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Sickle Cell DiseaseNCT02565082

Evaluation of the Hemostatic Potential in Sickle Cell Disease Patients

A study testing Blood sampling - healthy volunteers, Blood sampling - sickle cell patients arm - stable condition and Blood sampling - sickle cell patients arm- exsanguinotransfusion needed in people with Sickle Cell Disease, run by Brugmann University Hospital at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Sickle cell disease is a genetic disorder caused by a point mutation on the amino acid sequence of the β chain of hemoglobin. The most expressive and most frequent complication of the disease is vaso-occlusive crisis, dominated by a painful syndrome. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Sickle Cell Disease
What is being tested?
Blood sampling - healthy volunteers, Blood sampling - sickle cell patients arm - stable condition and Blood sampling - sickle cell patients arm- exsanguinotransfusion needed
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
1 siteBelgium
Study dates
Sep 2015to Jul 2016
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Sickle cell disease group: Sickle cell disease patients aged over 18 years
  • Healthy volunteers group: Healthy volunteers, age matching with the sickle cell disease group

Who cannot join

  • Sickle cell disease group: Pregnant women, dialysis patients, patients with an hepatic impairment, patients under treatments that can interfere with coagulation
  • Healthy volunteers group: Pregnant women, known chronical disease, acute inflammatory syndrome, hemostasis disorder, abnormal complete blood count

Trial locations and contacts

1 site in 1 country.

Belgium1 site
  • CHU Brugmann Hospital

    Brussels, 1020

Other trials in Belgium

About this study

Sickle cell disease is a genetic disorder caused by a point mutation on the amino acid sequence of the β chain of hemoglobin.

The most expressive and most frequent complication of the disease is vaso-occlusive crisis, dominated by a painful syndrome. In addition to vaso-occlusive crises, many more chronic biological disturbances are observed in sickle cell patients.Sickle cell disease is considered nowadays as a hypercoagulable state.

Read more

However, the approach used so far to the measure of clotting in sickle cell disease was segmented in the sense that the various components of the hemostatic balance were studied separately.The thrombin generation test is a functional test which explores the coagulation globally, integrating both pro players that anticoagulants actors in the system. The investigators already used this test to demonstrate that the hemostatic potential was high in a cohort of affected children compared to control children of the same age.

This test will be used to characterize the hemostatic potential of adult sickle cell patients followed at the CHU Brugmann Hospital.

Read the detailed description

Sickle cell disease is a genetic disorder caused by a point mutation on the amino acid sequence of the β chain of hemoglobin. This is the most common genetic disease in the world. The majority of patients are in Sub-Saharan Africa; however, the increase in migratory movements of populations helps to move patients out of the initial zones of the disease.

According to recent data, about 400 patients would be followed in the Belgian hospitals, and about 1 in 1500 newborns in Belgium would be a major carrier of hemoglobinopathies. The most expressive and most frequent complication of the disease is vaso-occlusive crisis, dominated by a painful syndrome. In addition to vaso-occlusive crises, many more chronic biological disturbances are observed in sickle cell patients. Their contribution to the course of the disease is becoming increasingly stressing. Among them are intravascular hemolysis, hyper-adhesion of blood cells to vascular endothelium, inflammation, oxidative stress, vasculopathy and bleeding disorders.

Sickle cell disease is considered nowadays as a hypercoagulable state. Indeed, sickle cell patients have a high risk of non-hemorrhagic stroke, thrombosis in the pulmonary arteries and deep vein thrombosis that are otherwise associated with mortality and high morbidity. Many anomalies at various levels in the hemostatic system demonstrate coagulation activation even in clinically stable condition.

However, the approach used so far to the measure of clotting in sickle cell disease was segmented in the sense that the various components of the hemostatic balance were studied separately. This scale is complex, this approach difficult to give a comprehensive and integrated picture of the various disturbances in the system. The thrombin generation test is a functional test which explores the coagulation globally, integrating both pro players that anticoagulants actors in the system. The investigators have used this test to demonstrate that the hemostatic potential was high in a cohort of affected children compared to control children of the same age. In this cohort high hemostatic potential was related to the rate of circulating microparticles and intravascular hemolysis rate. Studies are underway to look for correlations between the hemostatic potential and clinical complications in this pediatric cohort.

The use of thrombin generation test for the study of hemostasis in adult patients with sickle cell disease, and the contribution of coagulation disorders with the occurrence of complications of the disease remain little known. The investigators will therefore:

  • Characterize the hemostatic potential of adult sickle cell patients followed at the CHU Brugmann
  • Search for links between the hemostatic potential and other biological phenomena observed during the disease (intravascular hemolysis, microparticles, vasculopathy, inflammation)
  • Search for correlations with clinical complications
  • Evaluate the effect of treatment (including exchange transfusions) on the hemostatic potential.
Being tested
Blood sampling - healthy volunteers, Blood sampling - sickle cell patients arm - stable condition, Blood sampling - sickle cell patients arm- exsanguinotransfusion needed, Blood sampling - sickle cell patients arm - vaso-occlusive crisis.
Keywords
Hemostatic potential, Sickle cell disease, Thrombin generation test
Medical subject headings
Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood sampling - healthy volunteersOther

    Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once.

  • Blood sampling - sickle cell patients arm - stable conditionOther

    Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once.

  • Blood sampling - sickle cell patients arm- exsanguinotransfusion neededOther

    Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once, before and after the exsanguinotransfusion.

  • Blood sampling - sickle cell patients arm - vaso-occlusive crisis.Other

    Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once.

