Nano-rheological Biomarkers for Patients With Sickle Cell Disease (SCD) Versus Control Subjects (Other Constitutional Red Blood Cell Diseases and Healthy Subjects)

Not yet recruiting

• Conditions: Sickle Cell Disease
• Interventions: Other: Blood sample collection

• Registration Number: NCT05530239
• Lead Sponsor: University Hospital, Grenoble

Brief Summary

Numerous pathologies (sickle cell disease, thalassemia, spherocytosis, etc.) lead to changes in the rheological properties of the blood, in particular via alterations in the deformability of red blood cells. These alterations lead to circulatory complications of which an emblematic example is the sickle cell crisis which manifests itself by microcirculatory occlusions. Several authors suggest that the deformability of erythrocytes is a key parameter for the diagnosis and monitoring of patients. Numerous studies, especially in vitro, show that the mechanical properties of the red blood cell significantly influence its dynamics in flow (blood viscosity, distribution in capillary networks). Moreover, concerning the specific problem of vaso-occlusion, the proportion of the most rigid red blood cells is a determining factor of the probability of occlusion more than the average value of this rigidity which can hide great disparities.

There is no clinically usable test to assess the alteration of the fine rheology of the red blood cell in a patient. Functional tests such as ektacytometry require heavy equipment and teams of specialized biologists; this technique is therefore only available in 3 biological reference centers in France. "Mechanical phenotyping" seems to be a potentially simpler and more accessible technique, and has already shown promising prospects in other nosological settings than red blood cell pathologies.

Today, there is no specific marker of sickle cell vaso-occlusive crisis, nor marker of severity, that would be useful for pathophysiological understanding but also for clinical management.

Detailed Description

This study aims to characterize the microfluidic flow and intra-erythrocyte viscosity of sickle cell red blood cells, and to identify specific biological phenotype or clinical severity profiles. The techniques used are microfluidic circuits for the study of flow and molecular rotors for the measurement of intra-erythrocyte viscosity, using deoxygenation cycles in order to model physio-pathological situations.

The first part will allow the calibration of the microfluidic techniques used (microfluidic circuit and molecular rotors), testing blood from healthy subjects (without constitutional or acquired red blood cell pathology) and blood from SCD patients. The aim is to define the reproducibility and sensitivity of the techniques.

A second part is aimed at establishing a rheological profile of the blood of patients with SCD in comparison with blood from control subjects, i.e. with other constitutional or acquired red blood cell pathology.

Study Timeline

• Status Verified: 2022-07
• Study First Submitted: 2022-07-25
• Study First Submitted QC: 2022-09-02
• Study First Posted: 2022-09-07
• Last Update Submitted: 2022-09-20
• Last Update Posted: 2022-09-22
• Study Start: 2022-10
• Primary Completion: 2024-03
• Study Completion: 2025-11

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
SCD patients	Blood sample collection	Patients with SCD
Control patients	Blood sample collection	With a constitutional non-sickle cell disease of the red blood cell, or an acquired red blood cell disease.
Healthy subjects	Blood sample collection	Subjects with no documented hematological pathology (neither constitutional nor acquired). From the recruitment of living kidney donors, transplantation unit of Grenoble Alpes University Hospital

Primary Outcome Measures

Name	Time	Method
Study of the intra-erythrocyte viscosity dispersion and rheological profile of red blood cells	30 months	Measure of the intra-erythrocyte viscosity dispersion using molecular rotors technique, study of rheological profile of red blood cells in microfluidic circuit : measure of the speed of flowing, and DI deformability Index \[DI = (L-W)/(L+W)\] of each red blood cell, DI dispersion in each sample, in basal state and after exposure to deoxygenation cycles of blood SCD patients versus control subjects.

Secondary Outcome Measures

Name	Time	Method
Study of the intra-erythrocyte viscosity dispersion and rheological profile of red blood cells	24 months	Measure of the intra-erythrocyte viscosity dispersion using molecular rotors technique, study of rheological profile of red blood cells in microfluidic circuit : measure of the speed of flowing, and DI deformability Index \[DI = (L-W)/(L+W)\] of each red blood cell, DI dispersion in each sample, in basal state and after exposure to deoxygenation cycles in different conditions : congenital red blood cell disorders, acquired red blood cell disorders and clinical events (vasoocclusive crisis, pregnancy, infection).