Ignite Creation Date:
2024-05-06 @ 12:09 AM
Last Modification Date:
2024-10-26 @ 10:45 AM
Study NCT ID:
NCT01503359
Status:
COMPLETED
Last Update Posted:
2016-09-16
First Post:
2011-12-30
Brief Title:
Effect of Sarcosine on Symptomatology Quality of Life Oxidative Stress and Glutamatergic Parameters in Schizophrenia
Sponsor:
Medical University of Lodz
Organization:
Medical University of Lodz
Study Overview
Official Title:
Effect of Sarcosine on Symptomatology Quality of Life Cognitive and Sexual Functioning Blood Levels of Sarcosine Glycine BDNF and MMP-9 Oculomotor Brain Metabolism and Oxidative Stress Parameters in Schizophrenia
Status:
COMPLETED
Status Verified Date:
2016-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PULSAR
Brief Summary:
The purpose of study is to determine whether dietary supplement sarcosine is effective in treatment of schizophrenia The investigators will assess impact of sarcosine on quality of life and sexual functioning In this project the investigators will also measure glycine sarcosine BDNF MMP-9 levels and oxydative stress parameters in blood brain glutamatergic metabolism parameters in magnetic resonance spectroscopy and oculomotoric changes in electrooculography
Detailed Description:
Glutamic acid is the largest excitatory neurotransmitter in the central nervous system the population of glutamatergic neurones represents approximately 50 of all neurones in the brain Being closely dependent on the inhibitory GABA system the glutamate system is responsible for the transmission and modulation of the majority of brain signals and connected with dopaminergic and serotonergic systems The glutamate system plays an important role in the pathogenesis of schizophrenia NMDA receptor antagonists including phencyclidine ketamine and MK-801 cause symptoms similar to those found in schizophrenia as well as deterioration of mental state in patients with schizophrenia What is important from a theoretical point of view NMDA agonists also cause negative symptoms which are not observed after amphetamine or other drugs intoxications Based on these observations it was assumed that normalization of glutamatergic transmission may result in an improvement in schizophrenia symptomatology
According to the assumptions of this hypothesis attempts were made to stimulate transmission within this system Due to the high risk of excitotoxic effects induction therapy with glutamic acid is not administered hyperactivity of glutamatergic system leading to nerve cell damage was observed in neurodegenerative diseases Along with glutamic acid and voltage changes dependent on another glutamatergic receptor - AMPA presence of glycine is necessary to stimulate the NMDA receptor This widely distributed amino acid an important element of protein chains is present in a daily diet average consumption amounts to 2gday In addition to building properties it is of paramount importance in the central nervous system As a primary transmitter in glycinergic neurones it belongs to the class I of neurotransmitters Moreover it also plays a role as a co-agonist and a modulator for example in the glutamatergic system Glutamic acid is released from nerve endings into the synaptic cleft where it is re-uptaken and dispersed which in consequence results in a rapid decline in its concentration in the vicinity of NMDA receptors As a result the time of receptor binding is short Intrasynaptic glycine turnover is different - it resides inside the synapses permanently depending on the concentration and to a greater or lesser extent binds to a modulatory site Glial cells with identified glycine transport system GlyT-1 are responsible for maintaining a stable level of glycine in neuronal junctions New research on inhibitors of this transport system GTI eg sarcosine which may have similar or better effects to glycine administration have begun Glycine does not bind to all the modulatory sites on NMDA receptor in vivo and augmentation of this saturation intensifies glutamatergic transmission This phenomenon is particularly observed in individuals with relatively low not sufficient for maximum saturation of the receptor site levels of synaptic glycine
We hypothesize that supplementation of sarcosine helps achieve betterment in symptomatology general quality of life and also cognitive functioning and other prefrontal derivatives eg oculomotor functions
To extend research we planned assessing blood levels of glycine sarcosine but also other parameters involved in glutamatergic transmission such as BDNF and metalproteinase MMP-9 Knowing excitotoxic properties of glutamate TBARS thiobarbituric acid reactive substances - oxidative stress related will be assessed
Methodology of the study We plan to enroll 60-70 patients in stable mental state meeting criteria for schizophrenia according to ICD-10 with predominant negative symptoms minimum of 21 points and severity of each negative symptom at least 3 points in PANSS-Negative subscale
Main study part will be continued for 26 weeks T0-T26 and 10 visits W1-W10 The preceding 12-week period W0-W1 will be used for evaluation of stability of mental state and pharmacotherapy
Patients on visit T0 will be randomized to two comparable groups of 30 patients sarcosine and control group Researchers and patients will not have information on the administered treatment
During the study patients will receive previous antipsychotic treatment at least 3-month without dosage change Mental stability will be assessed during the preceding period W1 and W0 visit - 12 weeks before W1 Sarcosine or placebo will be augmented between visits W1 and W9 the subsequent period between W9 and W10 will be used to evaluate the consequences of withdrawal sarcosine and placebo
