Skip to main content
OpenTrials
Completed

NCT Number: NCT04476277

Red Cell Half Life Determination in Patients With and Without Sickle Cell Disease

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Sickle Cell Anemia Sickle Cell Trait

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18 or greater with a confirmed diagnosis of homozygous SCD (HbSS, HbSC, HbSB0), sickle cell trait (HbAS), or healthy volunteer (HbA)
  • Normal renal function: creatinine <1.5 mg/dL
  • Negative direct antiglobulin test (DAT)
  • Ability to give informed consent to participate in the protocol

Exclusion criteria

  • Any uncontrolled chronic illness other than sickle cell disease
  • Active viral, bacterial, fungal, or parasitic infection
  • Consumption of biotin supplements or raw eggs within 30 days
  • Blood loss within the previous 8 weeks >540mL
  • Pregnancy
  • Pre-existing, naturally occurring antibodies against biotin

Treatment and study plan

Biotin label

Drug

Autologous cells will be collected and biotin-labeled ex vivo and reinfused to measure red cell survival

Primary outcomes

  1. Mean Red Blood Cells Lifespan in Participants

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Days of Red Blood Cells (RBC) survival in participants with Sickle Cell Disease (SCD), participants with SCD who have undergone stem cell transplant, participants with Sickle Cell Trait, and healthy volunteers.

    Peripheral blood samples were analyzed by flow cytometry until biotin was not detectable on RBC.

Secondary outcomes

  1. Number of Participants With Antibody Detection

    Time frame: Baseline, 3 months, 6 months

    Number of participants with Antibody detection to biotin

  2. Mean White Blood Cell Count

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean White Blood Cell (WBC) count between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  3. Mean Red Blood Cell Count

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Red Blood Cell (RBC) Count between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  4. Mean Hemoglobin Value

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Hemoglobin (Hb) Value between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  5. Mean Hematocrit Value

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Hematocrit (Hct) value between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  6. Mean Value of Mean Corpuscular Volume

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Value of Mean Corpuscular Volume (MCV) between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  7. Mean Absolute Reticulocyte Count

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Absolute Reticulocyte Count (ARC) between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  8. Mean Aspartate Aminotransferase Value

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Aspartate Aminotransferase (AST) value between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  9. Mean Total Bilirubin Value

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Total Bilirubin value between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  10. Mean Lactate Dehydrogenase Value

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Lactate Dehydrogenase (LDH) value between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  11. Mean Adult Hemoglobin Percentage

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Adult Hemoglobin (HbA) percentage between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  12. Mean Sickle Hemoglobin Percentage

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Sickle Hemoglobin (HbS) Percentage between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

  13. Mean Fetal Hemoglobin Percentage

    Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.

    Mean Fetal Hemoglobin (HbF) Percentage between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation

Sponsors and collaborators

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Nih

Registry information

Important dates

Study start
2021
Primary completion
2022
Study completion
2023
First posted
Jul 20, 2020
Registry last updated
Feb 13, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.