Red Cell Half Life Determination in Patients With and Without Sickle Cell Disease
Study Details
Study Description
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 |
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|
Early Phase 1 |
Detailed Description
The mean potential lifespan (MPL) of RBCs can be quantified by either a population or cohort study. Such studies have corroborated the MPL of healthy donor (HD) RBCs to be approximately 115 days while RBCs from subjects with sickle cell disease (SCD) have a much more variable but consistently shorter MPL of approximately 32 days. Allogeneic hematopoietic stem cell transplant (HSCT) is utilized as a curative therapy for the treatment of severe SCD resulting in, among other pathophysiological advantages, restoration of a HD RBC phenotype. This study will evaluate the population methodology (biotin-labeled RBCs) to determine MPL in subjects with SCD compared to patients who have successfully undergone allogeneic BMT (allogeneic or autologous), subjects with sickle cell trait, and healthy donors without 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 1 Autologous cells will be collected 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
Primary Outcome Measures
- 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 [6 months]
Percentage of red blood cells at specific time points as measured by flow cytometry.
Secondary Outcome Measures
- 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 [18 months]
Design completion of mathematical model
Eligibility Criteria
Criteria
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INCLUSION CRITERIA:
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Age 18 or greater with a confirmed diagnosis of homozygous SCD (HbSS, HbSC, HbSB0), sickle cell trait (HbAS), or healthy volunteer (HbA)
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Normal renal function: creatinine <1.5 mg/dL
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Negative direct antiglobulin test (DAT)
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Ability to give informed consent to participate in the protocol
EXCLUSION CRITERIA:
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Any uncontrolled chronic illness other than sickle cell disease
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Active viral, bacterial, fungal, or parasitic infection
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Consumption of biotin supplements or raw eggs within 30 days
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Blood loss within the previous 8 weeks >540mL
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Pregnancy
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Pre-existing, naturally occurring antibodies against biotin
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | National Institutes of Health Clinical Center | Bethesda | Maryland | United States | 20892 |
Sponsors and Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
Investigators
- Principal Investigator: John F Tisdale, M.D., National Heart, Lung, and Blood Institute (NHLBI)
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 200080
- 20-H-0080