Red Blood Cell Survival Study for Sickle Cell Disease

No longer recruiting at 2 trial locations

Overseen By Marianne Yee, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Marianne Yee

Disqualifiers: Biotin, Raw egg supplements, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the lifespan of red blood cells (RBCs) in individuals with sickle cell disease who receive regular blood transfusions. Researchers will use a small amount of biotin-labeled RBCs (biotinylated red blood cells) during a participant's usual transfusion and track their survival over several months. Individuals with sickle cell disease or transfusion-dependent thalassemia who have received regular transfusions for at least three months may be suitable candidates. This study could enhance transfusion treatments for these conditions. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants a chance to contribute to groundbreaking medical insights.

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.

Is there any evidence suggesting that biotin labeled red blood cells are likely to be safe for humans?

Research has shown that labeling red blood cells (RBCs) with biotin is safe. Studies have used this method to determine the lifespan of RBCs in individuals with sickle cell disease (SCD). These studies found no serious side effects from using biotin-labeled RBCs. This technique effectively tracks RBC survival without harming patients.

This trial is in an early stage, focusing primarily on the treatment's safety for participants. The method's safe use in other studies suggests it is generally well-tolerated. However, as with any treatment, risks may still exist. This trial aims to provide more information about its safety in people with SCD. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for sickle cell disease focus on managing symptoms and preventing complications, often using medications like hydroxyurea or blood transfusions. However, researchers are excited about biotin-labeled red blood cells because they offer a unique way to study red blood cell survival and turnover. By tagging the red blood cells with biotin, doctors can track how long these cells last in the body, providing valuable insights into the effectiveness of transfusions and potentially leading to more tailored and effective treatment strategies. This approach is different from standard treatments as it focuses on understanding the disease process at a cellular level rather than just alleviating symptoms.

What evidence suggests that biotin labeled red blood cells are effective for measuring red blood cell survival in sickle cell disease?

Research has shown that marking red blood cells (RBCs) with biotin effectively tracks their lifespan after transfusion in patients with sickle cell disease (SCD). In this trial, participants will receive a transfusion with biotin-labeled RBCs to directly measure the survival of these transfused RBCs over time. This method has been safely used in SCD patients to study the lifespan of these cells. Understanding RBC longevity can help evaluate the effectiveness of transfusions in managing SCD complications, as the lifespan of transfused RBCs can vary significantly in these patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Marianne Yee, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Biotin Labeled Red Blood Cells

Trial Overview 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.

How Is the Trial Designed?

Group I: Biotin labeled Red Blood Cells Experimental Treatment 2 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

Who Is Running the Clinical Trial?

Marianne Yee

Lead Sponsor

Trials

1

Recruited

40+

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Cerus Corporation

Industry Sponsor

Trials

20

Recruited

4,800+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Biotin labeling of red blood cells, whether done in vivo or in vitro, proved to be an effective method for tracking erythrocyte survival, with a stable label lasting at least 50 days.

The study found that the average lifespan of red blood cells was between 44 and 52 days under normal conditions, but could drop to 8 to 18 days when considering random destruction, indicating that factors beyond aging can affect red cell survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biotin labeling as an alternative nonradioactive approach to determination of red cell survival. Hoffmann-Fezer, G., Mysliwietz, J., Mörtlbauer, W., et al.[2019]

A new method using biotin-labeled red blood cells (BioRBCs) allows for safe and accurate measurement of red blood cell survival in vivo, which is particularly beneficial for infants, children, and pregnant women who cannot use traditional chromium-51 methods.

This biotin labeling technique enables multiple independent measurements of red blood cell survival without exposing subjects to radiation and requires only small blood volumes, making it a significant advancement in studying anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Red blood cell (RBC) survival determined in humans using RBCs labeled at multiple biotin densities. Mock, DM., Matthews, NI., Zhu, S., et al.[2021]

The biotin labeling method for red blood cells (BioRBC) is a straightforward and robust technique that allows researchers to track the lifespan and properties of multiple RBC populations in the same subject, offering advantages over the traditional (51)Cr RBC labeling method.

BioRBC has been shown to be safe and effective for studying various conditions such as sickle cell disease, diabetes, and anemia of prematurity, although there are still unanswered questions and regulatory challenges that need to be addressed for broader application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of posttransfusion red cell survival with the biotin label. Mock, DM., Widness, JA., Veng-Pedersen, P., et al.[2021]

Re-exposure to biotin-labeled red blood cells (BioRBC) in previously immunized adults led to an increase in specific antibodies, which can affect the accuracy of red cell survival measurements.

