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

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ClinicalTrials.gov Identifier: NCT04476277
Recruitment Status : Recruiting
First Posted : July 20, 2020
Last Update Posted : April 22, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Tracking Information
First Submitted Date  ICMJE July 17, 2020
First Posted Date  ICMJE July 20, 2020
Last Update Posted Date April 22, 2021
Actual Study Start Date  ICMJE April 19, 2021
Estimated Primary Completion Date December 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2020)
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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Red Cell Half Life Determination in Patients With and Without Sickle Cell Disease
Official Title  ICMJE Red Cell Half Life Determination in Patients With and Without Sickle Cell Disease
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.

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Sickle Cell Disease
  • Sickle Cell Anemia
Intervention  ICMJE Drug: Biotin label
Autologous cells will be collected and biotin-labeled ex vivo and reinfused to measure red cell survival
Study Arms  ICMJE Experimental: 1
Autologous cells will be collected and biotin-labeled ex vivo and reinfused to measure red cell survival
Intervention: Drug: Biotin label
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 17, 2020)
21
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Wynona Coles (301) 402-2104 wcoles@nhlbi.nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04476277
Other Study ID Numbers  ICMJE 200080
20-H-0080
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
Study Sponsor  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: John F Tisdale, M.D. National Heart, Lung, and Blood Institute (NHLBI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date November 10, 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP