Facilitation of NMDA Receptor Function in Patients With Schizophrenia and Co-morbid Alcoholism
Condition: Alcoholism; Schizophrenia
MeSH terms: Alcoholism; Schizophrenia
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): Glycine; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Glycine, 0.8 gr per kg given in two daily doses
Intervention MeSH terms: Glycine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: glycine; treatment; alcohol dependence; schizophrenia