Ignite Creation Date:
2024-05-05 @ 6:38 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00512616
Status:
WITHDRAWN
Last Update Posted:
2017-07-02
First Post:
2007-08-04
Brief Title:
A Glutamate Transporter GLT1 in the Treatment of Bipolar Disorder
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
An Investigation of the Efficacy of the Glutamate Transporter GLT 1 in the Treatment of Bipolar Depression
Status:
WITHDRAWN
Status Verified Date:
2009-09-15
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:
None
Brief Summary:
This study examines if Ceftriaxone an antibiotic will improve symptoms of depression in Bipolar Disorder
Purpose This study will examine whether the drug ceftriaxone can help patients with bipolar depression during short-term treatment of symptoms such as depressed mood psychomotor retardation slowed down thinking and movements and problems with sleep Recent studies suggest that abnormalities in the brain levels of the chemical glutamate may be involved in causing depression Ceftriaxone increases a protein in the brain called GLT1 which is responsible for regulating brain levels of glutamate
People between 18 and 65 years of age with bipolar disorder who are currently in a depressive episode of at least 4 weeks but no longer than 12 months duration may be eligible for this study
Participants are admitted to the NIH Clinical Center for about 10 weeks During the first 1 to 2 weeks they are evaluated and tapered off any antidepressant or mood stabilizers they have been taking They remain free of all medication for 2 weeks and are then randomly assigned to take either ceftriaxone or placebo for 6 weeks The study drugs are given intravenously through a vein every day To minimize discomfort patients are given a PICC line - a tube that is inserted in a vein in the arm and remains there for the duration of drug treatment This prevents the need for repeated intravenous injections
Patients have a physical examination at the beginning and at the end of the study and two electrocardiograms ECG during the study They are evaluated periodically with a series of psychiatric rating scales to determine the effects of the study drug on mood and thinking and they have periodic blood tests to assess their health status
In addition patients are asked to undergo a lumbar puncture spinal tap twice during the study to collect a sample of cerebrospinal fluid CSF the fluid that bathes the brain and spinal cord The CSF is examined to try to understand how brain chemicals are related to depression and to the effects of ceftriaxone A local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord A small amount of fluid is collected through the needle This test is optional
At the end of the study patients are offered free treatment for up to 3 months with standard medications for bipolar depression and a referral to a community physician for long-term treatment will be made
Purpose This study will examine whether the drug ceftriaxone can help patients with bipolar depression during short-term treatment of symptoms such as depressed mood psychomotor retardation slowed down thinking and movements and problems with sleep Recent studies suggest that abnormalities in the brain levels of the chemical glutamate may be involved in causing depression Ceftriaxone increases a protein in the brain called GLT1 which is responsible for regulating brain levels of glutamate
People between 18 and 65 years of age with bipolar disorder who are currently in a depressive episode of at least 4 weeks but no longer than 12 months duration may be eligible for this study
Participants are admitted to the NIH Clinical Center for about 10 weeks During the first 1 to 2 weeks they are evaluated and tapered off any antidepressant or mood stabilizers they have been taking They remain free of all medication for 2 weeks and are then randomly assigned to take either ceftriaxone or placebo for 6 weeks The study drugs are given intravenously through a vein every day To minimize discomfort patients are given a PICC line - a tube that is inserted in a vein in the arm and remains there for the duration of drug treatment This prevents the need for repeated intravenous injections
Patients have a physical examination at the beginning and at the end of the study and two electrocardiograms ECG during the study They are evaluated periodically with a series of psychiatric rating scales to determine the effects of the study drug on mood and thinking and they have periodic blood tests to assess their health status
In addition patients are asked to undergo a lumbar puncture spinal tap twice during the study to collect a sample of cerebrospinal fluid CSF the fluid that bathes the brain and spinal cord The CSF is examined to try to understand how brain chemicals are related to depression and to the effects of ceftriaxone A local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord A small amount of fluid is collected through the needle This test is optional
At the end of the study patients are offered free treatment for up to 3 months with standard medications for bipolar depression and a referral to a community physician for long-term treatment will be made
Detailed Description:
Bipolar affective disorder BPD manic-depressive illness is a common severe chronic and often life-threatening illness Increasingly it is being recognized that it is the depressive phase of the illness which contributes much of the morbidity and mortality To date only a few of the available somatic treatments have been proven to be effective for the acute phase of bipolar depression Thus there is a clear need to develop novel and improved therapeutics for bipolar depression Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system Clinical data suggests that glutamatergic modulators may have antidepressant effects in humans We first tested the glutamatergic modulator riluzole an inhibitor of glutamate release and enhancer of glutamate reuptake in astrocytes and found it to have antidepressant properties in patients with treatment-resistant major depression and bipolar depression In a recent study we found that a single intravenous dose of the non-competitive NMDA antagonist ketamine produced a rapid and relatively sustained antidepressant effect in patients with treatment-resistant major depression A recent report found that the Beta-lactam antibiotic ceftriaxone increased uptake of glutamate via increased GLT1 function Rothstein et al 2005 and had antidepressant-like effects in animal models Mineur et al 2006 Together these data suggest that the glutamatergic system may play a role in the pathophysiology and treatment of depression and that agents which more directly reduce glutamatergic neurotransmission may represent a novel class of antidepressants
We propose to expand our previous findings on the efficacy of glutamatergic modulators in patients with unipolar and bipolar depression by testing a specific new mechanism where by we use ceftriaxone to chronically increase the expression of the glutamate transporter GLT1 in order to facilitate the removal of glutamate from the synaptic cleft in an effort to reduce excessive glutamate transmission and as a result produce acute antidepressant effects The model presented here is a clinical testable one and one that if successful holds the potential to develop a group of novel pharmacological treatments for major depression
Patients ages 18 to 65 with a diagnosis of bipolar depression without psychotic features will be randomized to double-blind treatment to receive either ceftriaxone 1-4 gday or placebo intravenously for a period of 6 weeks Acute efficacy will be determined by demonstrating a greater response rate using specified criteria Approximately 86 patients with bipolar depression will be enrolled in the study
We propose to expand our previous findings on the efficacy of glutamatergic modulators in patients with unipolar and bipolar depression by testing a specific new mechanism where by we use ceftriaxone to chronically increase the expression of the glutamate transporter GLT1 in order to facilitate the removal of glutamate from the synaptic cleft in an effort to reduce excessive glutamate transmission and as a result produce acute antidepressant effects The model presented here is a clinical testable one and one that if successful holds the potential to develop a group of novel pharmacological treatments for major depression
Patients ages 18 to 65 with a diagnosis of bipolar depression without psychotic features will be randomized to double-blind treatment to receive either ceftriaxone 1-4 gday or placebo intravenously for a period of 6 weeks Acute efficacy will be determined by demonstrating a greater response rate using specified criteria Approximately 86 patients with bipolar depression will be enrolled in the study
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 |
|---|---|---|---|
| 07-M-0201 | None | None | None |