Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000372
Status:
WITHDRAWN
Last Update Posted:
2014-06-12
First Post:
1999-11-02
Brief Title:
Glycine and D-Cycloserine in Schizophrenia
Sponsor:
Massachusetts General Hospital
Organization:
Massachusetts General Hospital
Study Overview
Official Title:
A Placebo Controlled Trial of Glycine Added to Clozapine in Schizophrenia
Status:
WITHDRAWN
Status Verified Date:
2014-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Pairing D-Cycloserine with Clozapine was found to worsen negative side effects in patients with Schizophrenia so the study was suspended
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to compare the effects of D-cycloserine and glycine for treating negative symptoms such as loss of interest loss of energy loss of warmth and loss of humor which occur between phases of positive symptoms marked by hallucinations delusions and thought confusions in schizophrenics
Clozapine is currently the most effective treatment for negative symptoms of schizophrenia Two other drugs D-cycloserine and glycine are being investigated as new treatments D-cycloserine improves negative symptoms when added to some drugs but may worsen these symptoms when given with clozapine Glycine also improves negative symptoms and may still be able to improve these symptoms when given with clozapine This study gives either D-cycloserine or glycine or an inactive placebo with clozapine to determine which is the best combination
Patients will be assigned to 1 of 3 groups Group 1 will receive D-cycloserine plus clozapine Group 2 will receive glycine plus clozapine Group 3 will receive an inactive placebo plus clozapine Patients will receive these medications for 8 weeks Negative symptoms of schizophrenia will be monitored through the Scale for the Assessment of Negative Symptoms Positive symptoms will be monitored through the Positive and Negative Syndrome Scale and additionally subjects will complete the Brief Psychiatric Rating Scale and the Global Assessment Scale
An individual may be eligible for this study if heshe is 18 to 65 years old and has been diagnosed with schizophrenia
Clozapine is currently the most effective treatment for negative symptoms of schizophrenia Two other drugs D-cycloserine and glycine are being investigated as new treatments D-cycloserine improves negative symptoms when added to some drugs but may worsen these symptoms when given with clozapine Glycine also improves negative symptoms and may still be able to improve these symptoms when given with clozapine This study gives either D-cycloserine or glycine or an inactive placebo with clozapine to determine which is the best combination
Patients will be assigned to 1 of 3 groups Group 1 will receive D-cycloserine plus clozapine Group 2 will receive glycine plus clozapine Group 3 will receive an inactive placebo plus clozapine Patients will receive these medications for 8 weeks Negative symptoms of schizophrenia will be monitored through the Scale for the Assessment of Negative Symptoms Positive symptoms will be monitored through the Positive and Negative Syndrome Scale and additionally subjects will complete the Brief Psychiatric Rating Scale and the Global Assessment Scale
An individual may be eligible for this study if heshe is 18 to 65 years old and has been diagnosed with schizophrenia
Detailed Description:
To determine if glycine produces improvement in negative symptoms and D-cycloserine produces worsening in symptoms compared to placebo patients will undergo a double blind study of d-cycloserine and glycine treatment added to clozapine
Clozapine is more effective for negative symptoms of schizophrenia than conventional neuroleptics but the neurochemical actions contributing to this superior clinical efficacy remain unclear Recent evidence points to a role for glutamatergic dysregulation in schizophrenia as well as important differences between conventional agents and clozapine in effects upon glutamatergic systems D-cycloserine a partial agonist at the glycine modulatory site of the N-methyl-D-aspartate NMDA receptor improves negative symptoms when added to conventional agents and worsens negative symptoms when added to clozapine High-dose glycine also improves negative symptoms and has provided preliminary evidence suggesting that glycine improves negative symptoms when added to clozapine Serum concentrations of glycine predicted response to both high-dose glycine and D-cycloserine Both clozapine and D-cycloserine may improve negative symptoms by activation of the glycine modulatory site of the NMDA receptor complex Because D-cycloserine is a partial agonist it may act as an antagonist at the glycine site in the presence of clozapine whereas the full agonist glycine would not be expected to worsen negative symptoms in the presence of clozapine
This study proposes to administer a fixed-dose of D-cycloserine glycine or placebo added to clozapine in 45 patients with schizophrenia Because assessments are standardized between studies results from this study can be compared with results from a previous study of D-cycloserine added to conventional neuroleptic
The study was ultimately suspended before participants were enrolled due to definitive findings indicating that pairing treatment of D-cycloserine with Clozapine resulted in worsening of negative symptoms
Clozapine is more effective for negative symptoms of schizophrenia than conventional neuroleptics but the neurochemical actions contributing to this superior clinical efficacy remain unclear Recent evidence points to a role for glutamatergic dysregulation in schizophrenia as well as important differences between conventional agents and clozapine in effects upon glutamatergic systems D-cycloserine a partial agonist at the glycine modulatory site of the N-methyl-D-aspartate NMDA receptor improves negative symptoms when added to conventional agents and worsens negative symptoms when added to clozapine High-dose glycine also improves negative symptoms and has provided preliminary evidence suggesting that glycine improves negative symptoms when added to clozapine Serum concentrations of glycine predicted response to both high-dose glycine and D-cycloserine Both clozapine and D-cycloserine may improve negative symptoms by activation of the glycine modulatory site of the NMDA receptor complex Because D-cycloserine is a partial agonist it may act as an antagonist at the glycine site in the presence of clozapine whereas the full agonist glycine would not be expected to worsen negative symptoms in the presence of clozapine
This study proposes to administer a fixed-dose of D-cycloserine glycine or placebo added to clozapine in 45 patients with schizophrenia Because assessments are standardized between studies results from this study can be compared with results from a previous study of D-cycloserine added to conventional neuroleptic
The study was ultimately suspended before participants were enrolled due to definitive findings indicating that pairing treatment of D-cycloserine with Clozapine resulted in worsening of negative symptoms
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 |
|---|---|---|---|
| DSIR | None | None | None |