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Trial record 28 of 2455 for:    NMDA

Facilitation of NMDA Receptor Function in Patients With Schizophrenia and Co-morbid Alcoholism

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ClinicalTrials.gov Identifier: NCT00338598
Recruitment Status : Completed
First Posted : June 20, 2006
Results First Posted : April 12, 2017
Last Update Posted : January 17, 2018
Sponsor:
Collaborator:
Stanley Medical Research Institute
Information provided by (Responsible Party):
Yale University

Brief Summary:

This placebo-controlled study is designed to evaluate the efficacy of glycine, an agonist of the glycine-B co-agonist site of the NMDA receptor, on alcohol consumption and craving as well as negative symptoms in schizophrenia.

Glycine will decrease the rewarding action of ethanol and reduce ethanol consumption. Also, glycine will improve negative symptoms and cognitive deficits in schizophrenia.


Condition or disease Intervention/treatment Phase
Alcoholism Schizophrenia Drug: Glycine Drug: placebo Phase 2

Detailed Description:

OBJECTIVE: Schizophrenia affects about 1% of the general population and is a highly disabling disease. Additionally, the rate of alcohol dependency for patients with schizophrenia is very high. There are no established treatments for alcohol dependency and negative symptoms in schizophrenia. This study will examine whether the addition of glycine to neuroleptic medications will help patients with schizophrenia and alcoholism decrease their drinking as well as improve negative symptoms.

RESEARCH PLAN: An abnormality of the glutamate neurotransmitter system has been hypothesized for both alcoholism and schizophrenia. Studies suggest that the amino acid glycine may improve alcohol dependency and symptoms of schizophrenia by acting on the N methyl D aspartate (NMDA) glutamate receptor. Glycine causes reversal of the effects of ethanol in animal studies and improves mood, social withdrawal and other so called "negative symptoms" of schizophrenia. Consequently, the use of glycine by patients with schizophrenia and alcohol dependency may potentially decrease alcohol craving and alcohol consumption and also improve certain symptoms of schizophrenia. The potential of glycine to improve both alcohol dependency and negative symptoms could represent an important step in the improvement of the quality of life for patients with schizophrenia.

METHODOLOGY/FINDINGS/RESULTS: In order to test this hypothesis, we will use a double blind, placebo controlled study and measure the number of drinks, the degree of craving for alcohol and symptoms of schizophrenia among other parameters. Our principal approach to analyses of medication effectiveness will be the application of the linear mixed effect model. The linear mixed effect model permits a flexible approach for studying change in individuals through time as a random effect, and does not require all patients to have data at all measured points. Our principal model of analysis includes treatment (placebo or glycine), as between subject factor, and time, as within subject factor. Compliance will be also included as a time varying independent variable. This project continues to recruit subjects.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Facilitation of NMDA Receptor Function in Patients With Schizophrenia and Co-morbid Alcoholism
Study Start Date : June 2003
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Glycine

Arm Intervention/treatment
Experimental: Glycine
Glycine, 0.8 gr per kg given in two daily doses
Drug: Glycine
Glycine, 0.8 gr per kg given in two daily doses

Placebo Comparator: placebo
placebo will be administered.
Drug: placebo



Primary Outcome Measures :
  1. Self Reported Weekly Alcohol Consumption [ Time Frame: 12 weeks ]
    Percentage of drinking days and heavy drinking days using timeline follow back

  2. Self Reported Weekly Alcohol Craving [ Time Frame: 12 weeks ]
    The Obsessive Compulsive Drinking Scale (OCDS) is consisted by 14 items rated 0 - 4. The minimum and maximum values possibly obtained in this scale are respectively 0 and 56, this last one, meaning the most craving possible experienced. It is a short and easy to administer scale (average of 5 minutes per self-rating), built to measure severity and improvement during alcoholism treatment trials.

  3. Weekly Ratings of Negative/Positive Psychotic Symptoms [ Time Frame: 12 weeks ]
    The PANSS or the Positive and Negative Syndrome Scale is a medical scale used for measuring symptom severity of patients with schizophrenia. The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers. Of the 30 items included in the PANSS, 7 constitute a Positive Scale, 7 a Negative Scale, and the remaining 16 a General Psychopathology Scale.The scores for these scales are arrived at by summation of ratings across component items. Therefore, the potential ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. A higher score indicates more severe symptoms for each scale.

  4. Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) [ Time Frame: 12 weeks ]
    Hopkins Verbal Learning Test Assesses short term verbal learning and memory. Subscales include immediate recall (0-36), delayed recall (0-12) , and recognition (0-12). A higher score indicates better memory performance.


Secondary Outcome Measures :
  1. Weekly Drug Use [ Time Frame: 12 weeks ]
  2. Baseline and End of Treatment Quality of Life [ Time Frame: 12 weeks ]
  3. Baseline and End of Treatment Neurophysiological Measures [ Time Frame: 12 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DSM-IV diagnosis of schizophrenia or schizoaffective disorder
  • DSM-IV diagnosis of alcohol dependence
  • Stable treatment with typical or atypical antipsychotics

Exclusion Criteria:

  • Axis I diagnosis other than alcohol dependence, schizophrenia, schizoaffective disorder, OCD, and PTSD.
  • current drug dependence
  • evidence of significant hepatocellular injury evidence by abnormal SGOT or SGPT levels
  • history of seizures
  • diabetes and medical conditions that would alter glycine metabolism
  • positive pregnancy test
  • treatment with clozapine, naltrexone or disulfiram

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00338598


Locations
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United States, Connecticut
VA Connecticut Healthcare System
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
Stanley Medical Research Institute
Investigators
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Principal Investigator: Ismene Petrakis, M.D. Yale University

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00338598     History of Changes
Other Study ID Numbers: 20915
First Posted: June 20, 2006    Key Record Dates
Results First Posted: April 12, 2017
Last Update Posted: January 17, 2018
Last Verified: January 2018

Keywords provided by Yale University:
glycine
treatment
alcohol dependence
schizophrenia

Additional relevant MeSH terms:
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Schizophrenia
Alcoholism
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Glycine
Glycine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs