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) (VASCUDREPA)

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

Study Overview

• Status: Completed
• Conditions: Sickle Cell Anemia
• Intervention / Treatment: Diagnostic test: 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)

Detailed Description

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
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Guadeloupe
  • Guadeloupe
    • Pointe-à-Pitre, Guadeloupe, Guadeloupe, 97159
      • Hospital University Center of Pointe-à-Pitre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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: functions micro and macro-vascular in connection the clinical; 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.

Diagnostic test: 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); 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	Assessed through study completion, average follow-up 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematological and Hemorheological Profile Complete blood count	Units: g/dL (hemoglobin),	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	Through study completion, average follow-up 3 years
Circulating Nitric Oxide Levels	Plasma concentration of nitric oxide metabolites. Units: μmol/L	Through study completion, average follow-up 3 years
Circulating Microparticles	Number and origin of circulating microparticles (platelet, leukocyte, erythrocyte, endothelial). Units: particles/μL	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)	Through study completion, average follow-up 3 years
Muscle and Cerebral Oxygenation	Oxygen saturation of muscle and brain tissue using near-infrared spectroscopy (NIRS). Units: % oxygen saturation	Through study completion, average follow-up 3 years
Physical Activity and Capacity 6-minute walk test distance	Units: meters (walk test),	Through study completion, average follow-up 3 years
Effect of Hydroxyurea on Vascular Function	Units: Perfusion units (microvascular), m/s (pulse wave velocity)	Through study completion, average follow-up 3 years
Hematological and Hemorheological Profile hematocrit	Units: % (hematocrit),	Thought study completion , an average of 3 years
Hematological and Hemorheological Profile blood viscosity parameters	mPa·s (blood viscosity)	Through study completion, an average of 3 years
Physical Activity and Capacity oxygen consumption (VO2)	mL/kg/min (VO2)	Through study completion, average follow-up 3 years
Physical Activity and Capacity Accelerometer	activity counts	Through study completion, average follow-up 3 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de la Guadeloupe
• Investigators: Principal Investigator: Marie BILLAUD, Doctor in the Sickle Cell, Hospital University Center of Pointe-à-Pitre

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2016
• Primary Completion (Actual): October 29, 2018
• Study Completion (Actual): October 29, 2021

Study Registration Dates

• First Submitted: November 27, 2017
• First Submitted That Met QC Criteria: December 10, 2025
• First Posted (Actual): December 11, 2025

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: sickle cell anemia; vascular dysfunction; hemoglobin C disease
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Hemoglobin C Disease
• Other Study ID Numbers: RBM-PAP-2015/108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No