Alcoholism, Schizophrenia
Conditions
Keywords
glycine, treatment, alcohol dependence, schizophrenia
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.
Interventions
DRUGGlycine
Glycine, 0.8 gr per kg given in two daily doses
DRUGplacebo
Sponsors
Stanley Medical Research Institute
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Self Reported Weekly Alcohol Consumption | 12 weeks | Percentage of drinking days and heavy drinking days using timeline follow back |
| Self Reported Weekly Alcohol Craving | 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. |
| Weekly Ratings of Negative/Positive Psychotic Symptoms | 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. |
| Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | 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
| Measure | Time frame |
|---|---|
| Baseline and End of Treatment Quality of Life | 12 weeks |
| Baseline and End of Treatment Neurophysiological Measures | 12 weeks |
| Weekly Drug Use | 12 weeks |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the VA hospital in West Haven, CT and the Community Mental Health Center in New Haven, CT through word of mouth, advertisement and clinician referrals.
Pre-assignment details
Twenty men, who met DSM IV criteria for schizophrenia or schizoaffective disorder, who also met DSM IV diagnosis of alcohol dependence with at least one recent episode of heavy drinking (defined as more than 5 drinks/drinking episode) over the past 14 days participated in the study. The participants were in stable treatment for at least 2 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Glycine Glycine, 0.8 gr per kg given in two daily doses
Glycine: Glycine, 0.8 gr per kg given in two daily doses | 10 |
| Placebo placebo will be administered.
placebo | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Glycine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 49.2 years STANDARD_DEVIATION 4.8 | 48.6 years STANDARD_DEVIATION 5 | 48.9 years STANDARD_DEVIATION 4.8 |
| Drinks per day | 8.9 drinks per day STANDARD_DEVIATION 8.5 | 5.9 drinks per day STANDARD_DEVIATION 5 | 7.5 drinks per day STANDARD_DEVIATION 7.1 |
| Race/Ethnicity, Customized Black | 3 Participants | 7 Participants | 10 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 3 / 10 | 2 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
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.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glycine | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | Baseline Immediate Recall | 21.8 units on a scale | Standard Error 1.7 |
| Glycine | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | 12 Weeks Immediate Recall | 20.9 units on a scale | Standard Error 1.8 |
| Glycine | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | Baseline Delayed Recall | 6.1 units on a scale | Standard Error 0.9 |
| Glycine | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | 12 Weeks Delayed Recall | 6.6 units on a scale | Standard Error 0.9 |
| Glycine | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | Baseline Recognition | 10.2 units on a scale | Standard Error 1 |
| Glycine | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | 12 Weeks Recognition | 9.8 units on a scale | Standard Error 1 |
| Placebo | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | Baseline Recognition | 12.5 units on a scale | Standard Error 1 |
| Placebo | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | Baseline Immediate Recall | 19.7 units on a scale | Standard Error 1.7 |
| Placebo | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | 12 Weeks Delayed Recall | 6.5 units on a scale | Standard Error 0.9 |
| Placebo | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | 12 Weeks Immediate Recall | 19.5 units on a scale | Standard Error 1.8 |
| Placebo | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | 12 Weeks Recognition | 12.2 units on a scale | Standard Error 1 |
| Placebo | Baseline and End of Treatment Cognitive Functioning Measures (Hopkins) | Baseline Delayed Recall | 6.4 units on a scale | Standard Error 0.9 |
Primary
Self Reported Weekly Alcohol Consumption
Percentage of drinking days and heavy drinking days using timeline follow back
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glycine | Self Reported Weekly Alcohol Consumption | % number of drinking days | 23.4 percentage of days | Standard Error 28.8 |
| Glycine | Self Reported Weekly Alcohol Consumption | % number of heavy drinking days | 15.7 percentage of days | Standard Error 20.8 |
| Placebo | Self Reported Weekly Alcohol Consumption | % number of drinking days | 19.6 percentage of days | Standard Error 29 |
| Placebo | Self Reported Weekly Alcohol Consumption | % number of heavy drinking days | 10.0 percentage of days | Standard Error 12.6 |
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.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glycine | Self Reported Weekly Alcohol Craving | Baseline | 16.1 units on a scale | Standard Error 3.1 |
| Glycine | Self Reported Weekly Alcohol Craving | Week 12 | 10.2 units on a scale | Standard Error 3.1 |
| Placebo | Self Reported Weekly Alcohol Craving | Baseline | 17.5 units on a scale | Standard Error 3.2 |
| Placebo | Self Reported Weekly Alcohol Craving | Week 12 | 12.1 units on a scale | Standard Error 3.3 |
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.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glycine | Weekly Ratings of Negative/Positive Psychotic Symptoms | Week 12 Positive | 12.0 units on a scale | Standard Error 1.3 |
| Glycine | Weekly Ratings of Negative/Positive Psychotic Symptoms | Baseline Positive | 16.3 units on a scale | Standard Error 1.3 |
| Glycine | Weekly Ratings of Negative/Positive Psychotic Symptoms | Baseline General | 32.4 units on a scale | Standard Error 2.5 |
| Glycine | Weekly Ratings of Negative/Positive Psychotic Symptoms | Baseline Negative | 16.7 units on a scale | Standard Error 1.5 |
| Glycine | Weekly Ratings of Negative/Positive Psychotic Symptoms | Week 12 Negative | 14.9 units on a scale | Standard Error 1.5 |
| Glycine | Weekly Ratings of Negative/Positive Psychotic Symptoms | Week 12 General | 31.9 units on a scale | Standard Error 2.5 |
| Placebo | Weekly Ratings of Negative/Positive Psychotic Symptoms | Week 12 General | 29.8 units on a scale | Standard Error 2.7 |
| Placebo | Weekly Ratings of Negative/Positive Psychotic Symptoms | Week 12 Positive | 13.5 units on a scale | Standard Error 1.4 |
| Placebo | Weekly Ratings of Negative/Positive Psychotic Symptoms | Week 12 Negative | 13.0 units on a scale | Standard Error 1.6 |
| Placebo | Weekly Ratings of Negative/Positive Psychotic Symptoms | Baseline General | 29.4 units on a scale | Standard Error 2.6 |
| Placebo | Weekly Ratings of Negative/Positive Psychotic Symptoms | Baseline Positive | 15.3 units on a scale | Standard Error 1.3 |
| Placebo | Weekly Ratings of Negative/Positive Psychotic Symptoms | Baseline Negative | 12.5 units on a scale | Standard Error 1.6 |
Secondary
Baseline and End of Treatment Neurophysiological Measures
Time frame: 12 weeks
Population: Data was not collected
Secondary
Baseline and End of Treatment Quality of Life
Time frame: 12 weeks
Population: Data was not collected
Secondary
Weekly Drug Use
Time frame: 12 weeks
Population: Data was not collected