Red Cell Half Life Determination in Patients With and Without Sickle Cell Disease
Condition: Sickle Cell Disease; Sickle Cell Anemia
MeSH terms: Anemia, Sickle Cell
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Background:

      Sickle cell disease (SCD) is an inherited blood disorder. It results from a single genetic
      change (mutation) in red blood cells (RBCs). RBCs are the cells that carry oxygen to the
      body. In people with SCD, some RBCs are abnormal and die early. This leaves a shortage of
      healthy RBCs. Researchers want to learn more about how long RBCs live in the human body.

      Objective:

      To study how long RBCs live in people with and without SCD.

      Eligibility:

      People age 18 and older who either have SCD, had SCD but were cured with a bone marrow
      transplant, have the sickle cell trait (SCT), or are a healthy volunteer without SCD or SCT

      Design:

      Participants will be screened with a medical history and physical exam. They will give a
      blood sample.

      Participants will have a small amount of blood drawn from a vein. In the laboratory, the
      blood will be mixed with a vitamin called biotin. Biotin sticks to the outside of RBCs
      without changing their function, shape, or overall lifetime. This process is known as biotin
      labeling of RBCs. The biotin labeled RBCs will be returned to the participant via vein
      injection.

      Participants will give frequent blood samples. Their RBCs will be studied to see how many
      biotin labeled RBCs remain over time. This shows how long the RBCs live. Participants will
      give blood samples until no biotin labeled RBCs can be detected.

      During the study visits, participants will report any major changes to their health.

      Participation lasts for up to 6 months.
    

Detailed description: 
      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) compared to patients who
      have successfully undergone curative bone marrow transplantation (BMT, allogeneic or
      autologous), participants with sickle cell trait, and healthy donors without SCD. Previous
      studies have corroborated the MPL of healthy donor RBCs to be approximately 115 days while
      RBCs from patients with SCD have a much more variable but consistently shorter MPL of
      approximately 32 days. Allogeneic BMT is a curative therapy for the treatment of severe SCD
      with stable, mixed donor recipient chimerism after BMT sufficient to reverse the sickle cell
      phenotype by virtue of improved donor red cell survival compared to the ineffective
      erythropoiesis of SCD. We predict that the hematologic variables associated with red cell
      survival among patients with SCD vs. participants with SCT and healthy donors can be used to
      determine the necessary amount of corrected hemoglobin required to overcome the red cell
      pathology of SCD. Data generated will be used to determine the utility of performing a
      population study of RBC lifespan in gene therapy treated patients to ultimately target the
      percentage of transferred globin gene needed to reverse SCD. The data generated will refine
      our understanding of the degree of correction necessary to reverse the phenotype of SCD.

      Objectives:

      Primary Objective: To determine and compare red blood cell survival in patients with SCD,
      patients with SCD who have undergone BMT, participants with SCT, and healthy donors, and
      validate the association of red cell survival with known markers of increased red cell
      survival.

      Secondary Objectives: To evaluate correlation of markers of hemolysis (reticulocyte count),
      number of alpha globin genes, and fetal hemoglobin with RBC survival.

      Endpoints:

      Primary Endpoint: Red blood cell survival

      Secondary Endpoints: Relationship of red blood cell survival to hematologic parameters.
      Antibody detection to biotin.
    

Intervention name(s): Biotin label
Intervention type(s): Drug
Intervention description(s): Autologous cells will be collected and biotin-labeled ex vivo and reinfused to measure red cell survival
Intervention MeSH terms: Biotin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Red Cell Survival; Biotin; Sickle Cell Anemia; Sickle Cell Disease; Sickle Cell Trait