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

NCT04476277 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: 20008020-H-0080
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease; Sickle Cell Anemia

Keywords

Red Cell Survival; Biotin; Sickle Cell Anemia; Sickle Cell Disease; Sickle Cell Trait

Outcome Measures

Primary Outcomes (1)

• Mean Red Blood Cells Lifespan in Participants

  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.

  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.

Secondary Outcomes (13)

• Number of Participants With Antibody Detection

  Baseline, 3 months, 6 months

• Mean White Blood Cell Count

  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 Count

  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 Value

  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 Value

  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.

Study Arms (4)

Sickle Cell Disease Pre-Transplantation

EXPERIMENTAL

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

Sickle Cell Disease Post-Transplantation

EXPERIMENTAL

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

Sickle Cell Trait (HbAS)

EXPERIMENTAL

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

HbAA (Healthy volunteers)

EXPERIMENTAL

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

Interventions

Biotin label DRUG

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

HbAA (Healthy volunteers); Sickle Cell Disease Post-Transplantation; Sickle Cell Disease Pre-Transplantation; Sickle Cell Trait (HbAS)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Leonard AK, Furstenau D, Inam Z, Luckett C, Chu R, Demirci S, Essawi K, Gudmundsdottir B, Hinds M, DiNicola J, Li Q, Eaton WA, Cellmer T, Wang X, Thein SL, Macari ER, VanNest S, Hsieh MM, Bonner M, Pierciey FJ, Tisdale JF. In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation. Blood Adv. 2024 Apr 9;8(7):1806-1816. doi: 10.1182/bloodadvances.2023011397.

  PMID: 38181784 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Sickle Cell; Sickle Cell Trait

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Mathew Hsieh, M.D.
• Organization: National Heart, Lung, and Blood Institute (NHLBI)

matthewhs@nhlbi.nih.gov

301.402.7687

Study Officials

• John F Tisdale, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 20, 2020
• Study Start: April 19, 2021
• Primary Completion: December 20, 2022
• Study Completion: February 14, 2023
• Last Updated: February 13, 2024
• Results First Posted: February 13, 2024

Record last verified: 2023-02

Locations

US (1)