Red Blood Cell Survival Study for Sickle Cell Disease
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Marianne Yee
Disqualifiers: Biotin, Raw egg supplements, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial aims to understand how long transfused red blood cells (RBCs) last in patients with sickle cell disease (SCD) who receive frequent blood transfusions. Researchers will label a small portion of the transfused RBCs with biotin to track their survival. The study will help identify factors that influence the effectiveness of these transfusions and improve treatment strategies.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, it does mention that ongoing consumption of biotin or raw egg dietary supplements is not allowed.
What data supports the effectiveness of the treatment Biotin Labeled Red Blood Cells for Sickle Cell Disease?
The research shows that biotin labeling is a reliable method for tracking the lifespan of red blood cells, which is important for understanding how sickle cells behave over time. This method has been validated against a standard labeling technique and is useful for studying red cell survival in conditions like sickle cell disease.
12345Is the use of biotin-labeled red blood cells safe for humans?
Studies have shown that using biotin-labeled red blood cells is generally safe for humans, with advantages over older methods. However, there have been occasional reports of antibodies forming against these labeled cells, which could affect their survival after transfusion.
24567How does the treatment Biotin Labeled Red Blood Cells differ from other treatments for sickle cell disease?
Biotin Labeled Red Blood Cells are unique because they allow for the tracking of red blood cell survival and lifespan without using radioactive materials, providing a safer and more precise method to study red blood cell dynamics in sickle cell disease.
23458Eligibility Criteria
This trial is for individuals with Sickle Cell Disease (SCD), specifically HbSS or HbSβ0 thalassemia, who have been receiving regular blood transfusions for at least 3 months. It's not suitable for those on hydroxyurea therapy, taking high-dose biotin or raw egg supplements, expecting to stop transfusions soon, having had certain blood exchange therapies or reactions recently, or are currently pregnant.Inclusion Criteria
I have been on hormone therapy for at least 3 months.
I have sickle cell disease, either HbSS or HbSβ0 thalassemia.
Exclusion Criteria
I am currently taking hydroxyurea.
current pregnancy
I expect to stop my current cancer treatment within 2 months.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive transfusions with biotin labeled RBCs and continue regular monthly transfusions as part of chronic transfusion therapy
12 weeks
Weekly visits for 3 months, then monthly for 3 months
Follow-up
Participants are monitored for the survival of transfused biotin labeled RBCs
Up to Day 70
Optional Sub-study
Participants may opt into a sub-study using INTERCEPT RBCs to compare survival and clearance rates
Participant Groups
The study tests how long transfused red blood cells last in patients with SCD undergoing chronic transfusion therapy. Participants will receive biotin-labeled RBCs during a normal transfusion and then be monitored regularly up to six months. An optional part of the study uses INTERCEPT-treated RBCs to compare survival rates.
1Treatment groups
Experimental Treatment
Group I: Biotin labeled Red Blood CellsExperimental Treatment2 Interventions
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.
Biotin Labeled Red Blood Cells is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Red Blood Cells for:
- Anemia due to blood loss
- Anemia due to chronic disease
- Sickle cell disease
🇪🇺 Approved in European Union as Red Blood Cells for:
- Anemia
- Blood component therapy
- Sickle cell disease
🇨🇦 Approved in Canada as Red Blood Cells for:
- Anemia
- Blood component therapy
- Sickle cell disease
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Hughes Spalding Children's HospitalAtlanta, GA
Childrens Healthcare of AtlantaAtlanta, GA
Grady Health SystemAtlanta, GA
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Who Is Running the Clinical Trial?
Marianne YeeLead Sponsor
Emory UniversityLead Sponsor
Cerus CorporationIndustry Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
The effect of fetal hemoglobin on the survival characteristics of sickle cells. [2021]The determinants of sickle red blood cell (RBC) life span have not been well-defined but may include both intrinsic factors (eg, the tendency to sickle) and extrinsic factors (eg, the capacity of the reticuloendothelial system to remove defective RBCs). Fetal hemoglobin (HbF) is heterogeneously distributed among sickle RBCs; F cells contain 20% to 25% HbF, whereas the remainder have no detectable HbF (non-F cells). Autologous sickle RBCs were labeled with biotin and reinfused to determine overall survival, non-F- and F-cell survival, and time-dependent changes in HbF content (%HbF) for the surviving F cells. A total of 10 patients were enrolled, including 2 who were studied before and after the percentage of F cells was increased by treatment with hydroxyurea. As expected, F cells survived longer in all subjects. Non-F-cell survival correlated inversely with the percentage of F cells, with the time for 30% cell survival ranging from 6 days in patients with more than 88% F cells to 16 days in patients with less than 16% F cells. As the biotin-labeled RBCs aged in the circulation, the HbF content of the surviving F-cell population increased by 0.28%/d +/- 0.21%/d, indicating that within the F-cell population those with higher HbF content survived longer.
Measurement of posttransfusion red cell survival with the biotin label. [2021]The goal of this review is to summarize and critically assess information concerning the biotin method to label red blood cells (RBC) for use in studies of RBC and transfusion biology-information that will prove useful to a broad audience of clinicians and scientists. A review of RBC biology, with emphasis on RBC senescence and in vivo survival, is included, followed by an analysis of the advantages and disadvantages of biotin-labeled RBC (BioRBC) for measuring circulating RBC volume, posttransfusion RBC recovery, RBC life span, and RBC age-dependent properties. The advantages of BioRBC over (51)Cr RBC labeling, the current reference method, are discussed. Because the biotin method is straightforward and robust, including the ability to follow the entire life spans of multiple RBC populations concurrently in the same subject, BioRBC offers distinct advantages for studying RBC biology and physiology, particularly RBC survival. The method for biotin labeling, validation of the method, and application of BioRBCs to studies of sickle cell disease, diabetes, and anemia of prematurity are reviewed. Studies documenting the safe use of BioRBC are reviewed; unanswered questions requiring future studies, remaining concerns, and regulatory barriers to broader application of BioRBC including adoption as a new reference method are also presented.
Biotin labeling as an alternative nonradioactive approach to determination of red cell survival. [2019]Biotin labeling of red cells was studied using different approaches to see if biotinylation is a useful label for determination of erythrocyte survival. Mouse red cells were labeled with biotin, either in vivo by injection or in vitro. In vivo labeled red cells were followed up in some mice without transfusing the labeled erythrocytes. Furthermore, in vivo labeled as well as in vitro labeled red cells were transfused into syngeneic mice. The biotin label allows an easy discrimination between labeled and unlabeled red cells during FACS analysis, and it is relatively stable for at least 50 days. All the three different approaches give similar results. Mean red cell life spans of in vivo or in vitro labeled red cells either transfused or followed up in vivo were between 44 and 52 days (T50 mean 23.9 days) when red cell destruction was assumed to be only a result of senescence. Mean red cell life spans were between 8 and 18 days (T50 mean 9.5 days) when a random destruction independent of red cell age was suggested. All the survival slopes are neither simple linear functions of time nor logarithmic functions, but they show an overlay of linear function by a logarithmic function where the components of both are unknown.
Direct in vivo biotinylation of erythrocytes as an assay for red cell survival studies. [2019]Direct in vivo labeling of erythrocytes with biotin is shown as a method for estimation of red cell survival as well as of enrichment of young or aged erythrocytes. Two succinimide esters (biotin-N-hydroxysuccinimide ester [BNHS], caproylamidobiotin-N-hydroxysuccinimide ester [C-BNHS] were used for biotin labeling of erythrocytes. With improved syntheses, pure BNHS (mp, 212 degrees-214 degrees C) and the spacered intermediate for C-BNHS, 6-(biotinylamide) hexanoate (mp, 225 degrees-226 degrees C) were obtained in an overall yield of 86%; the yield of C-BNHS (mp, 167 degrees-169 degrees C) was 68%. When three doses of 1 mg C-BNHS are injected intravenously into mice at 24-h intervals, all the red cells are biotin labeled. The rate of red cell production as well as the life span of red cells can be measured without any effect on erythropoiesis or damage by red cells in vitro. The survival curve seems to be linear, with 2.5%-3.3% disappearance of biotin-labeled red cells daily. In mice, in vivo biotin labeling avoids damaging red cells by in vitro procedures and does not influence the steady state of erythropoiesis by hypertransfusion. Therefore, in vivo biotin labeling is a very useful method for determining red cell survival time in small animals.
Time-dependent changes in the density and hemoglobin F content of biotin-labeled sickle cells. [2018]Sickle red blood cells (RBC) are subject to a number of important cellular changes and selection pressures. In this study, we validated a biotin RBC label by comparison to the standard 51Cr label, and used it to study changes that occur in sickle cells as they age. Sickle RBC had a much shorter lifespan than normal RBC, but the two labels gave equivalent results for each cell type. A variable number of sickle, but not normal, RBC disappeared from the circulation during the first few hours after reinfusion. The number of biotinylated sickle reticulocytes was decreased by 50% after 24 h and 75% after 48 h, with a gradual decrease in the amount of reticulum per cell. The labeled sickle cells exhibited major density increases during the first 4-6 d after reinfusion, with smaller changes thereafter. A small population of very light, labeled sickle RBC was essentially constant in number after the first few days. Fetal hemoglobin (HbF) content was determined in isolated biotinylated sickle RBC after reinfusion, allowing an estimate of lifespan for RBC containing HbF (F cells) and non-F cells. The lifespan of sickle biotinylated RBC lacking HbF was estimated to be approximately 2 wk, whereas F cells survived 6-8 wk.
Red blood cell (RBC) survival determined in humans using RBCs labeled at multiple biotin densities. [2021]Safe, accurate methods permitting simultaneous and/or repeated measurement of red blood cell (RBC) survival (RCS) are important to investigate pathophysiology and therapy of anemia. Methods using chromium 51 ((51) Cr)-labeled RBCs are unacceptable for infants, children, and pregnant women. We report RCS measured in vivo using RBCs labeled with several densities of biotin (BioRBCs).
Antibodies against biotin-labeled red blood cells can shorten posttransfusion survival. [2022]Label="BACKGROUND">In hematologic and transfusion medicine research, measurement of red blood cell (RBC) in vivo kinetics must be safe and accurate. Recent reports indicate use of biotin-labeled RBC (BioRBC) to determine red cell survival (RCS) offers substantial advantages over 51 Cr and other labeling methods. Occasional induction of BioRBC antibodies has been reported.
Current good manufacturing practices-compliant manufacture and measurement of biotin-labeled red blood cells. [2023]Red blood cells (RBCs) can be labeled with N-hydroxysuccinimidobiotin (sulfo-NHS-biotin), which binds to cell surface proteins under aqueous conditions. Biotinylated RBCs can be safely infused and detected in peripheral blood samples using flow cytometry, using a fluorochrome-conjugated streptavidin (SA) detection reagent. Biotinylated RBCs have been used to track survival of transfused RBCs, and have applications in optimizing RBC storage and in understanding donor genetic, environmental and disease factors affecting RBC products.