The Influence of micro-and Macro Vascular Dysfunction on Clinical Severity in Adults With Sickle Cell Anemia (SS) and Sickle Cell Hemoglobin C Disease (SC)

Centre Hospitalier Universitaire de la Guadeloupe49 enrolled

Overview

The primary aim of this study is to determine the implication of micro and macro vascular function on the clinical severity of SCD (SS, SC, Sß°) adults. The secondary aim of this study is to understand the contribution of several parameters, known to influence vascular function in non-SCD individuals, in SCD

TSCD patients are characterized by vascular alterations, with vascular function being severely affected. However, the exact contribution of vascular dysfunction in the clinical severity and the risk for frequent vaso-occlusive crises in SCD is unknown. Furthermore the factors involved in this imbalance remain unclear but it is supposed that cerebral hypoxia, the deficit in nitric oxide, abnormal blood rheology, increased microparticles levels, autonomic nervous system imbalance and a low level of physical activity as well as poor physical fitness might be involved. * Primary outcome: The primary outcome of the present study is to characterize the level of alteration of micro and macro vascular function in SCD (SS, SC and Sß°) adults measured by heat-mediated vasodilation and peripheral perfusion (Laser Doppler system) and pulse wave velocity and to test relationships between this measured vascular function and clinical severity which is based on the rate of vaso-occlusive crisis (severe if ≥ 3 per year), the rate of acute chest syndrome (severe if \> 0 per year) and/or the presence of chronic complications. * Secondary outcomes: To test the existence of relationships between several factors: biological (hematology, blood rheology, nitric oxide and microparticles), physiological (the autonomic nervous system activity measured by Holter electrocardiogram and tissue oxygenation (muscular and cerebral)) and physical activity level (estimated by questionnaire and accelerometer) and physical fitness (estimated by the six minute walk test with oxygen consumption measurements). * Study design: This study has been designed as biomedical, monocentric prospective and interventional study

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Sickle Cell Anemia

Interventions

The influence of micro-and macro vascular dysfunction on clinical severity in adults with sickle cell anemia (SS) and sickle cell hemoglobin C disease (SC)DIAGNOSTIC_TEST

The study permit to characterize the level of alteration of micro and macro vascular function in SCD (SS, SC and Sß°) adults measured by heat-mediated vasodilation and peripheral perfusion (Laser Doppler system) and pulse wave velocity and to test relationships between this measured vascular function and clinical severity which is based on the rate of vaso-occlusive crisis (severe if ≥ 3 within the 2 preceding years) and the rate of acute chest syndrome (severe if \> 0 in the last 2 years).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * adults ≥ 18 years old, * medical diagnosed with SCD (genotype SS, SC or Sß°) by isoelectrofocusing or HPLC at clinical steady state at the time of the study (i.e., no blood transfusion within the last three months, * absence of acute episodes of infection, vaso-occlusive crisis or acute chest syndrome at least one month before inclusion in the study), * regularly followed by the Sickle Cell Unit of the Academic Hospital of Pointe-à-Pitre (Guadeloupe) and having signed well informed the letter of agreement. Exclusion Criteria: * not at "steady-state"; * pregnancy or breast feeding; * non-compliant patients to usual care; * no signed informed consent

Locations (1)

Hospital University Center of Pointe-à-Pitre

Pointe-à-Pitre, Guadeloupe, Guadeloupe

Outcomes

Primary Outcomes

Microvascular Function

What is measured: Peripheral microvascular function will be assessed using Laser Doppler flowmetry to measure hyperemia response induced by localized heat. Units: Perfusion units (PU)

Time frame: Through study completion, an average of 3 years

Macrovascular Function (Arterial Stiffness)

What is measured: Arterial rigidity will be evaluated using pulse wave velocity (PWV) measurements. Units: meters/second (m/s)

Time frame: Assessed through study completion, average follow-up 3 years

Secondary Outcomes

Hematological and Hemorheological Profile Complete blood count

Units: g/dL (hemoglobin),

Time frame: Through study completion, an average of 3 years

Oxidative Stress Profile

Plasma and erythrocyte markers of oxidative stress (e.g., malondialdehyde, glutathione). Units: μmol/L or standardized assay units

Time frame: Through study completion, average follow-up 3 years

Circulating Nitric Oxide Levels

Plasma concentration of nitric oxide metabolites. Units: μmol/L

Time frame: Through study completion, average follow-up 3 years

Circulating Microparticles

Number and origin of circulating microparticles (platelet, leukocyte, erythrocyte, endothelial). Units: particles/μL

Time frame: Through study completion, average follow-up 3 years

Autonomic Nervous System Activity

Heart rate variability (HRV) derived from Holter ECG recordings. Units: ms (standard deviation of NN intervals), normalized units (frequency domain parameters)

Data from ClinicalTrials.gov

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