Study groups in NCT02565082
Study groupRoleWhat they receive
Sickle cell diseaseExperimentalThis arm will include an approximate number of 50 sickle cell disease patients, homozygous and heterozygous.
Receives: Other: Blood sampling - sickle cell patients arm - stable condition; Other: Blood sampling - sickle cell patients arm- exsanguinotransfusion needed; Other: Blood sampling - sickle cell patients arm - vaso-occlusive crisis.
ControlOtherThis arm will include an approximate number of 30 healthy volunteers.
Receives: Other: Blood sampling - healthy volunteers

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Coagulation markers

    The following coagulation markers will be assessed in the blood samples: thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time

  2. Coagulation markers

    The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time

  3. Coagulation markers

    The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time

  4. Coagulation markers

    The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time

  5. Coagulation markers

    The following markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each volunteer.

    Measured: healthy volunteers: after informed consent signature, within maximum two years time

  6. Hemolysis markers

    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time

  7. Hemolysis markers

    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time

  8. Hemolysis markers

    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time

  9. Hemolysis markers

    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time

  10. Hemolysis markers

    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each volunteer.

    Measured: healthy volunteers: after informed consent signature, within maximum two years time

  11. Microparticles level

    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time

  12. Microparticles level

    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS. This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients -if exsanguinotransfusion - immediately prior exsanguinotransfusion, within maximum two years time

  13. Microparticles level

    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time

  14. Microparticles level

    Will be measured both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time

  15. Microparticles level

    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS. This will be measured only once for each patient, for this health status.

    Measured: healthy volunteers: after informed consent signature, within maximum two years time

  16. Inflammatory markers

    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time

  17. Inflammatory markers

    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time

  18. Inflammatory markers

    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time

  19. Inflammatory markers

    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.

    Measured: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time

  20. Inflammatory markers

    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each volunteer.

    Measured: healthy volunteers - after informed consent signature, within maximum two years time

  21. Vascular markers

    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status

    Measured: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time

  22. Vascular markers

    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status

    Measured: sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time

  23. Vascular markers

    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status

    Measured: sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time

  24. Vascular markers

    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each volunteer.

    Measured: healthy volunteers - after informed consent signature, within maximum two years time

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2015 (estimated)
  2. Study startSep 2015
  3. Primary completionJul 2016
  4. Study completionJul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02565082
Sponsor's protocol ID
CHUB-Drepanocytose-Hemostatic
Status last verified
Jul 2016
First submitted
18 Sep 2015
Last updated
26 Jul 2016
Results posted
No
Data monitoring committee
No

Publications

  • Le PQ, Ferster A, Cotton F, Vertongen F, Vermylen C, Vanderfaeillie A, Dedeken L, Heijmans C, Ketelslegers O, Dresse MF, Gulbis B. Sickle cell disease from Africa to Belgium, from neonatal screening to clinical management. Med Trop (Mars). 2010 Dec;70(5-6):467-70.

    PubMed 21516988
  • Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010 Dec 11;376(9757):2018-31. doi: 10.1016/S0140-6736(10)61029-X. Epub 2010 Dec 3.

    PubMed 21131035
  • Ataga KI, Key NS. Hypercoagulability in sickle cell disease: new approaches to an old problem. Hematology Am Soc Hematol Educ Program. 2007:91-6. doi: 10.1182/asheducation-2007.1.91.

    PubMed 18024615
  • De Franceschi L, Cappellini MD, Olivieri O. Thrombosis and sickle cell disease. Semin Thromb Hemost. 2011 Apr;37(3):226-36. doi: 10.1055/s-0031-1273087. Epub 2011 Mar 31.

    PubMed 21455857
  • Manci EA, Culberson DE, Yang YM, Gardner TM, Powell R, Haynes J Jr, Shah AK, Mankad VN; Investigators of the Cooperative Study of Sickle Cell Disease. Causes of death in sickle cell disease: an autopsy study. Br J Haematol. 2003 Oct;123(2):359-65. doi: 10.1046/j.1365-2141.2003.04594.x.

    PubMed 14531921
  • Hemker HC, Giesen P, Al Dieri R, Regnault V, de Smedt E, Wagenvoord R, Lecompte T, Beguin S. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb. 2003;33(1):4-15. doi: 10.1159/000071636.

    PubMed 12853707
  • Noubouossie DF, Le PQ, Corazza F, Debaugnies F, Rozen L, Ferster A, Demulder A. Thrombin generation reveals high procoagulant potential in the plasma of sickle cell disease children. Am J Hematol. 2012 Feb;87(2):145-9. doi: 10.1002/ajh.22206. Epub 2011 Nov 4.

    PubMed 22052675
  • Noubouossie DC, Le PQ, Rozen L, Debaugnies F, Ferster A, Demulder A. Evaluation of the procoagulant activity of endogenous phospholipids in the platelet-free plasma of children with sickle cell disease using functional assays. Thromb Res. 2012 Aug;130(2):259-64. doi: 10.1016/j.thromres.2011.10.016. Epub 2011 Nov 12.

    PubMed 22079446

Questions about this trial

What is this clinical trial studying?

A study testing Blood sampling - healthy volunteers, Blood sampling - sickle cell patients arm - stable condition and Blood sampling - sickle cell patients arm- exsanguinotransfusion needed in people with Sickle Cell Disease, run by Brugmann University Hospital at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Coagulation markers (time frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time). The study lists 24 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02565082, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2016.

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