- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00635102
Glycine and Oral D-Cycloserine in Alcoholic Patients and Healthy Subjects
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.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Connecticut
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West Haven, Connecticut, United States, 06516
- VA Connecticut Healthcare System
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Alcohol dependent
Alcohol dependent patients will receive 4 interventions
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Test days will involve administration of D-Cycloserine in the morning in pill form then 4 hours later a 30 minute infusion of Glycine.
Other Names:
Placebo
Other Names:
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Active Comparator: Healthy subjects
Healthy subjects will receive 4 interventions
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Test days will involve administration of D-Cycloserine in the morning in pill form then 4 hours later a 30 minute infusion of Glycine.
Other Names:
Placebo
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Visual Analog Scales of Similarity to Alcohol - Baseline
Time Frame: Baseline
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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
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Baseline
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Visual Analog Scales of Similarity to Alcohol 60 Minutes Prior to Glycine Infusion
Time Frame: 60 minutes prior to Glycine infusion
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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
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60 minutes prior to Glycine infusion
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Visual Analog Scales of Similarity to Alcohol 30 Minutes
Time Frame: 30 minutes
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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
|
30 minutes
|
Visual Analog Scales of Similarity to Alcohol 60 Minutes
Time Frame: 60 minutes
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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
|
60 minutes
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Visual Analog Scales of Similarity to Alcohol 120 Minutes
Time Frame: 120 minutes
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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
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120 minutes
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Drinks Felt Consumed at 60 Minutes Prior to Glycine Infusion
Time Frame: 60 minutes prior to Glycine infusion
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The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
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60 minutes prior to Glycine infusion
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Number of Drinks Felt Consumed at 30 Minutes
Time Frame: 30 minutes
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The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
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30 minutes
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Number of Drinks Felt Consumed at 60 Minutes
Time Frame: 60 minutes
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The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
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60 minutes
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Number of Drinks Felt Consumed at 120 Minutes
Time Frame: 120 minutes
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The Number of Drinks Scale asks subjects to report on the number of alcoholic drinks they felt they had consumed.
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120 minutes
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Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - Baseline
Time Frame: Baseline
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Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
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Baseline
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Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation 60 Minutes Prior to Glycine Infusion
Time Frame: 60 minutes prior to Glycine infusion
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Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
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60 minutes prior to Glycine infusion
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Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 30 Minutes
Time Frame: 30 minutes
|
Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
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30 minutes
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Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 60 Minutes
Time Frame: 60 minutes
|
Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
|
60 minutes
|
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 120 Minutes
Time Frame: 120 minutes
|
Self-report rating scale used to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol
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120 minutes
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Visual Analog Scales (VAS) - Baseline
Time Frame: Baseline
|
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
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Baseline
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Visual Analog Scales (VAS) - 60 Minutes Prior to Glycine Infusion
Time Frame: 60 minutes prior to Glycine infusion
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Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
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60 minutes prior to Glycine infusion
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Visual Analog Scales (VAS) - 30 Minutes
Time Frame: 30 minutes
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Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
|
30 minutes
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Visual Analog Scales (VAS) - 60 Minutes
Time Frame: 60 minutes
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Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
|
60 minutes
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Visual Analog Scales (VAS) - 120 Minutes
Time Frame: 120 minutes
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Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
|
120 minutes
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Alcohol Craving Scale (ACS) Subscale: Desire to Drink- Baseline
Time Frame: Baseline
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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)
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Baseline
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Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes Prior to Glycine Infusion
Time Frame: 60 minutes prior to Glycine infusion
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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)
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60 minutes prior to Glycine infusion
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Alcohol Craving Scale (ACS) Subscale: Desire to Drink: - 30 Minutes
Time Frame: 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)
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30 minutes
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Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes
Time Frame: 60 minutes
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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)
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60 minutes
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Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 120 Minutes
Time Frame: 120 minutes
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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)
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120 minutes
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Alcohol Craving Scale (ACS) Subscale: Mood Improvement - Baseline
Time Frame: Baseline
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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)
|
Baseline
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Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes Prior to Glycine Infusion
Time Frame: 60 minutes prior to Glycine infusion
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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)
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60 minutes prior to Glycine infusion
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Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 30 Minutes
Time Frame: 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)
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30 minutes
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Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes
Time Frame: 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)
|
60 minutes
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Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 120 Minutes
Time Frame: 120 minutes
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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)
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120 minutes
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Alcohol Craving Scale (ACS) Subscale: Discomfort - Baseline
Time Frame: Baseline
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Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
|
Baseline
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Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes Prior to Glycine Infusion
Time Frame: 60 minutes prior to Glycine infusion
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Alcohol Craving Scale (ACS) Subscale: Discomfort: Self-report rating scale - subscale reflecting expected alcohol-related relief from discomfort (0 Not at all - 100 Definitely)
|
60 minutes prior to Glycine infusion
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Alcohol Craving Scale (ACS) Subscale: Discomfort - 30 Minutes
Time Frame: 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)
|
30 minutes
|
Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes
Time Frame: 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)
|
60 minutes
|
Alcohol Craving Scale (ACS) Subscale: Discomfort - 120 Minutes
Time Frame: 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)
|
120 minutes
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Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - Baseline
Time Frame: Baseline
|
Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
|
Baseline
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Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes Prior to Glycine Infusion
Time Frame: 60 minutes prior to Glycine infusion
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Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
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60 minutes prior to Glycine infusion
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Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 30 Minutes
Time Frame: 30 minutes
|
Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
|
30 minutes
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Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes
Time Frame: 60 minutes
|
Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
|
60 minutes
|
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 120 Minutes
Time Frame: 120 minutes
|
Alcohol Craving Scale (ACS) Subscale: Self-report rating scale used to measure reduced control of alcohol (0 Not at all - 100 Definitely)
|
120 minutes
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Continuous Performance Task (CPT) - Distractibility A-Prime - 30 Minutes
Time Frame: 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)
|
30 minutes
|
Continuous Performance Task (CPT) - Vigilance - A-Prime Score 30 Minutes
Time Frame: 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)
|
30 minutes
|
Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 1
Time Frame: 60 minutes - Trial 1
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Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function.
(Three immediate recall trials) (0 No words recalled - 12 all words recalled)
|
60 minutes - Trial 1
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Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 2
Time Frame: 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)
|
60 minutes - Trial 2
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Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 3
Time Frame: 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)
|
60 minutes - Trial 3
|
Hopkins Verbal Learning Task - Delay Recall - 90 Minutes
Time Frame: 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)
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90 minutes
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: John H Krystal, M.D., Yale University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Alcohol-Related Disorders
- Substance-Related Disorders
- Alcoholism
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antimetabolites
- Anti-Bacterial Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Anti-Infective Agents, Urinary
- Renal Agents
- Glycine Agents
- Cycloserine
- Glycine
Other Study ID Numbers
- 12449
- VA Merit Grant (VA Merit Grant)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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