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

NCT05530239 | Unknown

• 1 other identifier: 38RC22.0135
• Study Type: observational
• Target: 40
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Sickle Cell Disease

Keywords

Hemorheology; Microfluidics; Blood viscosity; Red blood cell; Sickle cell disease

Outcome Measures

Primary Outcomes (1)

• Study of the intra-erythrocyte viscosity dispersion and rheological profile of red blood cells

  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 Outcomes (1)

• Study of the intra-erythrocyte viscosity dispersion and rheological profile of red blood cells

  24 months

Study Arms (3)

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

SCD patients

Patients with SCD

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.

Other: Blood sample collection

Interventions

Blood sample collection OTHER

Blood sample collection

Control patients; Healthy subjects; SCD patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• Patient age ≥ 18 years
• With social care protection
• Living donor recruited for kidney donation with normal blood count
• Patient age ≥ 18 years
• With social care protection
• SCD patient with documented phenotype: SS, S°, S+, SC, SLepore, SOrab, SDPundjab, ASantilles... with or without specific treatment
• Patient age ≥ 18 years
• With social care protection
• With any of the following conditions :
• Patient being managed for anemia due to martial deficiency, and prior to oral or intravenous replacement therapy
• Patient being followed for myeloproliferative syndrome at diagnosis, and prior to any specific treatment (hemodilution or hydroxycarbamide or other specific treatment)
• A patient with a MCGRE other than a major sickle cell syndrome, whether or not under specific treatment
• 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
• Membrane disorders (hereditary spherocytosis)
• Canalopathies (stomatocytosis with dehydrated or hyperhydrated erythrocytes, melanesian ovalocytosis...)

You may not qualify if:

• Patient age \< 18 years
• Subject under guardianship, or subject deprived of freedom
• Linguistic or literacy status not allowing for informed consent despite patient information in "Easy to Read and Understand" format
• Known history of HIV, HTLV, syphilis, or positive serology and active viral hepatitis B or C.
• \) 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.
• \) 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.
• \) Diagnosis not finalized (in progress), or uncertain nosological framework, or diagnostic wandering.

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Related Publications (30)

• 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.

  PMID: 28624233 BACKGROUND

• Ataga KI, Kutlar A, Kanter J. Crizanlizumab in Sickle Cell Disease. N Engl J Med. 2017 May 4;376(18):1796. doi: 10.1056/NEJMc1703162. No abstract available.

  PMID: 28467874 BACKGROUND

• Ballas SK, Barton FB, Waclawiw MA, Swerdlow P, Eckman JR, Pegelow CH, Koshy M, Barton BA, Bonds DR. Hydroxyurea and sickle cell anemia: effect on quality of life. Health Qual Life Outcomes. 2006 Aug 31;4:59. doi: 10.1186/1477-7525-4-59.

  PMID: 16942629 BACKGROUND

• 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.

  PMID: 31934320 BACKGROUND

• Baez S, Kaul DK, Nagel RL. Microvascular determinants of blood flow behavior and HbSS erythrocyte plugging in microcirculation. Blood Cells. 1982;8(1):127-37. No abstract available.

  PMID: 7115970 BACKGROUND

• Banerjee R, Nageshwari K, Puniyani RR. The diagnostic relevance of red cell rigidity. Clin Hemorheol Microcirc. 1998 Sep;19(1):21-4.

  PMID: 9806729 BACKGROUND

• 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.

  PMID: 22919030 BACKGROUND

• Briole A, Podgorski T, Abou B. Molecular rotors as intracellular probes of red blood cell stiffness. Soft Matter. 2021 May 5;17(17):4525-4537. doi: 10.1039/d1sm00321f.

  PMID: 33949619 BACKGROUND

• Connes P, Alexy T, Detterich J, Romana M, Hardy-Dessources MD, Ballas SK. The role of blood rheology in sickle cell disease. Blood Rev. 2016 Mar;30(2):111-8. doi: 10.1016/j.blre.2015.08.005. Epub 2015 Aug 28.

  PMID: 26341565 BACKGROUND

• 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.

  PMID: 25605910 BACKGROUND

• Faivre M, Renoux C, Bessaa A, Da Costa L, Joly P, Gauthier A, Connes P. Mechanical Signature of Red Blood Cells Flowing Out of a Microfluidic Constriction Is Impacted by Membrane Elasticity, Cell Surface-to-Volume Ratio and Diseases. Front Physiol. 2020 Jun 12;11:576. doi: 10.3389/fphys.2020.00576. eCollection 2020.

  PMID: 32595519 BACKGROUND

• Gladwin MT, Vichinsky E. Pulmonary complications of sickle cell disease. N Engl J Med. 2008 Nov 20;359(21):2254-65. doi: 10.1056/NEJMra0804411. No abstract available.

  PMID: 19020327 BACKGROUND

• Guo Q, Duffy SP, Matthews K, Santoso AT, Scott MD, Ma H. Microfluidic analysis of red blood cell deformability. J Biomech. 2014 Jun 3;47(8):1767-76. doi: 10.1016/j.jbiomech.2014.03.038. Epub 2014 Apr 5.

