Systemic Lupus ErythematosusNCT00042523
Role of Antibodies in Cognitive Dysfunction in Patients With Systemic Lupus Erythematosus
An observational study of Systemic Lupus Erythematosus, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Systemic Lupus Erythematosus
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2002to Jan 2005
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 18 years of age or greater.
- Must be willing and able to provide informed consent.
- Have fulfilled the 1997 updated American College of Rheumatology (ACR) criteria for SLE.
Who cannot join
- History of neurologic diseases including head injury resulting in loss of consciousness, strokes, seizures, toxic exposure.
- History of clinically documented transient ischemic attacks within 6 months of screening visit.
- Currently taking anticonvulsant agents
- Limited familiarity with English that, in the opinion of the investigator, would limit participants' performance on neuropsychological tests.
- Any clinically significant medical condition that, in the opinion of the investigator, would pose added risk for study participants.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Bethesda, Maryland, 20892
About this study
Official title: Role of the Antibody Against NR2 Glutamate Receptor in Cognitive Dysfunction in Patients With Systemic Lupus Erythematosus
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 body's 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:
Read more
- 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 patient's 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.
Read the 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.
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Autoantibody, Anti-DNA Antibody, Cross-Reactivity, Neuron Loss, Imaging, Lupus, SLE, Systemic Lupus Erythematosus
- Medical subject headings
- Lupus Erythematosus, Systemic
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2002 (estimated)
- Study startJul 2002
- Study completionJan 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 61 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00042523
- Sponsor's protocol ID
- 020267
- Other IDs
- 02-AR-0267
- Status last verified
- Jan 2005
- First submitted
- 31 Jul 2002
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Hochberg MC. Systemic lupus erythematosus. Rheum Dis Clin North Am. 1990 Aug;16(3):617-39.
PubMed 2217961Mills JA. Systemic lupus erythematosus. N Engl J Med. 1994 Jun 30;330(26):1871-9. doi: 10.1056/NEJM199406303302608. No abstract available.
PubMed 8196732Denburg SD, Denburg JA, Carbotte RM, Fisk JD, Hanly JG. Cognitive deficits in systemic lupus erythematosus. Rheum Dis Clin North Am. 1993 Nov;19(4):815-31.
PubMed 8265824
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of the Antibody Against NR2 Glutamate Receptor in Cognitive Dysfunction in Patients With Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT00042523
- Acronym / sponsor ID
- 020267
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Autoantibody, Anti-DNA Antibody, Cross-Reactivity, Neuron Loss, Imaging, Lupus, SLE, Systemic Lupus Erythematosus
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 61 participants
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)US National Institutes of Health
- Study start
- Jul 2002
- Study completion
- Jan 2005
- First posted
- 1 Aug 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 body's 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 patient's 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.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 18 years of age or greater.
- Must be willing and able to provide informed consent.
- Have fulfilled the 1997 updated American College of Rheumatology (ACR) criteria for SLE.
Key exclusion criteria (5 listed)
- History of neurologic diseases including head injury resulting in loss of consciousness, strokes, seizures, toxic exposure.
- History of clinically documented transient ischemic attacks within 6 months of screening visit.
- Currently taking anticonvulsant agents
- Limited familiarity with English that, in the opinion of the investigator, would limit participants' performance on neuropsychological tests.
- Any clinically significant medical condition that, in the opinion of the investigator, would pose added risk for study participants.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 2217961Hochberg MC. Systemic lupus erythematosus. Rheum Dis Clin North Am. 1990 Aug;16(3):617-39.
- Background: PubMed 8196732Mills JA. Systemic lupus erythematosus. N Engl J Med. 1994 Jun 30;330(26):1871-9. doi: 10.1056/NEJM199406303302608. No abstract available.
- Background: PubMed 8265824Denburg SD, Denburg JA, Carbotte RM, Fisk JD, Hanly JG. Cognitive deficits in systemic lupus erythematosus. Rheum Dis Clin North Am. 1993 Nov;19(4):815-31.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Systemic Lupus Erythematosus, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00042523, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.