Clinical trial NCT01569334: Identification of Non Invasive Biomarkers of Immune Endothelial Injury and Repair Associated With Cardiac Allograft Vasculopathy
Official title: Identification of Non Invasive Biomarkers of Immune Endothelial Injury and Repair Associated With Cardiac Allograft Vasculopathy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cardiac Allograft Vasculopathy
Keywords: identify early non invasive markers that index the endothelial lesion/ regeneration potential in association with CAV in heart transplanted recipients (HTR)
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2012-04-03
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

Brief summary: Heart transplantation is the best option for patients with end-stage heart failure. Cardiac allograft vasculopathy (CAV) is the leading cause of death following cardiac transplantation and is not managed by current therapies. Its pathogenesis traduces in an accelerated form of coronary artery disease (CAD) with similarities to atherosclerosis but also particular features of endothelial dysfunction associated to the alloimmune conflict and humoral responses toward the graft. Intravascular ultrasound (IVUS) is the validated invasive method for late CAV diagnosis, but occurs lesions are established. Identification of reliable non-invasive early endothelial injury biomarkers that reflect mechanisms of cardiac damage thus remain a major challenge to optimize therapeutic management of post transplant morbidity. Endothelial dysfunction is a central feature of both CAV and CAD and results from a desquilibrium in the balance of endothelial lesion and repair that is partly controlled by recipient immune system. Through their expression of receptors sensing antibodies (FcR CD16) and endothelial stress-induced signals (CX3CR1 fractalkine receptor and NKG2D MICA receptors), Natural Killer (NK) cells represent effector cells with unique potential to generate both humoral and innate immune injury of graft endothelium.


Eligibility criteria: Inclusion Criteria:

* Subject \> 18 years at the time of the inclusion,
* Subject having benefited from a heart transplant more than 11 months ago in the service of cardiac surgery concerned whatever is the treatment to immunosuppresseur current
* Subject benefiting from a coronarography within the framework of their surveillance comment-Clerk's Office beyond 12 months
* Subject having given their consent
* Affiliated to the Social Security

  \* HTC with Cardiac allograft vasculopathy:
* Subject with coronaropathies diagnosed by the coronarography

  \* TC without Cardiac allograft vasculopathy:
* Subject without coronaropathies diagnosed by the coronarography

  \* untransplanted
* Untreated Subject by immunosuppresseurs
* Subject without antécédaent of transfusion
* Subject without history of transplantations
* Subject with coronaropathies diagnosed by a coronarography

Exclusion Criteria:

* Presenting a contraindication to the coronarography
* Subject refusing to practise the examination of coronarography
* Subject reaches(affects) of a cancer other one than cutaneous
* Subject achieves of hepatic Incapacity (ALAT and\\or ASAT \> 3N)

Primary outcomes:
measure: Analysis of endothelial lesion-repair biomarkers
timeFrame: 24 MONTHS
Secondary outcomes:
measure: Analysis of anti endothelial NK innate immune responses parameters
timeFrame: 24 MONTTHS
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille
Study officials:
affiliation: Assistance Publique hôpitaux de Marseille
name: BERNARD BELAIGUES
role: STUDY_DIRECTOR
References:
citation: Paul P, Picard C, Sampol E, Lyonnet L, Di Cristofaro J, Paul-Delvaux L, Lano G, Nicolino-Brunet C, Ravis E, Collart F, Dignat-George F, Dussol B, Sabatier F, Mouly-Bandini A. Genetic and Functional Profiling of CD16-Dependent Natural Killer Activation Identifies Patients at Higher Risk of Cardiac Allograft Vasculopathy. Circulation. 2018 Mar 6;137(10):1049-1059. doi: 10.1161/CIRCULATIONAHA.117.030435. Epub 2017 Nov 2.