No adverse clinical events were reported during the study, but to reduce the risk of antibody induction and ensure accurate red cell survival assessments, it is recommended to limit the initial BioRBC exposure volume to ≤10 mL and use label densities of ≤18 μg/mL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibodies against biotin-labeled red blood cells can shorten posttransfusion survival. Mock, DM., Stowell, SR., Franco, RS., et al.[2022]

In a study of 10 patients with sickle cell disease, it was found that red blood cells (RBCs) containing fetal hemoglobin (HbF) survived longer than those without, indicating that higher HbF levels contribute to improved RBC longevity.

The survival of non-fetal hemoglobin (non-F) cells was inversely related to the percentage of F cells, with patients having more F cells experiencing significantly longer RBC survival times, suggesting that increasing HbF through treatments like hydroxyurea could enhance overall RBC lifespan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of fetal hemoglobin on the survival characteristics of sickle cells. Franco, RS., Yasin, Z., Palascak, MB., et al.[2021]

Sickle red blood cells (RBC) have a significantly shorter lifespan compared to normal RBC, with biotin labeling showing that sickle RBC without fetal hemoglobin (HbF) survive for about 2 weeks, while those with HbF can last 6-8 weeks.

The study validated a biotin RBC label against the standard 51Cr label, confirming that both methods yield equivalent results, and revealed that sickle RBCs experience rapid loss from circulation shortly after reinfusion, particularly in reticulocytes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-dependent changes in the density and hemoglobin F content of biotin-labeled sickle cells. Franco, RS., Lohmann, J., Silberstein, EB., et al.[2018]

In vivo biotin labeling of erythrocytes using biotin-N-hydroxysuccinimide ester (BNHS) and caproylamidobiotin-N-hydroxysuccinimide ester (C-BNHS) allows for accurate estimation of red blood cell survival without damaging the cells or affecting their production.

This method demonstrated a consistent daily disappearance rate of biotin-labeled red cells (2.5%-3.3%), making it a reliable technique for studying red cell lifespan in small animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct in vivo biotinylation of erythrocytes as an assay for red cell survival studies. Hoffmann-Fezer, G., Maschke, H., Zeitler, HJ., et al.[2019]

A new closed-system procedure for biotinylating red blood cells (RBCs) has been developed, ensuring safety and compliance with current good manufacturing practices (cGMP), which is crucial for clinical applications.

Biotinylated RBCs can be reliably tracked in the bloodstream using flow cytometry, demonstrating stability for up to 50 days, which is important for optimizing RBC storage and understanding factors affecting transfusion outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current good manufacturing practices-compliant manufacture and measurement of biotin-labeled red blood cells. Donnenberg, AD., Kanias, T., Triulzi, DJ., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11088511/

Post-transfusion biotin-labeled red blood cell survival ... Biotin-labeling provides a direct measurement of red cell survival (RCS) over time, thus can be used to assess the clinical significance of RBC antibodies.

2. ashpublications.org ashpublications.org/bloodadvances/article/8/7/1806/506967/In-vivo-measurement-of-RBC-survival-in-patients

In vivo measurement of RBC survival in patients with sickle ... Biotin labeling of RBCs is a safe and feasible methodology to evaluate RBC survival in patients with SCD before and after HSCT.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04426591

Red Blood Cell Survival in Sickle Cell Disease Survival of the transfused biotin labeled RBCs will be assessed as the count of biotinylated RBCs per sample. Day 1, Weeks 1-12. Half-life of Biotinylated RBCs ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924000193

In vivo measurement of RBC survival in patients with sickle ... This study used biotin labeling of RBCs to determine the lifespan of RBCs in patients with SCD compared with patients who have successfully undergone curative ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4122272/

Measurement of Post-Transfusion Red Cell Survival with ... Over approximately the first two weeks in circulation, about one-third of the biotin labels per RBC are lost [53]. Based on studies conducted with isolated pure ...

6. redcrossplus.blog redcrossplus.blog/2025/02/13/biotin-labeled-red-cell-survival-in-pediatric-patients-with-sickle-cell-disease-who-form-antibodies-of-uncertain-clinical-significance/

Biotin-labeled red cell survival in pediatric patients with sickle ... Post-transfusion biotin-labeled red blood cell survival studies in pediatric sickle cell disease with antibodies of uncertain significance.