- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00338598
Facilitation of NMDA Receptor Function in Patients With Schizophrenia and Co-morbid Alcoholism
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Connecticut
-
West Haven, Connecticut, United States, 06516
- VA Connecticut Healthcare System
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Glycine
Glycine, 0.8 gr per kg given in two daily doses
|
Glycine, 0.8 gr per kg given in two daily doses
|
Placebo Comparator: placebo
placebo will be administered.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Self Reported Weekly Alcohol Consumption
Time Frame: 12 weeks
|
Percentage of drinking days and heavy drinking days using timeline follow back
|
12 weeks
|
Self Reported Weekly Alcohol Craving
Time Frame: 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.
|
12 weeks
|
Weekly Ratings of Negative/Positive Psychotic Symptoms
Time Frame: 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.
|
12 weeks
|
Baseline and End of Treatment Cognitive Functioning Measures (Hopkins)
Time Frame: 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.
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Weekly Drug Use
Time Frame: 12 weeks
|
12 weeks
|
Baseline and End of Treatment Quality of Life
Time Frame: 12 weeks
|
12 weeks
|
Baseline and End of Treatment Neurophysiological Measures
Time Frame: 12 weeks
|
12 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Ismene Petrakis, M.D., Yale University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Alcohol-Related Disorders
- Substance-Related Disorders
- Schizophrenia Spectrum and Other Psychotic Disorders
- Alcoholism
- Schizophrenia
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Glycine Agents
- Glycine
Other Study ID Numbers
- 20915
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Alcoholism
-
Yale UniversityCompletedFamilial Alcoholism VulnerabilityUnited States
-
Yonsei UniversityTerminated
-
Yale UniversityNational Institute on Alcohol Abuse and Alcoholism (NIAAA)RecruitingFamilial Alcoholism VulnerabilityUnited States
-
University of Southern DenmarkActive, not recruitingGeneral Practice | Alcohol Abuse Alcoholism | Screening and Brief InterventionDenmark
-
University of FloridaNational Institute on Alcohol Abuse and Alcoholism (NIAAA)CompletedEffects of Family History of Alcoholism and Sex on Alcohol AnalgesiaUnited States
-
Brown UniversityNational Institute on Alcohol Abuse and Alcoholism (NIAAA)CompletedAlcoholic Liver Disease | Alcoholism,United States
-
Khoo Teck Puat HospitalNot yet recruitingEmergencies | Alcohol Use Disorder | Alcoholism and Alcohol Abuse
-
National Institute on Drug Abuse (NIDA)The Peter G. Dodge Foundation (PGDF)Completed
-
Virginia Commonwealth UniversityNational Institute on Alcohol Abuse and Alcoholism (NIAAA); Yale University; University...CompletedAlcoholismUnited States
-
University of Sao PauloCoordenação de Aperfeiçoamento de Pessoal de Nível Superior.; Conselho Nacional... and other collaboratorsEnrolling by invitation
Clinical Trials on placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States