An Early Phase 1 interventional study of Biotin-labeled red blood cells in Sickle Cell Disease, Thalassemia and Hemoglobinopathy, sponsored by National Heart, Lung, and Blood Institute (NHLBI). Recruiting at 1 site in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Early Phase 1, Interventional, and Other
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....
Study Description:
This study will use biotin-labeling of red blood cells (RBCs) to determine the mean potential lifespan (MPL) of RBCs in patients with sickle cell disease (SCD) and other hemoglobinopathies (e.g. thalassemia), including in those receiving disease modifying therapies or who have undergone curative hematopoietic stem cell transplantation (HSCT: allogeneic or autologous). Previous studies have corroborated the MPL of healthy donor RBCs to be approximately 115 days, while RBCs from patients with SCD have a more variable but consistently shorter MPL of approximately 32 days. We recently validated these findings and demonstrated the feasibility, safety, and efficacy of determining MPL of biotin-labeled RBCs in patients with SCD before and after transplant, persons with sickle cell trait, and healthy donors. Allogeneic HSCT is a curative treatment for severe SCD with stable, mixed donor-recipient chimerism after HSCT sufficient to reverse the sickle cell phenotype by virtue of improved donor red cell survival compared to the ineffective erythropoiesis of SCD. HSCT, both allogeneic and autologous, are also curative for certain hemoglobinopathies, such as transfusion dependent beta thalassemia (TDT), with donor cells able to overcome the ineffective erythropoiesis in TDT as well. We predict that the hematologic variables associated with red cell survival among patients with SCD and other hemoglobinopathies vary between individuals and are affected by disease modifying therapy, including curative therapies. The data generated will refine our understanding of the degree of correction necessary to reverse the clinical phenotype of SCD and other hemoglobinopathies, including that needed for autologous gene therapy to be curative.
Objectives:
Primary Objective:
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 before and after initiation of disease modifying therapy, including those who have undergone HSCT.
Secondary Objective:
To validate the association of red cell survival with known markers of increased survival, specifically absolute reticulocyte count, hemoglobin F or hemoglobin A percentage, and alpha globin mutation status (SCD participants only).
Exploratory Objective:
To create and pilot a mathematical model incorporating RBC survival and reticulocyte count to determine the necessary amount of normal hemoglobin or hemoglobin F needed to reverse sickle cell complications. Information from participants with inherited high HbF will be used.
Endpoints:
Primary Endpoint:
Red blood cell survival via measurement of detectable biotin-labeled RBC with time
Secondary Endpoint:
Relationship of RBC survival to hematologic parameters.
Exploratory Endpoint:
Amount of normal hemoglobin or hemoglobin F needed to reverse the sickle cell complications.
1,134 studies on the registry are indexed under Anemia, Sickle Cell; 238 are open to participants now.
This study's planned enrollment of 100 is above the median of 40 across 769 interventional studies indexed under Anemia, Sickle Cell.
Browse Anemia, Sickle Cell studies →National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,143 studies on the registry; 71 are open to participants now.
Of its 58 completed or terminated interventional studies of FDA-regulated products, 51 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Cellular Product (patient's own red blood cells washed in Biotin and infused back to patient)
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.
Time frame: 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.
Validate the association of RBC survival with known markers of increased survival.
We will measure the relationship of RBC survival to hematologic parameters known to be associated with survival, specifically hemolysis markers (e.g. absolute reticulocyte count, lactate dehydrogenase, total bilirubin, and aspartate aminotransferase), hemoglobin F or hemoglobin A percentage, and alpha globin gene mutation status obtained at baseline and during scheduled lab draws (except for alpha globin gene mutation analysis which is only done at baseline).
Time frame: 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.
Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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