Plasma DNA and Vascular Remodelling in Patients With Sickle Cell Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the relationship between plasma DNA levels and micro- and macro-circulatory vascular remodelling in patients with sickle cell disease

Official Title
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Plasma DNA and Vascular Remodelling in Patients With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Procedure: micro- and macro-circulatory vascular remodelling measures not practice in routine care
* Procedure: Biological measures not practice in routine care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Homozygous SS or Sß0 sickle cell disease patients. Seen in consultation for an annual clinical and para-clinical evaluation of his/her disease. Stable clinical condition of the disease defined as the absence of severe vaso-occlusive crises (requiring hospitalisation or a visit to the emergency unit) in the previous month and absence of transfusion in the previous 3 months. Exclusion Criteria: Other haemoglobinopathy Known diabetes. Recent administration of an anticoagulant treatment at curative doses (< 48h before inclusion), or platelet-inhibiting drugs (less than 1 week prior to inclusion). Recent transfusion (less than 3 months prior to inclusion). Pregnancy or post-partum (first 40 days after giving birth). Recent consumption of alcohol (less than 10h), coffee (less than 3h), and tobacco (less than 36h) before inclusion. Known infection with hepatitis B, C, and HIV infection. Known cancer or progressive blood disease. Known haemostasis or coagulation disorders. Progressive inflammatory or infectious diseases. Recent history (dating less than 3 months) of venous (pulmonary embolism, deep venous thrombosis) or arterial (acute coronary syndrome, stroke, peripheral arterial ischaemia) thromboembolic event. Adult patients subject to legal protection measures. Patients already involved in a therapeutic protocol. Patients not affiliated to a social security system. Non-inclusion criteria related to the technical requirements of the Endo-PAT: Known cardiac arrhythmia. Severe Raynaud's syndrome. Hand or arm deformity that prevents an EndoPAT analysis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: sickle cell disease patients<br>Sickle cell disease patients included in the study and Plasma DNA levels will be analyzed and compared in patients with a reactive hyperaemia index (RHI) < 1.67 (endothelial dysfunction) assessed by Endo-PAT 2000 versus those recorded in patients with a RHI ≥ 1.67 (no endothelial dysfunction). | Procedure: micro- and macro-circulatory vascular remodelling measures not practice in routine care<br>* Vascular measures : reactive hyperaemia index (RHI) assessed by Endo-PAT, central aortic blood pressure, aortic augmentation index, carotid-femoral pulse wave velocity<br>Procedure: Biological measures not practice in routine care<br>* Biological measures : Plasma DNA level, NETs (plasma nucleosome levels), Microparticules (MPs) (total, associated with red blood cells, neutrophils, platelets), haem (total and bound to MPs), Myeloperoxydase and elastase activity, neutrophils/DNA, Annexin A5, RNA and TSP1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of plasma DNA levels in patients with a reactive hyperaemia index (RHI) < 1.67 (endothelial dysfunction) assessed by Endo-PAT 2000 versus those recorded in patients with a RHI ≥ 1.67 (no endothelial dysfunction) |  | 1 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between plasma DNA levels and cerebral micro- and macro-angiopathy assessed by CT angiography or MRI angiography and transcranial Doppler ultrasound |  | 1 day | 
| Relationship between plasma DNA levels and cardiac damages |  | 1 day | 
| Relationship between plasma DNA levels and pulmonary blood pressure |  | 1 day | 
| Relationship between plasma DNA levels and macrocirculatory vascular measurements |  | 2 days | 
| Relationship between plasma DNA levels and nephropathy |  | 1 day | 
| Relationship between plasma DNA levels and a clinical index of the sickle cell disease severity in a stable condition |  | 1 day |