  PMID: 24767871 BACKGROUND

• Gossett DR, Tse HT, Lee SA, Ying Y, Lindgren AG, Yang OO, Rao J, Clark AT, Di Carlo D. Hydrodynamic stretching of single cells for large population mechanical phenotyping. Proc Natl Acad Sci U S A. 2012 May 15;109(20):7630-5. doi: 10.1073/pnas.1200107109. Epub 2012 Apr 30.

  PMID: 22547795 BACKGROUND

• Hamideh D, Alvarez O. Sickle cell disease related mortality in the United States (1999-2009). Pediatr Blood Cancer. 2013 Sep;60(9):1482-6. doi: 10.1002/pbc.24557. Epub 2013 Apr 23.

  PMID: 23637037 BACKGROUND

• 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.

  PMID: 25485078 BACKGROUND

• 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.

  PMID: 6874947 BACKGROUND

• Kaul DK, Fabry ME. In vivo studies of sickle red blood cells. Microcirculation. 2004 Mar;11(2):153-65.

  PMID: 15280089 BACKGROUND

• Kuimova MK, Yahioglu G, Levitt JA, Suhling K. Molecular rotor measures viscosity of live cells via fluorescence lifetime imaging. J Am Chem Soc. 2008 May 28;130(21):6672-3. doi: 10.1021/ja800570d. Epub 2008 May 6.

  PMID: 18457396 BACKGROUND

• Lanzkron S, Carroll CP, Haywood C Jr. Mortality rates and age at death from sickle cell disease: U.S., 1979-2005. Public Health Rep. 2013 Mar-Apr;128(2):110-6. doi: 10.1177/003335491312800206.

  PMID: 23450875 BACKGROUND

• 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.

  PMID: 8412852 BACKGROUND

• Lu X, Chaudhury A, Higgins JM, Wood DK. Oxygen-dependent flow of sickle trait blood as an in vitro therapeutic benchmark for sickle cell disease treatments. Am J Hematol. 2018 Oct;93(10):1227-1235. doi: 10.1002/ajh.25227. Epub 2018 Aug 21.

  PMID: 30033564 BACKGROUND

• Niihara Y, Miller ST, Kanter J, Lanzkron S, Smith WR, Hsu LL, Gordeuk VR, Viswanathan K, Sarnaik S, Osunkwo I, Guillaume E, Sadanandan S, Sieger L, Lasky JL, Panosyan EH, Blake OA, New TN, Bellevue R, Tran LT, Razon RL, Stark CW, Neumayr LD, Vichinsky EP; Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. N Engl J Med. 2018 Jul 19;379(3):226-235. doi: 10.1056/NEJMoa1715971.

  PMID: 30021096 BACKGROUND

• 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.

  PMID: 28423290 BACKGROUND

• 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.

  PMID: 28249145 BACKGROUND

• Tomaiuolo G. Biomechanical properties of red blood cells in health and disease towards microfluidics. Biomicrofluidics. 2014 Sep 17;8(5):051501. doi: 10.1063/1.4895755. eCollection 2014 Sep.

  PMID: 25332724 BACKGROUND

• Telen MJ. Developing new pharmacotherapeutic approaches to treating sickle-cell disease. ISBT Sci Ser. 2017 Feb;12(1):239-247. doi: 10.1111/voxs.12305. Epub 2016 Nov 15.

  PMID: 28484512 BACKGROUND

• Vargas FF, Blackshear GL. Vascular resistance and transit time of sickle red blood cells. Blood Cells. 1982;8(1):139-45.

  PMID: 7115971 BACKGROUND

• Woodcock EM, Girvan P, Eckert J, Lopez-Duarte I, Kubankova M, van Loon JJWA, Brooks NJ, Kuimova MK. Measuring Intracellular Viscosity in Conditions of Hypergravity. Biophys J. 2019 May 21;116(10):1984-1993. doi: 10.1016/j.bpj.2019.03.038. Epub 2019 Apr 8.

  PMID: 31053255 BACKGROUND

• Yaginuma T, Oliveira MS, Lima R, Ishikawa T, Yamaguchi T. Human red blood cell behavior under homogeneous extensional flow in a hyperbolic-shaped microchannel. Biomicrofluidics. 2013 Sep 24;7(5):54110. doi: 10.1063/1.4820414. eCollection 2013.

  PMID: 24404073 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Caroline MAKOWSKI, mD

  CHU Grenoble Alpes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caroline MAKOWSKI, Md

CONTACT

+33476767640; cmakowski@chu-grenoble.fr

Bruna DUCOTTERD, CRA

CONTACT

+3376767838; bducotterd@chu-grenoble.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: September 7, 2022
• Study Start: October 1, 2022
• Primary Completion: March 1, 2024
• Study Completion: November 1, 2025
• Last Updated: September 22, 2022

Record last verified: 2022-07