Nano-rheological Biomarkers for Patients With Sickle Cell Disease (SCD) Versus Control Subjects (Other Constitutional Red Blood Cell Diseases and Healthy Subjects)
NCT ID: NCT05530239
Last Updated: 2022-09-22
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
NOT_YET_RECRUITING
Total Enrollment
40 participants
Study Classification
OBSERVATIONAL
Study Start Date
2022-10-31
Study Completion Date
2025-11-30
Brief Summary
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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.
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.
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Detailed Description
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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.
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.
Conditions
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Sickle Cell Disease
Study Design
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Observational Model Type
CASE_CONTROL
Study Time Perspective
PROSPECTIVE
Study Groups
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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
Blood sample collection
Intervention Type
OTHER
Blood sample collection
SCD patients
Patients with SCD
Blood sample collection
Intervention Type
OTHER
Blood sample collection
Control patients
With a constitutional non-sickle cell disease of the red blood cell, or an acquired red blood cell disease.
Blood sample collection
Intervention Type
OTHER
Blood sample collection
Interventions
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Blood sample collection
Blood sample collection
Intervention Type
OTHER
Eligibility Criteria
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Inclusion Criteria
1. Patient age ≥ 18 years
2. With social care protection
3. Living donor recruited for kidney donation with normal blood count
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
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...)
2. With social care protection
3. Living donor recruited for kidney donation with normal blood count
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
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
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.
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.
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.
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.
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.
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.
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.
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.
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
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University Hospital, Grenoble
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Caroline MAKOWSKI, mD
Role: PRINCIPAL_INVESTIGATOR
CHU Grenoble Alpes
Central Contacts
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References
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Arlet JB. [A new therapeutic era in sickle cell disease]. Rev Med Interne. 2017 Sep;38(9):569-571. doi: 10.1016/j.revmed.2017.05.006. Epub 2017 Jun 16. No abstract available. French.
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Ballas SK. The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease. Mediterr J Hematol Infect Dis. 2020 Jan 1;12(1):e2020010. doi: 10.4084/MJHID.2020.010. eCollection 2020.
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Bartolucci P, Brugnara C, Teixeira-Pinto A, Pissard S, Moradkhani K, Jouault H, Galacteros F. Erythrocyte density in sickle cell syndromes is associated with specific clinical manifestations and hemolysis. Blood. 2012 Oct 11;120(15):3136-41. doi: 10.1182/blood-2012-04-424184. Epub 2012 Aug 23.
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Du E, Diez-Silva M, Kato GJ, Dao M, Suresh S. Kinetics of sickle cell biorheology and implications for painful vasoocclusive crisis. Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1422-7. doi: 10.1073/pnas.1424111112. Epub 2015 Jan 20.
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Holmes D, Whyte G, Bailey J, Vergara-Irigaray N, Ekpenyong A, Guck J, Duke T. Separation of blood cells with differing deformability using deterministic lateral displacement(dagger). Interface Focus. 2014 Dec 6;4(6):20140011. doi: 10.1098/rsfs.2014.0011.
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Kaul DK, Fabry ME, Windisch P, Baez S, Nagel RL. Erythrocytes in sickle cell anemia are heterogeneous in their rheological and hemodynamic characteristics. J Clin Invest. 1983 Jul;72(1):22-31. doi: 10.1172/jci110960.
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Lipowsky HH, Cram LE, Justice W, Eppihimer MJ. Effect of erythrocyte deformability on in vivo red cell transit time and hematocrit and their correlation with in vitro filterability. Microvasc Res. 1993 Jul;46(1):43-64. doi: 10.1006/mvre.1993.1034.
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Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. N Engl J Med. 2017 Apr 20;376(16):1561-1573. doi: 10.1056/NEJMra1510865. No abstract available.
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Ribeil JA, Hacein-Bey-Abina S, Payen E, Magnani A, Semeraro M, Magrin E, Caccavelli L, Neven B, Bourget P, El Nemer W, Bartolucci P, Weber L, Puy H, Meritet JF, Grevent D, Beuzard Y, Chretien S, Lefebvre T, Ross RW, Negre O, Veres G, Sandler L, Soni S, de Montalembert M, Blanche S, Leboulch P, Cavazzana M. Gene Therapy in a Patient with Sickle Cell Disease. N Engl J Med. 2017 Mar 2;376(9):848-855. doi: 10.1056/NEJMoa1609677.
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Other Identifiers
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38RC22.0135
Identifier Type: -
Identifier Source: org_study_id
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