Glycine and Oral D-Cycloserine in Alcoholic Patients and Healthy Subjects
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Visual Analog Scales of Similarity to Alcohol - Baseline
研究概览
简要总结
Question #1: Will glycine ameliorate cognitive deficits? Hypothesis #1: Based on positive findings conducted with glycine and milacemide, a glycine prodrug, in schizophrenia and dementia, we expect that glycine will ameliorate cognitive deficits.
Question #2: Will alcoholic patients show enhanced endocrinal effects to glycine? Hypothesis #2: Based on the dose-related effects of glycine in healthy subjects, we expect that glycine will increase the endocrinal response to glycine in alcoholic patients with, supposedly, dysregulated NMDA receptor function.
Question #3: Will D-cycloserine have ethanol-like effects? Hypothesis #3: If inhibition of NMDA receptor function is fundamental to the subjective effects of ethanol, then the NMDA antagonist properties of D-cycloserine should be recognized as ethanol-like (relative to placebo) in recently detoxified alcoholics and healthy subjects.
Question #4: Will D-cycloserine reverse cognitive benefits of glycine? Hypothesis 4: Based on the dose related NMDA antagonist activity of D-cycloserine, we expect that D-cycloserine will compete with the agonist activity of glycine and therefore it will reverse the cognitive benefits of glycine.
Question #5: Will D-cycloserine inhibit endocrinal effects of glycine? Hypothesis #5: If the agonist activity of glycine is necessary to determine endocrine response, then the dose-related NMDA antagonist properties of D-cycloserine should block these effects.
详细描述
The purpose of this study is to investigate the interaction between glycine and D-cycloserine in alcoholic patients and healthy subjects. Preclinical studies have shown that compounds acting at the glycine site of the N-methyl-D-aspartate (NMDA) receptor complex, such as glycine, may reverse the effects of ethanol on the NMDA receptor function (Rabe et al., 1990). The amino acid glycine is a co-agonist of the NMDA receptor complex (Kemp et al., 1993). It binds to the strychnine-insensitive site and positively modulates the NMDA receptor (Mc Donald et al., 1990). Physiologically, the glycine site is not saturated, and administration of glycine can potentiate NMDA receptor mediated responses. In contrast, D-cycloserine (Hood et al., 1989) is a partial-agonist at the glycine site of the NMDA receptor, with dose-dependent NMDA antagonist properties. The NMDA antagonist activity of D-cycloserine should produce ethanol like-effects that can be reversed by the agonist glycine. This study is intended to evaluate possible contributions of the glycine site to the reduction of cognitive deficits of alcoholism and complements the current work at VA Connecticut Healthcare System on the NMDA antagonists in alcoholic and healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 70 Years（Adult, Older 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
Alcohol dependent
Alcohol dependent patients will receive 4 interventions
干预措施: D-Cycloserine PO and Glycine IV (Drug)
Alcohol dependent
Alcohol dependent patients will receive 4 interventions
干预措施: Placebo D-Cycloserine PO and placebo Glycine IV (Drug)
Alcohol dependent
Alcohol dependent patients will receive 4 interventions
干预措施: Placebo D-Cycloserine PO and Glycine IV (Drug)
Alcohol dependent
Alcohol dependent patients will receive 4 interventions
干预措施: D-Cycloserine PO and placebo Glycine IV (Drug)
Healthy subjects
Healthy subjects will receive 4 interventions
干预措施: D-Cycloserine PO and Glycine IV (Drug)
Healthy subjects
Healthy subjects will receive 4 interventions
干预措施: Placebo D-Cycloserine PO and placebo Glycine IV (Drug)
Healthy subjects
Healthy subjects will receive 4 interventions
干预措施: Placebo D-Cycloserine PO and Glycine IV (Drug)
Healthy subjects
Healthy subjects will receive 4 interventions
干预措施: D-Cycloserine PO and placebo Glycine IV (Drug)
结局指标
主要结局
Visual Analog Scales of Similarity to Alcohol - Baseline
时间窗: Baseline
Visual Analog Scales of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol -7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Visual Analog Scales of Similarity to Alcohol 60 Minutes Prior to Glycine Infusion
时间窗: 60 minutes prior to Glycine infusion
Visual Analog Scales of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol -7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Visual Analog Scales of Similarity to Alcohol 30 Minutes
时间窗: 30 minutes
Visual Analog Scales of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol -7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Visual Analog Scales of Similarity to Alcohol 60 Minutes
时间窗: 60 minutes
Visual Analog Scales of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol -7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Visual Analog Scales of Similarity to Alcohol 120 Minutes
时间窗: 120 minutes
Visual Analog Scales of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol -7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
次要结局
- Number of Drinks Felt Consumed at 60 Minutes Prior to Glycine Infusion(60 minutes prior to Glycine infusion)
- Number of Drinks Felt Consumed at 30 Minutes(30 minutes)
- Visual Analog Scales (VAS) - 60 Minutes(60 minutes)
- Visual Analog Scales (VAS) - 120 Minutes(120 minutes)
- Alcohol Craving Scale (ACS) Subscale: Desire to Drink- Baseline(Baseline)
- Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes Prior to Glycine Infusion(60 minutes prior to Glycine infusion)
- Number of Drinks Felt Consumed at 60 Minutes(60 minutes)
- Number of Drinks Felt Consumed at 120 Minutes(120 minutes)
- Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - Baseline(Baseline)
- Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation 60 Minutes Prior to Glycine Infusion(60 minutes prior to Glycine infusion)
- Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 30 Minutes(30 minutes)
- Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 60 Minutes(60 minutes)
- Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 120 Minutes(120 minutes)
- Visual Analog Scales (VAS) - Baseline(Baseline)
- Visual Analog Scales (VAS) - 60 Minutes Prior to Glycine Infusion(60 minutes prior to Glycine infusion)
- Visual Analog Scales (VAS) - 30 Minutes(30 minutes)
- Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 120 Minutes(120 minutes)
- Alcohol Craving Scale (ACS) Subscale: Mood Improvement - Baseline(Baseline)
- Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes Prior to Glycine Infusion(60 minutes prior to Glycine infusion)
- Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 30 Minutes(30 minutes)
- Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes(60 minutes)
- Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 120 Minutes(120 minutes)
- Alcohol Craving Scale (ACS) Subscale: Discomfort - Baseline(Baseline)
- Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes Prior to Glycine Infusion(60 minutes prior to Glycine infusion)
- Alcohol Craving Scale (ACS) Subscale: Desire to Drink: - 30 Minutes(30 minutes)
- Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes(60 minutes)
- Alcohol Craving Scale (ACS) Subscale: Discomfort - 30 Minutes(30 minutes)
- Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes(60 minutes)
- Alcohol Craving Scale (ACS) Subscale: Discomfort - 120 Minutes(120 minutes)
- Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - Baseline(Baseline)
- Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes Prior to Glycine Infusion(60 minutes prior to Glycine infusion)
- Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 30 Minutes(30 minutes)
- Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes(60 minutes)
- Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 120 Minutes(120 minutes)
- Continuous Performance Task (CPT) - Distractibility A-Prime - 30 Minutes(30 minutes)
- Continuous Performance Task (CPT) - Vigilance - A-Prime Score 30 Minutes(30 minutes)
- Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 1(60 minutes - Trial 1)
- Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 2(60 minutes - Trial 2)
- Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 3(60 minutes - Trial 3)
- Hopkins Verbal Learning Task - Delay Recall - 90 Minutes(90 minutes)