Immune Mediators and Metabolites to Stratify Systemic Lupus Erythematosus Patients at High Risk of Cardio Vascular Diseases

NCT04276701 | Active Not Recruiting

• 1 other identifier: CHUBX 2019/38
• Study Type: interventional
• Target: 500
• Locations: 2 countries
• Sites: 6

Brief Summary

Accelerated atherosclerosis is an established complication of systemic autoimmune diseases, particularly SLE. Young female patients with SLE are more likely to develop myocardial infarction than matched healthy controls, and CVD is nowadays one of the most common causes of death (27%) in lupus patients. While traditional CV risk factors cannot explain such increased CV morbidity associated with SLE, common disease factors shared between SLE, atherosclerosis and treatment exposure may be of outmost importance in this process. Our group made 3 findings of particular interest that could link SLE pathogenesis and atherosclerosis-associated immune dysregulation: 1/ the investigators identified specific immunometabolites (circulating nucleotide-derived metabolites adenine and N4-acetylcytidine), which are increased in the circulation of SLE patients. These immunometabolites trigger a constitutive inflammasome activation resulting in aberrant IL1-β production. Given that IL1-β inhibition was reported to significantly reduce CV events without altering lipid levels, the investigators propose that these immunometabolites may represent novel candidate biomarkers of CV risk stratification in SLE. 2/ the investigators identified OX40L as an important costimulatory molecule implicated in follicular helper T cell (Tfh) activation in SLE. Interestingly, OX40L polymorphism has been associated to both SLE and atherosclerosis, and Tfh have been recently shown to accelerate atherosclerosis progression. 3/ Immune complexes-activated platelets sustain aberrant immune response in SLE and block immunosuppressive functions of regulatory T cells (Tregs) in a P-selectin/PSGL1 dependent manner. Selectins and Tregs cell dysfunction are well accepted players in atherosclerosis pathogenesis. Thus there are multiple pathways that are shared between SLE and atherosclerosis and that may results in an increased risk of CV-associated morbidity in SLE patients. Exploring these interconnected pathways in SLE patients together with traditional and other well-established disease-related factors, might lead to a better stratification of CV risk in SLE. The aim of this study is to investigate the accuracy, predictive value and utility of immunological disease-related biomarkers in stratifying CV risk in patients with SLE.

Conditions

Systemic Lupus Erythematosus

Keywords

Immune mediators; Immune metabolites; cardio vascular diseases; Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who show atherosclerotic plaque progression defined by the absence of carotid plaque in patients at baseline and its subsequent development at follow-up evaluated by semi-automated 3D vascular ultrasound

  At baseline (Day 0) and 18 months from baseline

Secondary Outcomes (26)

• Proportion of patients who show carotid Intima Media Thickness (cIMT) progression measured in the common carotid artery, at the bulb and the origin of the internal carotid artery

  At baseline (Day 0) and 18 months from baseline

• Proportion of patients with atherosclerotic plaques

  At baseline (Day 0) and 18 months from baseline

• Proportion of patients with hypertension

  At baseline (Day 0) and 18 months from baseline

• Proportion of patients with Body Mass Index around 30 or more

  At baseline (Day 0) and 18 months from baseline

• Proportion of patients who are smokers or past-smokers

  At baseline (Day 0) and 18 months from baseline

Study Arms (1)

Systemic lupus erythematosus (SLE)

EXPERIMENTAL

Biological: blood sample; Other: Ultrasonography assessment; Behavioral: questionnaires

Interventions

blood sample BIOLOGICAL

35 ml whole blood for Peripheral blood mononuclear cell (PBMC), serum and plasma

Systemic lupus erythematosus (SLE)

Ultrasonography assessment OTHER

assessment of atherosclerotic plaques and measurement of carotid intima-media thickness (cIMT)

Systemic lupus erythematosus (SLE)

questionnaires BEHAVIORAL

Food and exercise questionnaires validated by the American heart Association

Systemic lupus erythematosus (SLE)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patient aged over 18 years old.
• SLE diagnosis according to the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus

You may not qualify if:

• Pregnancy or breast-feeding for woman.
• Person concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Foundation for Research in Rheumatology (FOREUM): collaborator

Study Sites (6)

CHU de Bordeaux - service de médecine interne

Bordeaux, France

Location

CHU de Brest - service de rhumatologie

Brest, France

Location

CHRU de Lille - service de Médecine Interne

Lille, France

Location

AP-HP - Hôpital Cochin - service de Médecine Interne

Paris, France

Location

CHU de Strasbourg - service d'Immunologie Clinique

Strasbourg, France

Location

Universität Freiburg

Freiburg im Breisgau, Germany

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Blood Specimen Collection; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Pierre DUFFAU, Prof

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Patrick BLANCO, Prof

  University Hospital, Bordeaux

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2020
• First Posted: February 19, 2020
• Study Start: March 10, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); FR (5)