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Role of Antibodies in Cognitive Dysfunction in Patients With Systemic Lupus Erythematosus

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:

  • 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 A needle is then inserted in the space between the bones in the lower back, and about 2 tablespoons of CSF is withdrawn through the needle.

Studieöversikt

Status

Avslutad

Detaljerad beskrivning

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.

Studietyp

Observationell

Inskrivning

61

Kontakter och platser

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Studieorter

    • Maryland
      • Bethesda, Maryland, Förenta staterna, 20892
        • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

  • Barn
  • Vuxen
  • Äldre vuxen

Tar emot friska volontärer

Ja

Kön som är behöriga för studier

Allt

Beskrivning

INCLUSION CRITERIA

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.

EXCLUSION CRITERIA

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 juli 2002

Avslutad studie

1 januari 2005

Studieregistreringsdatum

Först inskickad

31 juli 2002

Först inskickad som uppfyllde QC-kriterierna

31 juli 2002

Första postat (Uppskatta)

1 augusti 2002

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

4 mars 2008

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

3 mars 2008

Senast verifierad

1 januari 2005

Mer information

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

Kliniska prövningar på Systemisk lupus erythematosus

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