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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04476277
Recruitment Status : Completed
First Posted : July 20, 2020
Last Update Posted : April 4, 2023
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Study Description
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Brief 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.


Condition or disease Intervention/treatment Phase
Sickle Cell Disease Sickle Cell Anemia Drug: Biotin label Early Phase 1

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 create a mathematical model incorporating RBC survival and reticulocyte count to determine the necessary amount of normal hemoglobin, and therefore vector copy number or amount of transferred globin, required for gene therapy protocols.

Endpoints:

Primary Endpoint: Red blood cell survival

Secondary Endpoints: Relationship of red blood cell survival to hematologic parameters. Antibody detection to biotin.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Red Cell Half Life Determination in Patients With and Without Sickle Cell Disease
Actual Study Start Date : April 19, 2021
Actual Primary Completion Date : December 20, 2022
Actual Study Completion Date : February 14, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Biotin

Arms and Interventions
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Arm Intervention/treatment
Experimental: Sickle Cell Disease Pre-Transplantation
Autologous cells will be collected in participants with Sickle Cell Disease Pre-Transplantation and biotin-labeled ex vivo and reinfused to measure red cell survival
 Drug: Biotin label
Autologous cells will be collected and biotin-labeled ex vivo and reinfused to measure red cell survival
Experimental: Sickle Cell Disease Post-Transplantation
Autologous cells will be collected in participants with Sickle Cell Disease Post-Transplantation and biotin-labeled ex vivo and reinfused to measure red cell survival
 Drug: Biotin label
Autologous cells will be collected and biotin-labeled ex vivo and reinfused to measure red cell survival
Experimental: Sickle Cell Trait (HbAS)
Autologous cells will be collected in participants with Sickle Cell Trait (HbAS) and biotin-labeled ex vivo and reinfused to measure red cell survival
 Drug: Biotin label
Autologous cells will be collected and biotin-labeled ex vivo and reinfused to measure red cell survival
Experimental: HbAA (Healthy volunteers)
Autologous cells will be collected in participants with HbAA (Healthy volunteers) and biotin-labeled ex vivo and reinfused to measure red cell survival
 Drug: Biotin label
Autologous cells will be collected and biotin-labeled ex vivo and reinfused to measure red cell survival


Outcome Measures
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Primary Outcome Measures :
  1. To determine and compare red blood cell survival in patients with SCD (HbSS genotype), patients with SCD who have undergone BMT, subjects with SCT, and healthy donors [ Time Frame: 6 months ]
    Percentage of red blood cells at specific time points as measured by flow cytometry.


Secondary Outcome Measures :
  1. To create a mathematical model incorporating RBC survival and reticulocyte count to determine the necessary amount of normal hemoglobin, and therefore VCN, required for gene therapy protocols [ Time Frame: 18 months ]
    Design completion of mathematical model


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04476277


Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: John F Tisdale, M.D. National Heart, Lung, and Blood Institute (NHLBI)
More Information
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Additional Information:

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Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT04476277    
Other Study ID Numbers: 200080
20-H-0080
First Posted: July 20, 2020    Key Record Dates
Last Update Posted: April 4, 2023
Last Verified: February 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Red Cell Survival
Biotin
Sickle Cell Anemia
Sickle Cell Disease
Sickle Cell Trait
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
 Genetic Diseases, Inborn
Biotin
Vitamin B Complex
Vitamins
Micronutrients
Physiological Effects of Drugs