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

Primary Purpose

Alcohol Dependence

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
D-Cycloserine PO and Glycine IV
Placebo D-Cycloserine PO and placebo Glycine IV
Placebo D-Cycloserine PO and Glycine IV
D-Cycloserine PO and placebo Glycine IV
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Alcohol Dependence focused on measuring Alcohol Dependence, Alcoholism, Glycine, D-Cycloserine

Eligibility Criteria

21 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion / Exclusion Criteria Alcoholic subjects:

  • Male or female (post-menopausal, surgically sterile, or negative pregnancy test at screening and agreement to utilize an established birth control during the testing period) between the age of 21 and 70 yrs.
  • Meet Diagnostic and Statistical Manual (DSM) IV criteria for alcohol dependence by structured clinical interview
  • Meet von Knorring criteria for early onset (type II) alcoholism
  • Without other DSM IV Axis I diagnoses by Structured Clinical Interview (SCID).
  • Without lifetime history of other substance abuse diagnosis by SCID (excluding tobacco) and urine toxicology screen negative for drug of abuse.
  • Medically and neurologically healthy on the basis of history, physical examination, sequential multiple analysis-computer (SMAC-20), complete blood count (CBC) w/diff. and EKG. In light of the proximity to alcohol dependence, liver function test (LFT) elevations of twice normal will be accepted into the study.
  • Patients with stable medical problems may be included in the study if their medications have not been adjusted in the month prior to participation and if these medications lack prominent central nervous system (CNS) effects.
  • Absence of alcohol within the past 15 days.
  • Patients must be free of medications utilized to facilitate detoxification (lorazepam, oxazepam) for at least 3 days prior to initiating testing.
  • Patients must have no history of alcoholic hallucinosis.
  • Patients must not be in acute alcohol withdrawal as evidence by a score no more than 2 for each item of the Clinical Institute Withdrawal Assessment Scale
  • Patients taking ethionamide or isoniazid will be not be allowed to participate in the study.

Inclusion / Exclusion Criteria Healthy subjects:

  • Male or female (post-menopausal, surgically sterile, or negative pregnancy test at screening and agreement to utilize an established birth control during the testing period) between the age of 21 and 70 yrs.
  • Absence of a lifetime substance abuse diagnosis by the non-patient version of the SCID.
  • Medically and neurologically healthy on the basis of history, physical examination, SMAC-20, CBC w/diff. and EKG. In light of the proximity to alcohol dependence, LFT elevations of twice normal will be accepted into the study.
  • Absence of alcohol within the past 14 days
  • Healthy subjects will be matched to the patient group for age, sex and educational level.

Sites / Locations

  • VA Connecticut Healthcare System

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Alcohol dependent

Healthy subjects

Arm Description

Alcohol dependent patients will receive 4 interventions

Healthy subjects will receive 4 interventions

Outcomes

Primary Outcome Measures

Visual Analog Scales of Similarity to Alcohol - 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
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
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
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
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

Number of Drinks Felt Consumed at 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
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 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
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
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
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
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
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
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
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
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Visual Analog Scales (VAS) - 30 Minutes
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Visual Analog Scales (VAS) - 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
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
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
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: - 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
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 - 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
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
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
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
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
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
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
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 - 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
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
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
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
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
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
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
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
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
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
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
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
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
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)

Full Information

First Posted
March 6, 2008
Last Updated
December 14, 2016
Sponsor
Yale University
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1. Study Identification

Unique Protocol Identification Number
NCT00635102
Brief Title
Glycine and Oral D-Cycloserine in Alcoholic Patients and Healthy Subjects
Official Title
Glycine and Oral D-Cycloserine in Alcoholic Patients and Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
October 1997 (undefined)
Primary Completion Date
February 2008 (Actual)
Study Completion Date
February 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Dependence
Keywords
Alcohol Dependence, Alcoholism, Glycine, D-Cycloserine

