Determination of Red Cell Survival in Sickle Cell Disease and Other Hemoglobinopathies Using Biotin Labeling

NCT06313398 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: 10001883001883-H
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Sickle cell disease (SCD) is an inherited disorder of the blood. SCD causes red blood cells (RBCs) to die early. This can lead to a shortage of healthy cells. SCD and other blood disorders can be managed with drugs or cured with a bone marrow transplant. Researchers want to know how long RBCs survive in people with SCD and other blood disorders before and after treatment compared to those who had a bone marrow transplant. Objective: To learn how long RBCs survive in the body in people with SCD and other blood disorders compared to those whose disease was cured with a bone marrow transplant. Eligibility: People aged 18 years or older with SCD or another inherited blood disorder. People whose SCD or blood disorder was cured with a bone marrow transplant are also needed. Design: Participants will be screened. They will have a physical exam with blood and urine tests. Participants will have about 7 tablespoons of blood drawn. In the lab, this blood will be mixed with a vitamin called biotin. Biotin sticks to the outside of RBCs. This process is called "biotin labeling of RBCs." The next day, the participant s own biotin-labeled RBCs will be returned to their bloodstream. Participants will return regularly to have smaller blood samples (about 2 teaspoons) drawn. These samples will be tested to detect the percentage of cells that have biotin labels. These visits may be every 2 weeks, 4 weeks, or some other interval. Participants will continue this schedule for up to 20 weeks or until biotin can no longer be detected....

Conditions

Sickle Cell Disease; Thalassemia; Hemoglobinopathy

Keywords

Red Cell; Hemoglobinopathy; Thalassemia; Sickle Cell Disease; Biotin

Outcome Measures

Primary Outcomes (1)

• To determine and compare red blood cell survival, by virtue of the mean number of days of detectable biotin-labeled RBCs, in participants with SCD and/or other hemoglobinopathies.

  Enumeration of biotin-labeled RBCS (BioRBCs) will be performed by flow cytometry. F-cell and/or S-cell measurement will be done by flow cytometry. BioRBCs will be isolated from post-infusion blood samples using flow cytometry separation. The collected BioRBCs and the whole blood fraction will be analyzed by high performance liquid chromatography (HPLC) for hemoglobin content.

  Patients w/o transplant: lab draw every 2 weeks until biotin-labeled cells are no longer detected. Patients Post-transplant: lab draw every four weeks, until week 12. Lab draw every 2 weeks until biotin-labeled cells are no longer detected.

Secondary Outcomes (1)

• Validate the association of RBC survival with known markers of increased survival.

  Patients w/o transplant: lab draw every 2 weeks until biotin-labeled cells are no longer detected. Patients Post-transplant: lab draw every four weeks, until week 12. Lab draw every 2 weeks until biotin-labeled cells are no longer detected.

Study Arms (1)

RBC survival in patients with SCD

EXPERIMENTAL

RBC lifespan, determined by the mean number of days from biotin-labeled RBC infusion until biotin-labeled RBCs are below limit of detection, in patients with inherited hemoglobinopathies prior to and post initiation of disease modifying therapy or HSCT

Biological: Biotin-labeled red blood cells

Interventions

Biotin-labeled red blood cells BIOLOGICAL

Cellular Product (patient's own red blood cells washed in Biotin and infused back to patient)

RBC survival in patients with SCD

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 years or greater with confirmed diagnosis of SCD (all genotypes), thalassemia (beta and/or alpha), or other inherited hemoglobinopathy not otherwise specified.
• Be at steady state for their underlying disease (e.g. SCD or thalassemia) or post-bone marrow transplantation status, as evidenced by medical history.
• Ability to have blood samples drawn.
• For female participants of child-bearing potential, agree to use birth control during study participation. Female subjects of child-bearing potential must agree to use a medically acceptable method of birth control such as an oral contraceptive, intrauterine device, barrier and spermicide, or contraceptive implant/injection from start of screening through 4 months after infusion.
• Agreement to adhere to Lifestyle Considerations throughout study duration

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Consumption of biotin supplements or raw eggs within the last 30 days.
• Blood loss within the previous 8 weeks (\>540 mL).
• Red cell transfusion for their underlying SCD and/or thalassemia within the last 3 months.
• a. Participants may be eligible after three months following their last transfusion.
• Patients on hemodialysis, due to possibility of early removal of biotinylated RBCs.
• Pregnancy, lactation or absence of adequate contraception for fertile female subjects.
• Pediatric subjects will not participate in this study.
• Known allergic reactions to biotin, due to risk of possible life-threatening allergic reaction.
• Current diagnosis of malignancy (liquid and/or solid).

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• Children's National Research Institute: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Sickle Cell; Thalassemia; Hemoglobinopathies

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• John F Tisdale, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christina C Luckett

CONTACT

(301) 529-7863; christina.luckett@nih.gov

John F Tisdale, M.D.

CONTACT

(301) 402-6497; johntis@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2024
• First Posted: March 15, 2024
• Study Start: May 17, 2024
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): June 15, 2029
• Last Updated: February 24, 2026

Record last verified: 2026-02-20

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)