Information on the history of the disease and current mental status will be obtained during the psychiatric examination in part standardized by the use of commonly accepted psychiatric scales PANSS Calgary Depression Scale CGI SAS and quality of life and sexual activity scales Assessment of the use of psychiatric scales will be used on each of the visits
As the basic tools used to study cognitive functioning test Wisconsin Card Sorting WCST Trail Making Test TMT and Stroop Test will be used Psychological testing will be performed by a psychologist on visits W1 W6 and W9
Assessment of metabolism of glycine and glutamic acid in brain tissue in the frontal cortex and hippocampus using magnetic resonance spectroscopy electrooculography parameter of oxidative stress - T-BARS and blood assessments glycine sarcosine BDNF and MMP-9 will be performed on visits W1 and W9
According to the assumptions of this hypothesis attempts were made to stimulate transmission within this system Due to the high risk of excitotoxic effects induction therapy with glutamic acid is not administered hyperactivity of glutamatergic system leading to nerve cell damage was observed in neurodegenerative diseases Along with glutamic acid and voltage changes dependent on another glutamatergic receptor - AMPA presence of glycine is necessary to stimulate the NMDA receptor This widely distributed amino acid an important element of protein chains is present in a daily diet average consumption amounts to 2gday In addition to building properties it is of paramount importance in the central nervous system As a primary transmitter in glycinergic neurones it belongs to the class I of neurotransmitters Moreover it also plays a role as a co-agonist and a modulator for example in the glutamatergic system Glutamic acid is released from nerve endings into the synaptic cleft where it is re-uptaken and dispersed which in consequence results in a rapid decline in its concentration in the vicinity of NMDA receptors As a result the time of receptor binding is short Intrasynaptic glycine turnover is different - it resides inside the synapses permanently depending on the concentration and to a greater or lesser extent binds to a modulatory site Glial cells with identified glycine transport system GlyT-1 are responsible for maintaining a stable level of glycine in neuronal junctions New research on inhibitors of this transport system GTI eg sarcosine which may have similar or better effects to glycine administration have begun Glycine does not bind to all the modulatory sites on NMDA receptor in vivo and augmentation of this saturation intensifies glutamatergic transmission This phenomenon is particularly observed in individuals with relatively low not sufficient for maximum saturation of the receptor site levels of synaptic glycine
We hypothesize that supplementation of sarcosine helps achieve betterment in symptomatology general quality of life and also cognitive functioning and other prefrontal derivatives eg oculomotor functions
To extend research we planned assessing blood levels of glycine sarcosine but also other parameters involved in glutamatergic transmission such as BDNF and metalproteinase MMP-9 Knowing excitotoxic properties of glutamate TBARS thiobarbituric acid reactive substances - oxidative stress related will be assessed
Methodology of the study We plan to enroll 60-70 patients in stable mental state meeting criteria for schizophrenia according to ICD-10 with predominant negative symptoms minimum of 21 points and severity of each negative symptom at least 3 points in PANSS-Negative subscale
Main study part will be continued for 26 weeks T0-T26 and 10 visits W1-W10 The preceding 12-week period W0-W1 will be used for evaluation of stability of mental state and pharmacotherapy
Patients on visit T0 will be randomized to two comparable groups of 30 patients sarcosine and control group Researchers and patients will not have information on the administered treatment
During the study patients will receive previous antipsychotic treatment at least 3-month without dosage change Mental stability will be assessed during the preceding period W1 and W0 visit - 12 weeks before W1 Sarcosine or placebo will be augmented between visits W1 and W9 the subsequent period between W9 and W10 will be used to evaluate the consequences of withdrawal sarcosine and placebo
Information on the history of the disease and current mental status will be obtained during the psychiatric examination in part standardized by the use of commonly accepted psychiatric scales PANSS Calgary Depression Scale CGI SAS and quality of life and sexual activity scales Assessment of the use of psychiatric scales will be used on each of the visits
As the basic tools used to study cognitive functioning test Wisconsin Card Sorting WCST Trail Making Test TMT and Stroop Test will be used Psychological testing will be performed by a psychologist on visits W1 W6 and W9
Assessment of metabolism of glycine and glutamic acid in brain tissue in the frontal cortex and hippocampus using magnetic resonance spectroscopy electrooculography parameter of oxidative stress - T-BARS and blood assessments glycine sarcosine BDNF and MMP-9 will be performed on visits W1 and W9
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| N N402 268836 | OTHER_GRANT | Ministry of Science and Higher Education Poland | None |