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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00338598
• Other study ID #: 20915
• Status: Completed
• Phase: Phase 2
• First received: June 15, 2006
• Last updated: January 12, 2018
• Start date: June 2003
• Est. completion date: December 2015

Study information

• Verified date: January 2018
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcoholism
• Schizophrenia

Intervention

Drug:
• Glycine
Glycine, 0.8 gr per kg given in two daily doses
• placebo

Locations

Country	Name	City	State
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Stanley Medical Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Self Reported Weekly Alcohol Consumption	Percentage of drinking days and heavy drinking days using timeline follow back	12 weeks
Primary	Self Reported Weekly Alcohol Craving	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.	12 weeks
Primary	Weekly Ratings of Negative/Positive Psychotic Symptoms	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.	12 weeks
Primary	Baseline and End of Treatment Cognitive Functioning Measures (Hopkins)	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.	12 weeks
Secondary	Weekly Drug Use		12 weeks
Secondary	Baseline and End of Treatment Quality of Life		12 weeks
Secondary	Baseline and End of Treatment Neurophysiological Measures		12 weeks