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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04476277
Recruitment Status : Not yet recruiting
First Posted : July 20, 2020
Last Update Posted : August 12, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

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:
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, 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: N/A
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
Estimated Study Start Date : August 17, 2020
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Biotin

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




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



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 to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Age 18 or greater with a confirmed diagnosis of homozygous sickle cell anemia (HbSS), sickle cell trait (HbAS), or ethnic-matched healthy volunteer (HbA).
  • Normal renal function: creatinine <1.5 mg/dL, proteinuria <1+.
  • Negative direct antiglobulin test (DAT).
  • Ability to give informed consent to participate in the protocol.

EXCLUSION CRITERIA:

  • Any active chronic illness other than sickle cell disease.
  • Blood transfusion within the preceding 90 days
  • Active viral, bacterial, fungal, or parasitic infection.
  • Consumption of biotin supplements or raw eggs within 30 days.
  • Blood loss within the previous 8 weeks >30mL including but not limited by blood donation, trauma, gastrointestinal bleeding.
  • Pregnancy
  • Pre-existing, naturally occurring antibodies against biotin

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


Contacts
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Contact: Stephanie N Helwing, R.N. (301) 827-0448 stephanie.helwing@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
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)
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: August 12, 2020
Last Verified: July 14, 2020

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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
Nutrients
Growth Substances
Physiological Effects of Drugs