Plasma DNA and Vascular Remodelling in Patients With Sickle Cell Disease (PADRE)

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

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Procedure: micro- and macro-circulatory vascular remodelling measures not practice in routine care; Procedure: Biological measures not practice in routine care

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Ile De France
    • Bobigny, Ile De France, France, 93009
      • Hôpital Avicenne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: sickle cell disease patients; 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; Vascular measures : reactive hyperaemia index (RHI) assessed by Endo-PAT, central aortic blood pressure, aortic augmentation index, carotid-femoral pulse wave velocity; Procedure: Biological measures not practice in routine care; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: ADDMEDICA SASA
• Investigators: Principal Investigator: LE JEUNE Sylvain, MD, Hôpital Avicenne

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2016
• Primary Completion (Actual): November 14, 2019
• Study Completion (Actual): November 14, 2019

Study Registration Dates

• First Submitted: March 18, 2016
• First Submitted That Met QC Criteria: March 23, 2016
• First Posted (Estimate): March 29, 2016

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 7, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hematologic Diseases; Genetic Diseases, Inborn; Pathological Conditions, Anatomical; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Vascular Remodeling
• Other Study ID Numbers: DRE-FR-15-1