Alcohol DependenceNCT00635102
Glycine and Oral D-Cycloserine in Alcoholic Patients and Healthy Subjects
A study testing D-Cycloserine PO and Glycine IV in people with Alcohol Dependence, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcohol Dependence
- What is being tested?
- D-Cycloserine PO and Glycine IV
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 1997to Feb 2008
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Connecticut Healthcare System
West Haven, Connecticut, 06516
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Alcohol Dependence
- Being tested
- 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
- Keywords
- Alcohol Dependence, Alcoholism, Glycine, D-Cycloserine
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-Cycloserine PO and Glycine IVDrug
Also called Glycine infusion, Cycloserine
Test days will involve administration of D-Cycloserine in the morning in pill form then 4 hours later a 30 minute infusion of Glycine.
Placebo D-Cycloserine PO and placebo Glycine IVDrug
Also called placebo
Placebo
Placebo D-Cycloserine PO and Glycine IVDrug
D-Cycloserine PO and placebo Glycine IVDrug
| Study group | Role | What they receive |
|---|---|---|
| Alcohol dependent | Active comparator | Alcohol dependent patients will receive 4 interventions Receives: 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 |
| Healthy subjects | Active comparator | Healthy subjects will receive 4 interventions Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline
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
Measured: 60 minutes prior to Glycine infusion
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
Measured: 30 minutes
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
Measured: 60 minutes
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
Measured: 120 minutes
Secondary outcomes (40)
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.
Measured: 60 minutes prior to Glycine infusion
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.
Measured: 30 minutes
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.
Measured: 60 minutes
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.
Measured: 120 minutes
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
Measured: Baseline
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
Measured: 60 minutes prior to Glycine infusion
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
Measured: 30 minutes
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
Measured: 60 minutes
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
Measured: 120 minutes
Visual Analog Scales (VAS) - Baseline
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Measured: Baseline
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)
Measured: 60 minutes prior to Glycine infusion
Visual Analog Scales (VAS) - 30 Minutes
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Measured: 30 minutes
Visual Analog Scales (VAS) - 60 Minutes
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Measured: 60 minutes
Visual Analog Scales (VAS) - 120 Minutes
Visual Analog Scales (VAS): Self-report rating scale used to measure high (0 not at all - 7 extremely)
Measured: 120 minutes
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)
Measured: Baseline
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)
Measured: 60 minutes prior to Glycine infusion
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)
Measured: 30 minutes
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)
Measured: 60 minutes
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)
Measured: 120 minutes
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)
Measured: Baseline
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)
Measured: 60 minutes prior to Glycine infusion
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)
Measured: 30 minutes
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)
Measured: 60 minutes
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)
Measured: 120 minutes
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)
Measured: Baseline
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)
Measured: 60 minutes prior to Glycine infusion
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)
Measured: 30 minutes
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)
Measured: 60 minutes
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)
Measured: 120 minutes
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)
Measured: Baseline
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)
Measured: 60 minutes prior to Glycine infusion
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)
Measured: 30 minutes
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)
Measured: 60 minutes
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)
Measured: 120 minutes
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)
Measured: 30 minutes
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)
Measured: 30 minutes
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)
Measured: 60 minutes - Trial 1
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)
Measured: 60 minutes - Trial 2
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)
Measured: 60 minutes - Trial 3
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)
Measured: 90 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2008 (estimated)
- Study startOct 1997
- Primary completionFeb 2008
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alcohol DependenceStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John H Krystal, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00635102
- Sponsor's protocol ID
- 12449
- Other IDs
- VA Merit Grant
- Status last verified
- Dec 2016
- First submitted
- 6 Mar 2008
- Last updated
- 16 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 21124304
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glycine and Oral D-Cycloserine in Alcoholic Patients and Healthy Subjects
- ClinicalTrials.gov ID
- NCT00635102
- Acronym / sponsor ID
- 12449
- Conditions
- Alcohol Dependence
- Keywords
- Alcohol Dependence, Alcoholism, Glycine, D-Cycloserine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Oct 1997
- Primary completion
- Feb 2008 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 13 Mar 2008 (estimated)
- Results
- Posted 16 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alcohol dependent | Active comparator | 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 IVAlcohol dependent patients will receive 4 interventions |
| Healthy subjects | Active comparator | 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 IVHealthy subjects will receive 4 interventions |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-Cycloserine PO and Glycine IVAlso: Glycine infusion, CycloserineTest days will involve administration of D-Cycloserine in the morning in pill form then 4 hours later a 30 minute infusion of Glycine. | Drug | Alcohol dependent, Healthy subjects |
| Placebo D-Cycloserine PO and placebo Glycine IVAlso: placeboPlacebo | Drug | Alcohol dependent, Healthy subjects |
| Placebo D-Cycloserine PO and Glycine IV | Drug | Alcohol dependent, Healthy subjects |
| D-Cycloserine PO and placebo Glycine IV | Drug | Alcohol dependent, Healthy subjects |
Primary outcome
Visual Analog Scales of Similarity to Alcohol - Baseline
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
40 secondary outcomes
Number of Drinks Felt Consumed at 60 Minutes Prior to Glycine Infusion
Time frame: 60 minutes prior to Glycine infusion
Number of Drinks Felt Consumed at 30 Minutes
Time frame: 30 minutes
Number of Drinks Felt Consumed at 60 Minutes
Time frame: 60 minutes
Number of Drinks Felt Consumed at 120 Minutes
Time frame: 120 minutes
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - Baseline
Time frame: Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation 60 Minutes Prior to Glycine Infusion
Time frame: 60 minutes prior to Glycine infusion
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 30 Minutes
Time frame: 30 minutes
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 60 Minutes
Time frame: 60 minutes
Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 120 Minutes
Time frame: 120 minutes
Visual Analog Scales (VAS) - Baseline
Time frame: Baseline
Visual Analog Scales (VAS) - 60 Minutes Prior to Glycine Infusion
Time frame: 60 minutes prior to Glycine infusion
Visual Analog Scales (VAS) - 30 Minutes
Time frame: 30 minutes
Visual Analog Scales (VAS) - 60 Minutes
Time frame: 60 minutes
Visual Analog Scales (VAS) - 120 Minutes
Time frame: 120 minutes
Alcohol Craving Scale (ACS) Subscale: Desire to Drink- Baseline
Time frame: Baseline
Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes Prior to Glycine Infusion
Time frame: 60 minutes prior to Glycine infusion
Alcohol Craving Scale (ACS) Subscale: Desire to Drink: - 30 Minutes
Time frame: 30 minutes
Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes
Time frame: 60 minutes
Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 120 Minutes
Time frame: 120 minutes
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - Baseline
Time frame: Baseline
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes Prior to Glycine Infusion
Time frame: 60 minutes prior to Glycine infusion
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 30 Minutes
Time frame: 30 minutes
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes
Time frame: 60 minutes
Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 120 Minutes
Time frame: 120 minutes
Alcohol Craving Scale (ACS) Subscale: Discomfort - Baseline
Time frame: Baseline
Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes Prior to Glycine Infusion
Time frame: 60 minutes prior to Glycine infusion
Alcohol Craving Scale (ACS) Subscale: Discomfort - 30 Minutes
Time frame: 30 minutes
Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes
Time frame: 60 minutes
Alcohol Craving Scale (ACS) Subscale: Discomfort - 120 Minutes
Time frame: 120 minutes
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - Baseline
Time frame: Baseline
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes Prior to Glycine Infusion
Time frame: 60 minutes prior to Glycine infusion
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 30 Minutes
Time frame: 30 minutes
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes
Time frame: 60 minutes
Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 120 Minutes
Time frame: 120 minutes
Continuous Performance Task (CPT) - Distractibility A-Prime - 30 Minutes
Time frame: 30 minutes
Continuous Performance Task (CPT) - Vigilance - A-Prime Score 30 Minutes
Time frame: 30 minutes
Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 1
Time frame: 60 minutes - Trial 1
Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 2
Time frame: 60 minutes - Trial 2
Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 3
Time frame: 60 minutes - Trial 3
Hopkins Verbal Learning Task - Delay Recall - 90 Minutes
Time frame: 90 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21124304Krystal 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John H Krystal, M.D. principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing D-Cycloserine PO and Glycine IV in people with Alcohol Dependence, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Analog Scales of Similarity to Alcohol - Baseline (time frame: Baseline). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00635102, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2016.