Venous Thrombosis Biomarkers in Sickle Cell Disease and Sickle Cell Trait
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04349189|
Recruitment Status : Recruiting
First Posted : April 16, 2020
Last Update Posted : December 30, 2022
Venous thromboembolism (VTE) includes the abnormal clotting of blood in a deep vein of the upper or lower limbs (deep vein thrombosis) that may travel to and block a blood vessel in the lung (pulmonary embolism). Some people with sickle cell disease (SCD)-a red blood cell disorder-seem to be at greater risk for developing these blood clots. Researchers want to study the blood of people with SCD and VTE as well as healthy people to develop better treatments to prevent blood clots.
To study blood clotting in SCD because it is the most common cause of vascular death after a heart attack or stroke.
People ages 18-80 who have SCD (with or without a history of blood clots) or the trait for SCD, and healthy volunteers
Participants will be screened with medical history, physical exam, and medical records review. They will give blood samples.
Participants will have phone calls either every 3 months or once a year, for 2 years. They will give updates on their health. They may give additional medical records. The phone calls may last up to 30 minutes.
If participants have a VTE or pain crisis episode, they may visit the Clinical Center. These visits may last up to 4 hours. They will repeat the screening tests and give blood samples.
Some participants may be invited to take part in blood studies.
After 2 years, some participants will have a follow-up visit at the Clinical Center.
Participation will last for about 2 years.
|Condition or disease|
|Sickle Cell Disease Venous Thrombosis Sickle Cell Trait Hypercoagulable State Venous Thromboembolism|
Venous thromboembolism (VTE) the third most frequent cause of vascular mortality after myocardial infarction and stroke, occurs more frequently among Americans of African descent compared with other ethnic minorities in the US. VTEs are provoked by diverse risk factors but can be unprovoked in individuals with a hypercoagulable state, in whom there is a predisposition for thrombosis. Patients with Sickle Cell Disease (SCD) have added risk of VTE as the disease itself is a hypercoagulable state. VTE frequency is increased across the entire spectrum of SCD severity, in those experiencing both mild (HbSC patients) and severe sickling symptoms (HbSS/HbSbeta0 thalassemia patients). Studies show that up to 12% of patients with SCD have VTE events [deep vein thrombus (DVT) or pulmonary embolism (PE) or both] early in life by age 40, most of which are unprovoked. Moreover, owing to a persistent hypercoagulable state, SCD patients are at an unacceptably high risk for recurrence, particularly those in whom VTE was unprovoked. SCD patients who develop a VTE have a 24.1% risk of recurrence over 5 years. A history of a VTE in SCD is associated with greater mortality risk (Odd Ratio, OR = 2.88; Confidence Interval, CI = 2.35 - 3.52).
Our overall hypothesis is that the proinflammatory state associated with SCD perturbs the coagulation system and contributes to the thrombotic vascular pathobiology of SCD. Abnormal intravascular tissue factor expressed on monocytes and endothelial cells and circulating tissue factor positive extracellular vesicles released by these cells drive coagulation activation in SCD. Specifically, intravascular tissue factor forms the tenase complex (TF:VIIa) which converts factor X to factor Xa, generating the initial thrombin burst that possibly triggers intravascular thrombosis. Besides, heightened tissue factor exposure during acute sickling crises, increased release of tissue factor positive extracellular vesicles and inadequate clearance of the latter favors thrombin generation, fibrin deposition and thrombosis in the venous vasculature. SCD patients with VTE and/or recurrent VTE are therefore more likely to have more tissue factor positive extracellular vesicles and plasma tissue factor procoagulant activity compared with SCD patients without VTE.
Prospective cohort studies of extended duration/indefinite anticoagulation in non-SCD patients with an underlying hypercoagulable state have effectively reduced recurrence rates. However, similar studies of extended duration anticoagulation in SCD patients are lacking. Besides, whether exposing SCD patients to extended/indefinite anticoagulation increases bleeding risk to unacceptably high levels is unknown. Studying thrombogenic risk and specifically identifying those SCD patients who are at greatest risk for VTE recurrence therefore becomes a high priority. In addition, individuals with sickle cell trait are prone to thrombosis but few studies evaluate markers of thrombotic risk in these individuals. Such studies could provide a rationale for targeted primary or secondary VTE prophylaxis.
In the current proposal we will test the hypothesis that plasma tissue factor positive extracellular vesicles and tissue factor activity are elevated among SCD patients with VTE compared with SCD patients without VTE and in individuals with Sickle Cell Trait compared with ethnically matched controls.
|Study Type :||Observational|
|Estimated Enrollment :||300 participants|
|Official Title:||Venous Thrombosis Biomarkers in Sickle Cell Disease and Sickle Cell Trait|
|Actual Study Start Date :||September 1, 2020|
|Estimated Primary Completion Date :||December 15, 2024|
|Estimated Study Completion Date :||October 15, 2026|
50 Men and Women with sickle cell disease and VTE
50 Men and Women with sickle cell disease but no VTE
50 Men and Women with sickle cell trait
50 ethnically matched Men and Women without sickle cell disease, sickle cell trait, or VTE
- tissue factor positive [ Time Frame: At baseline during study ]Number of tissue factor positive EVs/ml of plasma
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04349189
|Contact: Dianna Lovins||(301) email@example.com|
|Contact: Arun S Shet, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Arun S Shet, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|