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Facilitation of NMDA Receptor Function in Patients With Schizophrenia and Co-morbid Alcoholism
This study is ongoing, but not recruiting participants.

First Received on June 15, 2006.   Last Updated on January 26, 2012   History of Changes
Sponsor: Elizabeth Ralevski
Collaborator: Stanley Medical Research Institute
Information provided by (Responsible Party): Elizabeth Ralevski, Yale University
ClinicalTrials.gov Identifier: NCT00338598
  Purpose

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 Intervention Phase
Alcoholism
Schizophrenia
Drug: Glycine
Phase II

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Facilitation of NMDA Receptor Function in Patients With Schizophrenia and Co-morbid Alcoholism

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • self reported weekly alcohol consumption [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • self reported weekly alcohol craving [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • weekly ratings of negative/positive psychotic symptoms [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • baseline and end of treatment cognitive functioning measures [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • weekly drug use [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • baseline and end of treatment quality of life [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • baseline and end of treatment neurophysiological measures [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 46
Study Start Date: June 2003
Estimated Study Completion Date: February 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Glycine
    Glycine, 0.8 gr per kg given in two daily doses
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.

  Eligibility

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00338598

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

No publications provided

Responsible Party: Elizabeth Ralevski, Assistant Professor, Yale University
ClinicalTrials.gov Identifier: NCT00338598     History of Changes
Other Study ID Numbers: HIC # 20915
Study First Received: June 15, 2006
Last Updated: January 26, 2012
Health Authority: United States: Institutional Review Board;   United States: Food and Drug Administration

Keywords provided by Yale University:
glycine
treatment
alcohol dependence
schizophrenia

Additional relevant MeSH terms:
Alcoholism
Schizophrenia
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Glycine
Glycine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012