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

NCT00635102 | Completed Results

• 2 other identifiers: 12449VA Merit Grant
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcohol Dependence

Keywords

Alcohol Dependence, Alcoholism, Glycine, D-Cycloserine

Outcome Measures

Primary Outcomes (5)

• 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

  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

  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

  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

  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

  120 minutes

Secondary Outcomes (40)

• Number of Drinks Felt Consumed at 60 Minutes Prior to Glycine Infusion

  60 minutes prior to Glycine infusion

• Number of Drinks Felt Consumed at 30 Minutes

  30 minutes

• Number of Drinks Felt Consumed at 60 Minutes

  60 minutes

• Number of Drinks Felt Consumed at 120 Minutes

  120 minutes

• Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - Baseline

  Baseline

Study Arms (2)

Alcohol dependent

ACTIVE COMPARATOR

Alcohol dependent patients will receive 4 interventions

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

Healthy subjects

ACTIVE COMPARATOR

Healthy subjects will receive 4 interventions

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

Interventions

D-Cycloserine PO and Glycine IV DRUG

Test days will involve administration of D-Cycloserine in the morning in pill form then 4 hours later a 30 minute infusion of Glycine.

Also known as: Glycine infusion, Cycloserine

Alcohol dependent; Healthy subjects

Placebo D-Cycloserine PO and placebo Glycine IV DRUG

Placebo

Also known as: placebo

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

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

Related Publications (1)

• 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.

  PMID: 21124304 RESULT

MeSH Terms

Conditions

Alcoholism

Interventions

Cycloserine

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr John Krystal
• Organization: Yale University School of Medicine

john.krystal@yale.edu

203-785-6396

Study Officials

• John H Krystal, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2008
• First Posted: March 13, 2008
• Study Start: October 1, 1997
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: December 16, 2016
• Results First Posted: December 16, 2016

Record last verified: 2016-12

Locations

US (1)