Clinical Trial: Study of the Efficiency of Hydroxychloroquine on the Endothelial Dysfunction and Its Vascular Consequences During the Antiphospholipid Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Efficiency of Hydroxychloroquine on the Endothelial Dysfunction in Antiphospholipid Syndrome (APLAQUINE)

Brief Summary:

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.


Detailed Summary:

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 impo
Sponsor: University Hospital, Rouen

Current Primary Outcome: Change from baseline flow mediated dilatation of brachial artery [ Time Frame: 6 months ]

The brachial artery diameter and blood flow are measured by echotracking and Doppler before and just after and ischemic test. Result expressed in percentage of diameter variation.


Original Primary Outcome: change from baseline in endothelial function [ Time Frame: 6 months ]

measure of the variation of the endothelium dependent humeral artery flow mediated dilatation (FMD) between the inclusion and 6 months after the introduction of the treatment


Current Secondary Outcome:

  • change from baseline in endothelial glycocalyx thickness [ Time Frame: 6 months ]
    indirect measure of the glycocalyx thickness by using sublingual SDF (sidestream dark field) imaging
  • change from baseline in oxydative stress [ Time Frame: 6 months ]
    plasma levels of nitrites and TBARS (thiobarbituric acid reactive substance)
  • change from baseline in systemic inflammation [ Time Frame: 6 months ]
    plasma levels of TNFalpha
  • change from baseline in coagulation parameter [ Time Frame: 6 months ]
    Tissue factor plasmatic level
  • change from baseline in plasmatic level in hydroxychloroquine [ Time Frame: 6 months ]
    plasma level of hydroxychloroquine


Original Secondary Outcome:

  • change from baseline in endothelial glycocalyx thickness [ Time Frame: 6 months ]
    indirect measure of the glycocalyx thickness by using sublingual sdf imaging
  • change from baseline in oxydative stress [ Time Frame: 6 months ]
    plasma levels of nitrites and TBARS
  • change from baseline in systemic inflammation [ Time Frame: 6 months ]
    plasma levels of TNFalpha
  • change from baseline in coagulation parameter [ Time Frame: 6 months ]
    Tissue factor plasmatic level
  • change from baseline in plasmatic level in hydroxychloroquine [ Time Frame: 6 months ]
    plasma level of hydroxychloroquine


Information By: University Hospital, Rouen

Dates:
Date Received: November 2, 2015
Date Started: June 2016
Date Completion: December 2018
Last Updated: December 6, 2016
Last Verified: December 2016