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

NCT01569334 | Unknown

• 2 other identifiers: 2010-A01145-342010 18
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (1)

• Analysis of endothelial lesion-repair biomarkers

  through phenotypic and quantitative analysis of circulating endothelial progenitors subsets and (repair potential)

  24 MONTHS

Secondary Outcomes (1)

• Analysis of anti endothelial NK innate immune responses parameters

  24 MONTTHS

Study Arms (3)

HTC with Cardiac allograft vasculopathy

OTHER

HTC:heart transplanted recipients

Biological: blood samples

HTR without Cardiac allograft vasculopathy

OTHER

Biological: blood samples

untransplanted

OTHER

Biological: blood samples

Interventions

blood samples BIOLOGICAL

HTC with Cardiac allograft vasculopathy; HTR without Cardiac allograft vasculopathy; untransplanted

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Hopitaux de Marseille

Marseille, France

Location

Related Publications (1)

• 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.

  PMID: 29097449 DERIVED

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• BERNARD BELAIGUES

  Assistance Publique hôpitaux de Marseille

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2011
• First Posted: April 3, 2012
• Study Start: February 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: November 1, 2014
• Last Updated: August 29, 2014

Record last verified: 2014-08

Locations

FR (1)