Identification of Non Invasive Biomarkers of Immune Endothelial Injury and Repair Associated With Cardiac Allograft Vasculopathy

Cardiac Allograft Vasculopathy Clinical Trial

Official title:

Identification of Non Invasive Biomarkers of Immune Endothelial Injury and Repair Associated With Cardiac Allograft Vasculopathy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01569334
• Other study ID #: 2010-A01145-34
• Secondary ID: 2010 18
• Status: Active, not recruiting
• Phase: N/A
• First received: February 14, 2011
• Last updated: August 28, 2014
• Start date: February 2011
• Est. completion date: November 2014

Study information

• Verified date: August 2014
• Source: Assistance Publique Hopitaux De Marseille
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 170
• Est. completion date: November 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Cardiac Allograft Vasculopathy
• Vascular Diseases

Intervention

Biological:
• blood samples

Locations

Country	Name	City	State
France	Assistance Publique Hopitaux de Marseille	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analysis of endothelial lesion-repair biomarkers	through phenotypic and quantitative analysis of circulating endothelial progenitors subsets and (repair potential)	24 MONTHS	No
Secondary	Analysis of anti endothelial NK innate immune responses parameters	Anti endothelial, anti HLA anti MIC antibody detection in recipient' serum by luminex and flow cytometry; Evaluation of soluble Fractalkine and MIC levels in serum through ELISA; Analysis of CX3CR1 and CD16 polymorphism and phenotypic NK cell surface expression; Assay of serum induced and natural NK cell cytotoxicity against coronary and endothelial cell targets	24 MONTTHS	No