Libman-Sacks Endocarditis as a Cause of Neuropsychiatric Systemic Lupus Erythematosus

January 8, 2024 updated by: University of New Mexico

The purpose of this study is to determine whether Libman-Sacks endocarditis (inflammation of the heart valves) is the cause of neuropsychiatric manifestations (stroke, transient ischemic attacks, cognitive dysfunction, seizures, acute confusional state, or psychosis) in patients with systemic lupus erythematosus.

Hypothesis of the study: Libman-Sacks endocarditis (especially valve vegetations or "small valve growths") generate macro (large) and micro (tiny) emboli that occlude the medium and small cerebral vessels resulting in altered perfusion, ischemic brain injury, and major NPSLE (stroke, TIA, seizures, cognitive dysfunction, acute confusional state, or psychosis).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Specific Aim 1: To determine cross-sectionally in SLE subjects the effects of valve vegetations detected by TEE on the presence of active cerebral microemboli, altered perfusion, ischemic brain lesions, and NPSLE. Findings in SLE patients will be compared to those in controls.

Specific Aim 2: To determine longitudinally in patients with new or recurrent NPSLE and during remission whether valve vegetations, active cerebral microemboli, and abnormal cerebral perfusion improve, or normalize when compared to baseline data in patients without NPSLE or matched controls.

Specific Aim 3: To determine cross-sectionally in SLE subjects the presence of active cerebral microemboli, altered brain perfusion, brain injury, and NPSLE in relation to other valve abnormalities, such as valve thickening or valve regurgitation, in addition to or independently of valve vegetations; and to determine longitudinally these relationships in patients with NPSLE. Findings in SLE patients will be compared to baseline data in patients without NPSLE or matched controls.

Our SLE/NPSLE cohort of >400 subjects and our extensive cardiac and neuroimaging experience with TEE and MR-based techniques are essential resources for this study. We will integrate inflammatory and hemostatic parameters with multiple imaging modalities to investigate the causal connection between valve vegetations and the generation of microemboli and perfusion abnormalities, which then result in brain injury and NPSLE. A causal connection of valve vegetations to brain injury and NPSLE would result in a fundamental shift in the understanding of the pathogenesis, diagnosis, and therapy of Libman-Sacks endocarditis and NPSLE. These findings may extend to other inflammatory diseases associated with valve disease and complicated with central nervous system disease.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131-0001
        • University of New Mexico Health Sciences Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Patients with diagnosis of SLE according to the American Rheumatology Association independent of gender or ethnicity and recruited from the Rheumatology Clinics at the University of New Mexico Health Sciences Center
  • Patients (> 18 and < 60 years old) with new or recurrent major NPSLE
  • Healthy volunteers based on history and physical examination
  • Because of conscious sedation and the MR aspects of the study, women of childbearing potential who agree to participate will require to be on contraception therapy, had undergone an sterilization procedure, or have a negative pregnancy test for their inclusion in the study.

Exclusion Criteria:

  • Children (as defined by NIH) will be excluded because the neurocognitive tests are standardized for individuals 18 or older. In New Mexico, adulthood is legally defined as 18 years old. Therefore, inclusion of subjects <18 years old would invalidate the results of neurocognitive testing. Moreover, the number of children below 18 with SLE is so low in our population as to not provide a statistically viable result.
  • Subjects older than 60 years will also be excluded because their high prevalence and incidence of aging related valve and brain pathology and neurocognitive dysfunction.
  • Pregnant women will not be studied because of the need of conscious sedation during TEE and the MR aspects of the study. Women of childbearing potential who agree to participate and are not on contraception therapy or have not undergone an sterilization procedure will require a negative pregnancy test before their inclusion in the study.
  • Patients with known or suspected valve or cardiac disease unrelated to SLE such as rheumatic valve disease, active or healed infective endocarditis, congenital bicuspid aortic valves, myxomatous mitral valves with prolapse, and those with prosthetic valves and/or sustained atrial fibrillation or flutter will be excluded.
  • Patients with a known cardiac substrate for embolism (LV or LA thrombi, LV aneurysm, LV ejection fraction <40% will be excluded on enrollment, but the development of these complications during the study will be noted and considered as a separate variable.
  • Patients with non-SLE related cardiovascular or CNS disease such as congenital hypercoagulability syndromes, hypertensive encephalopathy, CNS infection, metabolic disturbances, hepatic failure, uncontrolled diabetes, or patients who are medicated with neuroleptic drugs.
  • Patients with serious medical illness unsuitable for undergoing TEE and MRI scanning.
  • Patients with thrombotic thrombocytopenic purpura (TTP).
  • Patients with contraindications to esophageal intubation (i.e. esophageal stricture or esophageal varices).
  • Patients at risk for hazard due to magnetic fields will be excluded. In critically ill patients TEE will be postponed until medically stable. Patients with supratherapeutic INR (>3.5) will not undergo TEE until INR <3.5. 11)
  • Patients without NPSLE on warfarin at the entry phase of the study.
  • History of head trauma in the form of concussion or contusion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: No intevention
No intervention
Other: Clinical and laboratory evaluations, transesophageal echocardiography, carotid duplex, transcranial duplex, and magnetic resonance of the brain
All participating subjects (patients with and without neuropsychiatric SLE and healthy controls) will undergo clinical and laboratory evaluations, transesophageal echocardiography, carotid duplex, transcranial duplex, and magnetic resonance of the brain
Other Names:
  • Clinical and laboratory and imaging tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine cross-sectionally in SLE subjects the effects of valve vegetations on the presence of active cerebral microemboli, altered perfusion, ischemic brain lesions, and NPSLE. Findings in patients will be compared to those in controls.
Time Frame: 4 years
4 years

Secondary Outcome Measures

Outcome Measure
Time Frame
To determine longitudinally in patients with new or recurrent NPSLE if during remission vegetations, cerebral microemboli, and abnormal cerebral perfusion improve, or normalize as compared to baseline data in patients without NPSLE or matched controls.
Time Frame: 4 years
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of New Mexico

Investigators

  • Principal Investigator: Carlos A Roldan, M.D., University of New Mexico

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2006

Primary Completion (Actual)

August 1, 2006

Study Completion (Actual)

August 1, 2006

Study Registration Dates

First Submitted

March 9, 2009

First Submitted That Met QC Criteria

March 9, 2009

First Posted (Estimated)

March 10, 2009

Study Record Updates

Last Update Posted (Actual)

January 10, 2024

Last Update Submitted That Met QC Criteria

January 8, 2024

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HRRC# 06-117

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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