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

NCT ID: NCT04276701

Last Updated: 2024-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-10

Study Completion Date

2027-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Systemic Lupus Erythematosus

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Systemic lupus erythematosus (SLE)

Group Type EXPERIMENTAL

blood sample

Intervention Type BIOLOGICAL

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

Ultrasonography assessment

Intervention Type OTHER

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

questionnaires

Intervention Type BEHAVIORAL

Food and exercise questionnaires validated by the American heart Association

Interventions

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blood sample

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

Intervention Type BIOLOGICAL

Ultrasonography assessment

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

Intervention Type OTHER

questionnaires

Food and exercise questionnaires validated by the American heart Association

Intervention Type BEHAVIORAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Foundation for Research in Rheumatology (FOREUM)

UNKNOWN

Sponsor Role collaborator

University Hospital, Bordeaux

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pierre DUFFAU, Prof

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Patrick BLANCO, Prof

Role: STUDY_DIRECTOR

University Hospital, Bordeaux

Locations

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CHU de Bordeaux - service de médecine interne

Bordeaux, , France

Site Status RECRUITING

CHU de Brest - service de rhumatologie

Brest, , France

Site Status RECRUITING

CHRU de Lille - service de Médecine Interne

Lille, , France

Site Status RECRUITING

AP-HP - Hôpital Cochin - service de Médecine Interne

Paris, , France

Site Status NOT_YET_RECRUITING

CHU de Strasbourg - service d'Immunologie Clinique

Strasbourg, , France

Site Status RECRUITING

Universität Freiburg

Freiburg im Breisgau, , Germany

Site Status NOT_YET_RECRUITING

Countries

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France Germany

Central Contacts

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Pierre DUFFAU, Prof

Role: CONTACT

(0)5 56 79 58 28 ext. +33

Thomas BARNETCHE, MD

Role: CONTACT

(0)5.57.82.04.93 ext. +33

Facility Contacts

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Pierre DUFFAU, Prof

Role: primary

(0)5 56 79 58 28 ext. +33

Thomas BARNETCHE, PhD

Role: backup

(0)5 57 82 04 93 ext. +33

Sandrine JOUSSE-JOULIN, Prof

Role: primary

Eric HACHULLA, Prof

Role: primary

Nathalie COSTEDOAT-CHALUMEAU, Prof

Role: primary

Thierry MARTIN, Prof

Role: primary

(0)3 69 55 03 85 ext. +33

Reinhard E Voll, Prof

Role: primary

Other Identifiers

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CHUBX 2019/38

Identifier Type: -

Identifier Source: org_study_id

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