Antiphospholipid Syndrome (APS) Clinical Trial
Official title:
Efficiency of Hydroxychloroquine on the Endothelial Dysfunction in Antiphospholipid Syndrome (APLAQUINE)
This study evaluates the benefits of hydroxychloroquine on arterial function in
antiphospholipid syndrome.
Briefly, the patients will be randomized in two groups, one will receive hydroxychloroquine
and standard treatment, the other will receive placebo in addition of standard treatment.
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent
thrombotic events and miscarriages, with persistently positive antiphospholipid antibodies
(aPL). APS may be isolated (primary APS) or associated to a connective tissue disease, most
often systemic lupus erythematous (SLE).
Pathogenic effects of aPL were first described by the demonstration that in vitro incubation
of endothelial cells or monocytes with aPL induce an endothelial dysfunction characterized
by pro-coagulant (overexpression of tissue factor and modulation of protein C and S),
pro-inflammatory (increased level of IL-6(interleukin 6) , IL-1β and TNFα) and pro-adhesive
(increased levels of ICAM-1(intercellular adhesion molecule ), VCAM-1 (vascular endothelial
cell adhesion molecule) and E-selectin) phenotypes. In parallel the investigators and others
reported that endothelial function, assessed by flow mediated dilatation, is altered in
patients with primary and secondary forms of APS. Although a role for TLR (toll-like
receptor )-mediated NFkB translocation has been advanced, the pathogenic mechanisms that
lead to in vivo endothelial injury in APS are incompletely understood.
In an experimental model, the investigators demonstrated that passive transfer of human aPL
to mice induced a marked endothelial dysfunction assessed ex vivo in small resistance
arteries, and an increase in TNFα levels. Moreover, the investigators group have
demonstrated that patients with primary arterial APS display endothelial dysfunction and
structural arterial changes, associated with a pro-oxidative and pro-coagulant state and
with activation of the TLR2 and TLR4 signalling pathways.
Recently, in a preliminary study the investigators have found that endothelial glycocalyx
which is an important part of the vascular barrier and which is intimately linked to the
homeostatic functions of the endothelium was altered in APL patients.
Hydroxychloroquine (HCQ) is an antimalarial drug, also used to treat rheumatic diseases such
as SLE. There is experimental evidence to suggest a direct role of hydroxychloroquine on the
pathophysiology of APS: it directly reduces the binding of antibodies on the phospholipid
bilayers, protects the annexin A5 anticoagulant shield and it reverses platelet adhesion
induced by aPL.
Furthermore it is known to decrease the expression of lysosomal TLRs, but also extra
lysosomal TLR2 and TLR4.
The aim of this study is to investigate whether treatment with hydroxychloroquine modulates
vascular endothelial function in patients.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Not yet recruiting |
NCT06371417 -
Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)
|
Phase 1 | |
| Recruiting |
NCT06315530 -
Effect of Telitacicept on Antibody Titers in Primary APS Patients
|
Phase 2 | |
| Active, not recruiting |
NCT01787305 -
Pilot Study of Gut Commensals in Antiphospholipid Syndrome
|