Glycine and Oral D-Cycloserine in Alcoholic Patients and Healthy Subjects

Not Applicable

Completed

Conditions: Alcohol Dependence

Interventions: Drug: D-Cycloserine PO and Glycine IV
Drug: Placebo D-Cycloserine PO and placebo Glycine IV
Drug: Placebo D-Cycloserine PO and Glycine IV
Drug: D-Cycloserine PO and placebo Glycine IV

Registration Number: NCT00635102

Lead Sponsor: Yale University

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 57

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Healthy subjects	D-Cycloserine PO and placebo Glycine IV	Healthy subjects will receive 4 interventions
Healthy subjects	D-Cycloserine PO and Glycine IV	Healthy subjects will receive 4 interventions
Alcohol dependent	D-Cycloserine PO and Glycine IV	Alcohol dependent patients will receive 4 interventions
Alcohol dependent	Placebo D-Cycloserine PO and Glycine IV	Alcohol dependent patients will receive 4 interventions
Alcohol dependent	D-Cycloserine PO and placebo Glycine IV	Alcohol dependent patients will receive 4 interventions
Healthy subjects	Placebo D-Cycloserine PO and Glycine IV	Healthy subjects will receive 4 interventions
Alcohol dependent	Placebo D-Cycloserine PO and placebo Glycine IV	Alcohol dependent patients will receive 4 interventions
Healthy subjects	Placebo D-Cycloserine PO and placebo Glycine IV	Healthy subjects will receive 4 interventions

Primary Outcome Measures

Name	Time	Method
Visual Analog Scales of Similarity to Alcohol - Baseline	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	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	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	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	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

Secondary Outcome Measures

Name	Time	Method
Number of Drinks Felt Consumed at 60 Minutes Prior to Glycine Infusion	60 minutes prior to Glycine infusion	The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
Number of Drinks Felt Consumed at 30 Minutes	30 minutes	The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
Visual Analog Scales (VAS) - 60 Minutes	60 minutes	Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Visual Analog Scales (VAS) - 120 Minutes	120 minutes	Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Alcohol Craving Scale (ACS) Subscale: Desire to Drink- Baseline	Baseline	Alcohol Craving Scale (ACS) Subscale: Desire to drink: Self-report rating scale used to measure desire to drink alcohol (0 No desire to drink alcohol - 100 Definitely desire to drink alcohol)
Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes Prior to Glycine Infusion	60 minutes prior to Glycine infusion	Alcohol Craving Scale (ACS) Subscale: Desire to drink: Self-report rating scale used to measure desire to drink alcohol (0 No desire to drink alcohol - 100 Definitely desire to drink alcohol)
Number of Drinks Felt Consumed at 60 Minutes	60 minutes	The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
Number of Drinks Felt Consumed at 120 Minutes	120 minutes	The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - Baseline	Baseline	Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation 60 Minutes Prior to Glycine Infusion	60 minutes prior to Glycine infusion	Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 30 Minutes	30 minutes	Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 60 Minutes	60 minutes	Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 120 Minutes	120 minutes	Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
Visual Analog Scales (VAS) - Baseline	Baseline	Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Visual Analog Scales (VAS) - 60 Minutes Prior to Glycine Infusion	60 minutes prior to Glycine infusion	Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Visual Analog Scales (VAS) - 30 Minutes	30 minutes	Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 120 Minutes	120 minutes	Alcohol Craving Scale (ACS) Subscale: Desire to drink: Self-report rating scale used to measure desire to drink alcohol (0 No desire to drink alcohol - 100 Definitely desire to drink alcohol)
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - Baseline	Baseline	Alcohol Craving Scale (ACS) Subscale: Mood improvement : Self-report rating scale used to measure expected alcohol-related mood improvement (0 Not at all - 100 Definitely)
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 : Self-report rating scale used to measure expected alcohol-related mood improvement (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 30 Minutes	30 minutes	Alcohol Craving Scale (ACS) Subscale: Mood improvement : Self-report rating scale used to measure expected alcohol-related mood improvement (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes	60 minutes	Alcohol Craving Scale (ACS) Subscale: Mood improvement : Self-report rating scale used to measure expected alcohol-related mood improvement (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 120 Minutes	120 minutes	Alcohol Craving Scale (ACS) Subscale: Mood improvement : Self-report rating scale used to measure expected alcohol-related mood improvement (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Discomfort - Baseline	Baseline	Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes Prior to Glycine Infusion	60 minutes prior to Glycine infusion	Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Desire to Drink: - 30 Minutes	30 minutes	Alcohol Craving Scale (ACS) Subscale: Desire to drink: Self-report rating scale used to measure desire to drink alcohol (0 No desire to drink alcohol - 100 Definitely desire to drink alcohol)
Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes	60 minutes	Alcohol Craving Scale (ACS) Subscale: Desire to drink: Self-report rating scale used to measure desire to drink alcohol (0 No desire to drink alcohol - 100 Definitely desire to drink alcohol)
Alcohol Craving Scale (ACS) Subscale: Discomfort - 30 Minutes	30 minutes	Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes	60 minutes	Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Discomfort - 120 Minutes	120 minutes	Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - Baseline	Baseline	Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
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: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 30 Minutes	30 minutes	Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes	60 minutes	Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 120 Minutes	120 minutes	Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
Continuous Performance Task (CPT) - Distractibility A-Prime - 30 Minutes	30 minutes	gordon diagnostic system is a continuous performance task (CPT) to measure distractibility - (A-Prime score range 0 minimum - 1 maximum - the higher number the better the performance)
Continuous Performance Task (CPT) - Vigilance - A-Prime Score 30 Minutes	30 minutes	gordon diagnostic system is a continuous performance task (CPT) to measure Vigilance - (A-Prime score range 0 minimum - 1 maximum - The higher number the better the performance)
Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 1	60 minutes - Trial 1	Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 No words recalled - 12 all words recalled)
Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 2	60 minutes - Trial 2	Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 No words recalled - 12 all words recalled)
Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 3	60 minutes - Trial 3	Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 No words recalled - 12 all words recalled)
Hopkins Verbal Learning Task - Delay Recall - 90 Minutes	90 minutes	Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (delay recall - 30 minutes after Trials 1-3 were given) (0 No words recalled - 12 all words recalled)