Red Blood Cell Survival Study for Sickle Cell Disease

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

40 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{2 4 5 6 7}

How 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. ^{2 3 4 5 8}

Research Team

Marianne Yee, MD

Principal Investigator

Emory University

Eligibility 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.

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The effect of fetal hemoglobin on the survival characteristics of sickle cells. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Measurement of posttransfusion red cell survival with the biotin label. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Biotin labeling as an alternative nonradioactive approach to determination of red cell survival. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Direct in vivo biotinylation of erythrocytes as an assay for red cell survival studies. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Time-dependent changes in the density and hemoglobin F content of biotin-labeled sickle cells. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Red blood cell (RBC) survival determined in humans using RBCs labeled at multiple biotin densities. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Antibodies against biotin-labeled red blood cells can shorten posttransfusion survival. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Current good manufacturing practices-compliant manufacture and measurement of biotin-labeled red blood cells. [2023]