Ignite Creation Date:
2024-05-05 @ 11:27 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00042523
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2002-07-31
Brief Title:
Role of Antibodies in Cognitive Dysfunction in Patients With Systemic Lupus Erythematosus
Sponsor:
National Institute of Arthritis and Musculoskeletal and Skin Diseases NIAMS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Role of the Antibody Against NR2 Glutamate Receptor in Cognitive Dysfunction in Patients With Systemic Lupus Erythematosus
Status:
COMPLETED
Status Verified Date:
2005-01
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 will examine the possible relationship between certain antibodies found in patients with systemic lupus erythematosus SLE and cognitive thought processing impairment in these patients Antibodies are proteins produced by cells of the immune system to fight foreign invaders such as bacteria and viruses In autoimmune diseases like SLE however the immune system produces antibodies against the bodys own healthy tissues Antibodies targeting the brain may cause cognitive dysfunction Many patients with SLE have mild to severe cognitive impairment involving for example short- or long-term memory thought processing and relating objects in time and space
Patients 18 years of age and older with SLE may be eligible for this study Participants will undergo the following tests and procedures
Medical history and physical examination including blood and urine tests
Psychiatric interview and questionnaire to assess depression
Neuropsychological tests - answering questions given by an examiner or filling out a test form or questionnaire
Tests of cognitive function - answering questions given by an automated computer program or performing tasks using a computer mouse
Magnetic resonance imaging MRI of the brain - a test that uses strong magnetic fields and radio waves to generate images of the brain The patient lies still on a stretcher inside a cylinder containing a magnetic field The patients head is stabilized with a plastic strap and foam pads During the imaging a substance called gadolinium-DTPA is injected into an arm vein through a catheter thin plastic tube This substance is used to enhance the images
Patients may also be asked to undergo an optional procedure called a lumbar puncture spinal tap to examine the relationship between cognitive impairment and the amount of antibodies in the cerebrospinal fluid CSF- fluid that circulates around the brain and spinal cord For this procedure a small area of skin on the lower back is numbed with a local anesthetic A needle is then inserted in the space between the bones in the lower back and about 2 tablespoons of CSF is withdrawn through the needle
Patients 18 years of age and older with SLE may be eligible for this study Participants will undergo the following tests and procedures
Medical history and physical examination including blood and urine tests
Psychiatric interview and questionnaire to assess depression
Neuropsychological tests - answering questions given by an examiner or filling out a test form or questionnaire
Tests of cognitive function - answering questions given by an automated computer program or performing tasks using a computer mouse
Magnetic resonance imaging MRI of the brain - a test that uses strong magnetic fields and radio waves to generate images of the brain The patient lies still on a stretcher inside a cylinder containing a magnetic field The patients head is stabilized with a plastic strap and foam pads During the imaging a substance called gadolinium-DTPA is injected into an arm vein through a catheter thin plastic tube This substance is used to enhance the images
Patients may also be asked to undergo an optional procedure called a lumbar puncture spinal tap to examine the relationship between cognitive impairment and the amount of antibodies in the cerebrospinal fluid CSF- fluid that circulates around the brain and spinal cord For this procedure a small area of skin on the lower back is numbed with a local anesthetic A needle is then inserted in the space between the bones in the lower back and about 2 tablespoons of CSF is withdrawn through the needle
Detailed Description:
Cognitive dysfunction is common in patients with systemic lupus erythematosus SLE observed in as many as two-thirds of patients Cognitive dysfunction of long duration or with deterioration can have a significant impact on occupational functioning of SLE patients and also compromise compliance to treatment
The pathogenesis of cognitive dysfunction in SLE patients is likely multifactorial including vascular origin direct neuronal damage due to autoantibodies or cytokines metabolic effects or effects of certain medications More than one half of SLE patients have anti-DNA antibodies and it was recently demonstrated that a subset of anti-DNA antibodies cross-reacts with a pentapeptide consensus sequence residues 283-287 of the human N-methyl-D-aspartate NMDA receptor NR2a and NR2b subunits and can cause excitotoxic death of neurons NMDA receptors are important in memory function and learning and thus such antibodies may mediate cognitive dysfunction in SLE
In this cross-sectional study up to 60 patients with SLE may be enrolled Participants will undergo neuropsychological testing neuroimaging studies and blood tests for antibody with the reactivity to the pentapeptide consensus sequence of the human NMDA receptor NR2a and NR2b subunits anti-pentapeptide Ab
The primary objective of this study is to evaluate the association between cognitive dysfunction and serum anti-pentapeptide Ab Magnetic resonance imaging MRI will be performed for evaluation of potentially confounding central nervous system CNS disease such as cerebral infarction and of blood brain barrier breakdown by employing gadolinium enhancement Furthermore in participants who agree a lumbar puncture will be performed and cerebrospinal fluid will be obtained for preliminary evaluation of the intrathecal levels of the anti-pentapeptide Ab associated with cognitive dysfunction
If the anti-pentapeptide Ab is associated with cognitive dysfunction therapeutic interventions via NR2 receptor blockade or the blockade of the anti-pentapeptide Ab may be considered in a future study
The pathogenesis of cognitive dysfunction in SLE patients is likely multifactorial including vascular origin direct neuronal damage due to autoantibodies or cytokines metabolic effects or effects of certain medications More than one half of SLE patients have anti-DNA antibodies and it was recently demonstrated that a subset of anti-DNA antibodies cross-reacts with a pentapeptide consensus sequence residues 283-287 of the human N-methyl-D-aspartate NMDA receptor NR2a and NR2b subunits and can cause excitotoxic death of neurons NMDA receptors are important in memory function and learning and thus such antibodies may mediate cognitive dysfunction in SLE
In this cross-sectional study up to 60 patients with SLE may be enrolled Participants will undergo neuropsychological testing neuroimaging studies and blood tests for antibody with the reactivity to the pentapeptide consensus sequence of the human NMDA receptor NR2a and NR2b subunits anti-pentapeptide Ab
The primary objective of this study is to evaluate the association between cognitive dysfunction and serum anti-pentapeptide Ab Magnetic resonance imaging MRI will be performed for evaluation of potentially confounding central nervous system CNS disease such as cerebral infarction and of blood brain barrier breakdown by employing gadolinium enhancement Furthermore in participants who agree a lumbar puncture will be performed and cerebrospinal fluid will be obtained for preliminary evaluation of the intrathecal levels of the anti-pentapeptide Ab associated with cognitive dysfunction
If the anti-pentapeptide Ab is associated with cognitive dysfunction therapeutic interventions via NR2 receptor blockade or the blockade of the anti-pentapeptide Ab may be considered in a future 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 |
|---|---|---|---|
| 02-AR-0267 | None | None | None |