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

September 20, 2022 updated by: University Hospital, Grenoble

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Study population will be patient with sickle cell disease (SCD) in comparaison of two populations : healthy volunteers (living donor of kidney) and patient with a constitutional non-sickle cell disease of the red blood cell, or an acquired red blood cell disease

Description

Inclusion Criteria for healthy volunteers :

  1. Patient age ≥ 18 years
  2. With social care protection
  3. Living donor recruited for kidney donation with normal blood count

Inclusion Criteria for SDC patient :

  1. Patient age ≥ 18 years
  2. With social care protection
  3. SCD patient with documented phenotype: SS, S°, S+, SC, SLepore, SOrab, SDPundjab, ASantilles... with or without specific treatment

Inclusion Criteria for patient with a constitutional non-sickle cell disease of the red blood cell, or an acquired red blood cell disease :

  1. Patient age ≥ 18 years
  2. With social care protection

  3. With any of the following conditions :

    1. Patient being managed for anemia due to martial deficiency, and prior to oral or intravenous replacement therapy
    2. Patient being followed for myeloproliferative syndrome at diagnosis, and prior to any specific treatment (hemodilution or hydroxycarbamide or other specific treatment)
    3. A patient with a MCGRE other than a major sickle cell syndrome, whether or not under specific treatment
    4. Hemoglobinopathy: transfusion-dependent or independent thalassemias (major or intermediate), thalassemias minor, heterozygous sickle cell trait A/S, other heterozygous hemoglobin variants (C, E, Lepore...), hyperaffine hemoglobin
    5. Membrane disorders (hereditary spherocytosis)
    6. Canalopathies (stomatocytosis with dehydrated or hyperhydrated erythrocytes, melanesian ovalocytosis...)
    7. Enzyme deficiencies (G6PD, PK, GPI...)

Exclusion Criteria for all patients:

  1. Patient age < 18 years
  2. Subject under guardianship, or subject deprived of freedom
  3. Linguistic or literacy status not allowing for informed consent despite patient information in "Easy to Read and Understand" format

  4. Known history of HIV, HTLV, syphilis, or positive serology and active viral hepatitis B or C.

    Additional Exclusion Criteria for healthy volunteers :

  5. Abnormal blood count, or possible martial deficiency with ferritin levels below 50µg/l, or current treatment with hydroxycarbamide, or transfusion within 4 months prior to inclusion.

Additional Exclusion Criteria for SCD patient :

5) Treatment with hydroxycarbamide started less than 6 months ago 6) Anemia with hemoglobin level <60g/l in the absence of cardiorespiratory pathology, <70g/l in pregnancy, or in the presence of cardiorespiratory pathology that may alter the tolerance of anemia.

Additional Exclusion Criteria for patient with a constitutional non-sickle cell disease of the red blood cell, or an acquired red blood cell disease :

5) Anemia with hemoglobin level <60g/l, <70g/l in pregnancy, or in the presence of cardio-respiratory pathology that may alter the tolerance of anemia.

6) Diagnosis not finalized (in progress), or uncertain nosological framework, or diagnostic wandering.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Study of the intra-erythrocyte viscosity dispersion and rheological profile of red blood cells
Time Frame: 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.
30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Study of the intra-erythrocyte viscosity dispersion and rheological profile of red blood cells
Time Frame: 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).
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Investigators

  • Principal Investigator: Caroline MAKOWSKI, mD, Chu Grenoble Alpes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2022

Primary Completion (Anticipated)

March 1, 2024

Study Completion (Anticipated)

November 1, 2025

Study Registration Dates

First Submitted

July 25, 2022

First Submitted That Met QC Criteria

September 2, 2022

First Posted (Actual)

September 7, 2022

Study Record Updates

Last Update Posted (Actual)

September 22, 2022

Last Update Submitted That Met QC Criteria

September 20, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC22.0135

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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