screening phase involves one or two visits of 5 to 6 hours. The study phase consists of 4 study visits. Each study visit will take about 8 hours.
- Participants will be screened with a medical and psychiatric history and physical exam. They will be asked about drinking and drug-taking history, and any family history of alcoholism or drug abuse. Blood, urine, and breath samples will be collected.
- During the first study visit, an MRI scan may be performed, questionnaires completed, and a blood sample collected for genetic testing.
- During study visit 2, participants will test their pain sensitivity by placing one hand in cold water. Pupil diameter will be measured after the sensitivity test. After a blood sample is taken, participants will receive the morphine or a salt solution. The sensitivity test and pupil diameter test will be repeated. Final blood samples will be collected. A brief physical exam will also be performed.
- During study visits 3 and 4, participants will receive morphine or a salt solution during a PET scan. Questionnaires to assess subjective effects will be administered. Final blood samples will be collected. A brief physical exam will also be performed.
- Participants will stay in the clinic until the effects of the drug have worn off after study visits 2, 3, and 4.
- About 1 week after the study session, participants will have a follow-up phone call.
详细描述
Objectives
Mesolimbic dopamine (DA) release is a key signal for drug reward, and endogenous opioids are thought to exert their effects in part by modulating the activity of this system. A functional µ-opioid receptor (OPRM1) A118G single nucleotide polymorphism (SNP) has been associated with increased risk for heroin addiction in some studies. This polymorphism has been shown to confer differential pain sensitivity and to alter the release of DA following an alcohol challenge. The objective of this study is to examine the role of the A118G OPRM1 polymorphism for responses to a challenge of an opiate (morphine) with regard to psycho-physiological variables measured in the laboratory and for brain dopamine release measured by [11C]raclopride PET.
Study Population
Healthy male participants who have had experience with oral prescription analgesics (e.g., Oxycontin, Vicodin, Percocet, oxycodone) will be recruited for the study. These volunteers will be screened to obtain samples of two groups of subjects: 1) persons homozygous for the major 118A allele (118AA genotype); 2) persons carrying one or two copies of the variant 118G allele (118AG or 118GG genotype, hereafter called 118GX). We will recruit up to 120 participants to obtain 40 completers per genotype for the study.
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
- Double (Participant, Investigator)
盲法说明
Bliniding
入排标准
- 年龄范围
- 21 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Morphine
Morphine injection 10 mg/70kg
干预措施: Morphine (Drug)
Placebo
Saline injection
干预措施: Placebo (Drug)
结局指标
主要结局
11C Raclopride Binding Potential in Nucleus Accumbens
时间窗: 90 minutes following injection
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
11C Raclopride Binding Potential in Ventral Pallidum
时间窗: 90 minutes following injection
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
11C Raclopride Binding Potential in Caudate
时间窗: 90 minutes following injection
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
11C Raclopride Binding Potential in Putamen
时间窗: 90 minutes following injection
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
次要结局
- Subjective Perception of Morphine Effect - Feel Drug(60 minutes following injection)
- Subjective Perception of Morphine Effect - Feel High(60 minutes following injection)
- Subjective Perception of Morphine Effect - Like Drug(60 minutes following injection)
- Subjective Perception of Morphine Effect - Want More(60 minutes following injection)