Red Blood Cell Survival in Sickle Cell Disease
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|ClinicalTrials.gov Identifier: NCT04426591|
Recruitment Status : Recruiting
First Posted : June 11, 2020
Last Update Posted : November 3, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease||Drug: Biotin Labeled Red Blood Cells||Phase 1|
Sickle cell disease (SCD) carries significant morbidity as a result of red blood cell (RBC) sickling and hemolysis. Stroke is one of the most devastating sequelae of SCD. Chronic transfusion therapy (CTT) reduces stroke risk by (1) supplying normal, non-sickle RBC to circulation, thereby reducing the percentage of endogenous sickle RBC in circulation, and (2) maintaining a higher hemoglobin (Hb), thereby suppressing erythropoiesis of new sickle RBC. While the efficacy of CTT in stroke prophylaxis is well-established, nearly 45% of children continue to have silent or overt strokes despite CTT. The failure of CTT to prevent stroke events may be related to inadequate reduction of circulating sickle RBC and erythropoiesis. The amount of circulating sickle-RBC is related to the survival kinetics of both transfused RBC and endogenous sickle RBC.
In a large, longitudinal analysis of CTT in SCD, the researchers found wide variation in the survival of donor RBC following transfusion, with faster clearance associated with patient immune features (historical RBC alloimmunization and spleen presence) and with donor RBC glucose-6-phosphate-dehydrogenase (G6PD) deficiency. To better understand the roles of patient and donor factors in the survival and clearance of transfused RBC, the researchers propose a mechanistic, clinical trial during chronic transfusion episodes in patients with SCD, in which a small aliquot of each transfused unit is labeled with biotin conjugated to RBC surface proteins, to safely identify and measure the in vivo survival of donor RBC.
Aim 1 will examine the relationships of the recipient's immune system (past alloimmunization, splenic volume, and markers of reticuloendothelial system function) on the post-transfusion survival of biotin-labeled donor RBC.
Aim 2 will examine the relationships of donor RBC G6PD levels and donor RBC metabolomics with the in vivo survival and changes in donor RBC senescence markers. Completion of these aims will increase the understanding of mechanisms for the variability in RBC survival during CTT, identifying donor and recipient risk factors for decreased RBC survival. Ultimately this knowledge will inform the management of CTT to improve the prevention of strokes in SCD.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Kinetics of Donor Red Blood Cell Survival in Sickle Cell Disease|
|Actual Study Start Date :||October 29, 2021|
|Estimated Primary Completion Date :||May 2025|
|Estimated Study Completion Date :||May 2025|
Experimental: Biotin labeled Red Blood Cells
Participants receiving a transfusion with biotin labeled RBCs. Samples will be taken for 12 weeks after the biotinylated transfusion. During this time participants will continue to receive regular monthly transfusions (non-biotinylated) as part of CTT.
Drug: Biotin Labeled Red Blood Cells
On the day of transfusion, a 20 mL aliquot will be sterilely withdrawn from each RBC unit, washed and labeled with sulfo-NHS-biotin for 30 minutes, washed to stop the labeling reaction, then resuspended in plasma to a hematocrit of ~60%. The biotin-labeled RBC (BioRBC) will be transfused along with the remainder of the RBC unit (unlabeled volume). Standard blood bank and CTT protocols and minor antigen matching for SCD patients will be followed. Exact transfusion volume will be determined based on pre-transfusion Hb, HbS, and body weight, per clinical protocol.
- Change in Number of Biotin Labeled RBCs [ Time Frame: Day 1, Weeks 1-12 ]Survival of the transfused biotin labeled RBCs will be assessed as the count of biotinylated RBCs per sample.
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|Ages Eligible for Study:||6 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- HbSS or HbSβ0 thalassemia SCD
- receiving CTT for ≥3 months prior to enrollment
- anticipated cessation of CTT in the next ≤2 months
- concurrent hydroxyurea therapy
- automated RBC exchange therapy within 3 months prior to enrollment or anticipated within the next 3 months
- delayed hemolytic transfusion reaction in the past 3 months
- consuming high-dose biotin or raw egg supplements
- current pregnancy
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): NCT04426591
|Contact: Marianne Yee, MD||404-785-6190||Marianne.Yee@choa.org|
|United States, Georgia|
|Hughes Spalding Children's Hospital||Recruiting|
|Atlanta, Georgia, United States, 30303|
|Childrens Healthcare of Atlanta||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Grady Health System||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Principal Investigator:||Marianne Yee, MD||Emory University|
|Responsible Party:||John D Roback, Professor, Emory University|
|Other Study ID Numbers:||
1K23HL146904 ( U.S. NIH Grant/Contract )
|First Posted:||June 11, 2020 Key Record Dates|
|Last Update Posted:||November 3, 2021|
|Last Verified:||November 2021|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||All of the individual participant data collected during the trial will be made available for sharing with other researchers, after deidentification.|
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
|Time Frame:||Individual participant data will be made available for sharing immediately following publication, with no end date.|
|Access Criteria:||Data will be available for sharing with researchers who provide a methodologically sound proposal, for the purpose of achieving the aims in the approved proposal. Proposals should be directed to Marianne.Yee@choa.org. To gain access, data requestors will need to sign a data access agreement.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Vitamin B Complex
Physiological Effects of Drugs