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alcohol dependent
Arm Type
Active Comparator
Arm Description
Alcohol dependent patients will receive 4 interventions
Arm Title
Healthy subjects
Arm Type
Active Comparator
Arm Description
Healthy subjects will receive 4 interventions
Intervention Type
Drug
Intervention Name(s)
D-Cycloserine PO and Glycine IV
Other Intervention Name(s)
Glycine infusion, Cycloserine
Intervention Description
Test days will involve administration of D-Cycloserine in the morning in pill form then 4 hours later a 30 minute infusion of Glycine.
Intervention Type
Drug
Intervention Name(s)
Placebo D-Cycloserine PO and placebo Glycine IV
Other Intervention Name(s)
placebo
Intervention Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Placebo D-Cycloserine PO and Glycine IV
Intervention Type
Drug
Intervention Name(s)
D-Cycloserine PO and placebo Glycine IV
Primary Outcome Measure Information:
Title
Visual Analog Scales of Similarity to Alcohol - Baseline
Description
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
Time Frame
Baseline
Title
Visual Analog Scales of Similarity to Alcohol 60 Minutes Prior to Glycine Infusion
Description
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
Time Frame
60 minutes prior to Glycine infusion
Title
Visual Analog Scales of Similarity to Alcohol 30 Minutes
Description
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
Time Frame
30 minutes
Title
Visual Analog Scales of Similarity to Alcohol 60 Minutes
Description
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
Time Frame
60 minutes
Title
Visual Analog Scales of Similarity to Alcohol 120 Minutes
Description
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
Time Frame
120 minutes
Secondary Outcome Measure Information:
Title
Number of Drinks Felt Consumed at 60 Minutes Prior to Glycine Infusion
Description
The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
Time Frame
60 minutes prior to Glycine infusion
Title
Number of Drinks Felt Consumed at 30 Minutes
Description
The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
Time Frame
30 minutes
Title
Number of Drinks Felt Consumed at 60 Minutes
Description
The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
Time Frame
60 minutes
Title
Number of Drinks Felt Consumed at 120 Minutes
Description
The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
Time Frame
120 minutes
Title
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - Baseline
Description
Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
Time Frame
Baseline
Title
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation 60 Minutes Prior to Glycine Infusion
Description
Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
Time Frame
60 minutes prior to Glycine infusion
Title
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 30 Minutes
Description
Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
Time Frame
30 minutes
Title
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 60 Minutes
Description
Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
Time Frame
60 minutes
Title
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 120 Minutes
Description
Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
Time Frame
120 minutes
Title
Visual Analog Scales (VAS) - Baseline
Description
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Time Frame
Baseline
Title
Visual Analog Scales (VAS) - 60 Minutes Prior to Glycine Infusion
Description
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Time Frame
60 minutes prior to Glycine infusion
Title
Visual Analog Scales (VAS) - 30 Minutes
Description
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Time Frame
30 minutes
Title
Visual Analog Scales (VAS) - 60 Minutes
Description
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Time Frame
60 minutes
Title
Visual Analog Scales (VAS) - 120 Minutes
Description
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Time Frame
120 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Desire to Drink- Baseline
Description
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)
Time Frame
Baseline
Title
Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes Prior to Glycine Infusion
Description
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)
Time Frame
60 minutes prior to Glycine infusion
Title
Alcohol Craving Scale (ACS) Subscale: Desire to Drink: - 30 Minutes
Description
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)
Time Frame
30 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes
Description
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)
Time Frame
60 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 120 Minutes
Description
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)
Time Frame
120 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - Baseline
Description
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)
Time Frame
Baseline
Title
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes Prior to Glycine Infusion
Description
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)
Time Frame
60 minutes prior to Glycine infusion
Title
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 30 Minutes
Description
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)
Time Frame
30 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes
Description
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)
Time Frame
60 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 120 Minutes
Description
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)
Time Frame
120 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Discomfort - Baseline
Description
Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
Time Frame
Baseline
Title
Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes Prior to Glycine Infusion
Description
Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
Time Frame
60 minutes prior to Glycine infusion
Title
Alcohol Craving Scale (ACS) Subscale: Discomfort - 30 Minutes
Description
Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
Time Frame
30 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes
Description
Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
Time Frame
60 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Discomfort - 120 Minutes
Description
Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
Time Frame
120 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - Baseline
Description
Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
Time Frame
Baseline
Title
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes Prior to Glycine Infusion
Description
Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
Time Frame
60 minutes prior to Glycine infusion
Title
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 30 Minutes
Description
Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
Time Frame
30 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes
Description
Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
Time Frame
60 minutes
Title
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 120 Minutes
Description
Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
Time Frame
120 minutes
Title
Continuous Performance Task (CPT) - Distractibility A-Prime - 30 Minutes
Description
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)
Time Frame
30 minutes
Title
Continuous Performance Task (CPT) - Vigilance - A-Prime Score 30 Minutes
Description
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)
Time Frame
30 minutes
Title
Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 1
Description
Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 No words recalled - 12 all words recalled)
Time Frame
60 minutes - Trial 1
Title
Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 2
Description
Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 No words recalled - 12 all words recalled)
Time Frame
60 minutes - Trial 2
Title
Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 3
Description
Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 No words recalled - 12 all words recalled)
Time Frame
60 minutes - Trial 3
Title
Hopkins Verbal Learning Task - Delay Recall - 90 Minutes
Description
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)
Time Frame
90 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion / Exclusion Criteria Alcoholic subjects: Male or female (post-menopausal, surgically sterile, or negative pregnancy test at screening and agreement to utilize an established birth control during the testing period) between the age of 21 and 70 yrs. Meet Diagnostic and Statistical Manual (DSM) IV criteria for alcohol dependence by structured clinical interview Meet von Knorring criteria for early onset (type II) alcoholism Without other DSM IV Axis I diagnoses by Structured Clinical Interview (SCID). Without lifetime history of other substance abuse diagnosis by SCID (excluding tobacco) and urine toxicology screen negative for drug of abuse. Medically and neurologically healthy on the basis of history, physical examination, sequential multiple analysis-computer (SMAC-20), complete blood count (CBC) w/diff. and EKG. In light of the proximity to alcohol dependence, liver function test (LFT) elevations of twice normal will be accepted into the study. Patients with stable medical problems may be included in the study if their medications have not been adjusted in the month prior to participation and if these medications lack prominent central nervous system (CNS) effects. Absence of alcohol within the past 15 days. Patients must be free of medications utilized to facilitate detoxification (lorazepam, oxazepam) for at least 3 days prior to initiating testing. Patients must have no history of alcoholic hallucinosis. Patients must not be in acute alcohol withdrawal as evidence by a score no more than 2 for each item of the Clinical Institute Withdrawal Assessment Scale Patients taking ethionamide or isoniazid will be not be allowed to participate in the study. Inclusion / Exclusion Criteria Healthy subjects: Male or female (post-menopausal, surgically sterile, or negative pregnancy test at screening and agreement to utilize an established birth control during the testing period) between the age of 21 and 70 yrs. Absence of a lifetime substance abuse diagnosis by the non-patient version of the SCID. Medically and neurologically healthy on the basis of history, physical examination, SMAC-20, CBC w/diff. and EKG. In light of the proximity to alcohol dependence, LFT elevations of twice normal will be accepted into the study. Absence of alcohol within the past 14 days Healthy subjects will be matched to the patient group for age, sex and educational level.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John H Krystal, M.D.
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Connecticut Healthcare System
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21124304
Citation
Krystal JH, Petrakis IL, Limoncelli D, Nappi SK, Trevisan L, Pittman B, D'Souza DC, Suckow RF. Characterization of the interactive effects of glycine and D-cycloserine in men: further evidence for enhanced NMDA receptor function associated with human alcohol dependence. Neuropsychopharmacology. 2011 Feb;36(3):701-10. doi: 10.1038/npp.2010.203. Epub 2010 Dec 1. Erratum In: Neuropsychopharmacology. 2011 Mar;36(4):911. Suckow, Raymond F [added].
Results Reference
result

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

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