Clinical trial NCT00338598: Facilitation of NMDA Receptor Function in Patients With Schizophrenia and Co-morbid Alcoholism
Official title: Facilitation of NMDA Receptor Function in Patients With Schizophrenia and Co-morbid Alcoholism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcoholism
Schizophrenia
Keywords: glycine
treatment
alcohol dependence
schizophrenia
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2006-06-20
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Self Reported Weekly Alcohol Consumption
timeFrame: 12 weeks
measure: Self Reported Weekly Alcohol Craving
timeFrame: 12 weeks
measure: Weekly Ratings of Negative/Positive Psychotic Symptoms
timeFrame: 12 weeks
measure: Baseline and End of Treatment Cognitive Functioning Measures (Hopkins)
timeFrame: 12 weeks
Secondary outcomes:
measure: Weekly Drug Use
timeFrame: 12 weeks
measure: Baseline and End of Treatment Quality of Life
timeFrame: 12 weeks
measure: Baseline and End of Treatment Neurophysiological Measures
timeFrame: 12 weeks
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
affiliation: Yale University
name: Ismene Petrakis, M.D.
role: PRINCIPAL_INVESTIGATOR
References: