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

Systemic Lupus Erythematosus Clinical Trial

— ISLE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04276701
• Other study ID #: CHUBX 2019/38
• Status: Recruiting
• Phase: N/A
• Start date: March 10, 2021
• Est. completion date: March 2026

Study information

• Verified date: October 2023
• Source: University Hospital, Bordeaux
• Contact: Pierre DUFFAU, Prof
• Phone: (0)5 56 79 58 28
• Email: pierre.duffau[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: March 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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
• Having signed an informed consent (at the latest on the day of inclusion and before any examination required by research).

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus
• Vascular Diseases

Intervention

Biological:
• blood sample
35 ml whole blood for Peripheral blood mononuclear cell (PBMC), serum and plasma

Other:
• Ultrasonography assessment
assessment of atherosclerotic plaques and measurement of carotid intima-media thickness (cIMT)

Behavioral:
• questionnaires
Food and exercise questionnaires validated by the American heart Association

Locations

Country	Name	City	State
France	CHU de Bordeaux - service de médecine interne	Bordeaux
France	CHU de Brest - service de rhumatologie	Brest
France	CHRU de Lille - service de Médecine Interne	Lille
France	AP-HP - Hôpital Cochin - service de Médecine Interne	Paris
France	CHU de Strasbourg - service d'Immunologie Clinique	Strasbourg
Germany	Universität Freiburg	Freiburg

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Foundation for Research in Rheumatology (FOREUM)

Countries where clinical trial is conducted

France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	defined as an increase of 0.1mm or more evaluated by vascular ultrasound.	At baseline (Day 0) and 18 months from baseline
Secondary	Proportion of patients with atherosclerotic plaques		At baseline (Day 0) and 18 months from baseline
Secondary	Proportion of patients with hypertension		At baseline (Day 0) and 18 months from baseline
Secondary	Proportion of patients with Body Mass Index around 30 or more		At baseline (Day 0) and 18 months from baseline
Secondary	Proportion of patients who are smokers or past-smokers		At baseline (Day 0) and 18 months from baseline
Secondary	Proportion of patients who present a history of ischemic heart disease		At baseline (Day 0) and 18 months from baseline
Secondary	Proportion of patients who present a history of cerebral vascular accident		At baseline (Day 0) and 18 months from baseline
Secondary	Proportion of patients who present a history of peripheral artery disease		At baseline (Day 0) and 18 months from baseline
Secondary	Change in waist size in centimeters		At baseline (Day 0) and 18 months from baseline
Secondary	Change in blood glucose levels in milligram per deciliter		At baseline (Day 0) and 18 months from baseline
Secondary	Change in total cholesterol levels		At baseline (Day 0) and 18 months from baseline
Secondary	Change in HDL cholesterol levels		At baseline (Day 0) and 18 months from baseline
Secondary	Change in LDL cholesterol levels		At baseline (Day 0) and 18 months from baseline
Secondary	Change in triglycerides levels		At baseline (Day 0) and 18 months from baseline
Secondary	Change in Very Low Density Lipoprotein (VLDL) levels		At baseline (Day 0) and 18 months from baseline
Secondary	Change in C-Reactive protein levels		At baseline (Day 0) and 18 months from baseline
Secondary	Change in insulin levels		At baseline (Day 0) and 18 months from baseline
Secondary	Change in lupus disease activity according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)	score (Min value: 0 - Max value: 105), with higher values mean higher disease activity.	At baseline (Day 0) and 18 months from baseline
Secondary	Change in lupus disease activity according to Systemic Lupus International Collaborating Clinics /American College of Rheumatology (SLICC/ACR) damage index	(Min value: 0 - Max value: 47), with higher values mean more important damages.	At baseline (Day 0) and 18 months from baseline
Secondary	Change in glucocorticoids intake		At baseline (Day 0) and 18 months from baseline
Secondary	Change in platelets-derived biomarkers (P-selectin, sCD154) in micrograms per milliliter, evaluated by Western Blot analysis.		At baseline (Day 0) and 18 months from baseline
Secondary	Change in neutrophils-derived biomarkers Proteins S100A8, A9, A8/9, and A12, IL-6 in micrograms per milliliter, evaluated by Western Blot analysis.		At baseline (Day 0) and 18 months from baseline
Secondary	Change in interleukin-6 levels		At baseline (Day 0) and 18 months from baseline
Secondary	Change in interleukin-12 levels		At baseline (Day 0) and 18 months from baseline
Secondary	Change in T-Follicular Helpers lymphocytes		At baseline (Day 0) and 18 months from baseline
Secondary	Change in myeloperoxidase-conjugated DNA levels in fluorescence intensity evaluated by fluorometric assay.		At baseline (Day 0) and 18 months from baseline