Red Blood Cell Survival in Sickle Cell Disease

Last updated: December 20, 2024
Sponsor: Marianne Yee
Overall Status: Active - Recruiting

Phase

1

Condition

Sickle Cell Disease

Red Blood Cell Disorders

Treatment

INTERCEPT Blood System

Biotin Labeled Red Blood Cells

Clinical Study ID

NCT04426591
IRB00117580
1K23HL146904
  • Ages 2-65
  • All Genders

Study Summary

This is a single-arm, mechanistic clinical trial to measure predictors of senescence and the in vivo survival of transfused red blood cells (RBCs) in individuals with sickle cell disease (SCD) receiving chronic transfusion therapy (CTT). Chronic transfusion in patients with SCD is a common treatment. The efficacy of RBC transfusion therapy to treat or prevent complications of SCD may be hampered by variable survival of the transfused donor RBC. The overall aim is to see how long RBC survive in SCD patients who are chronically transfused. When a study participant has a regular blood transfusion the researchers will label a small portion of the RBCs that are transfused with biotin. The participant will return at Day 1, weekly for 3 months and monthly for 3 months to measure how long those RBCs survive. An optional sub-study using INTERCEPT RBCs will mirror the main study but will use INTERCEPT RBCs that have biotinylated for 1 RBC unit.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Hemoglobinopathy:

  • Any sickle cell disease genotype, or

  • Transfusion-dependent thalassemia (TDT)

  • Receiving CTT for ≥3 months prior to enrollment.

  • For participants with past BioRBC transfusion exposure, BioRBC antibody screens musthave been conducted through at least 6 months post exposure, with negative results.

Exclusion

Exclusion Criteria:

  • Anticipated cessation of CTT in the next ≤2 months

  • Ongoing consumption of biotin or raw egg dietary supplements

  • Antibody specific of INTERCEPT RBCs at baseline (for subjects consenting to theoptional arm)

  • BioRBC-specific antibodies ever detected in the past, or detected on post-enrollmentscreening prior to first infusion of Bio-RBC.

Study Design

Total Participants: 40
Treatment Group(s): 2
Primary Treatment: INTERCEPT Blood System
Phase: 1
Study Start date:
October 29, 2021
Estimated Completion Date:
May 31, 2025

Study Description

Sickle cell disease (SCD) carries significant morbidity as a result of red blood cell (RBC) sickling and hemolysis. Stroke is one of the most devastating sequelae of SCD. Chronic transfusion therapy (CTT) reduces stroke risk by supplying normal, non-sickle RBC to circulation, thereby reducing the percentage of endogenous sickle RBC in circulation, and maintaining a higher hemoglobin (Hb), thereby suppressing erythropoiesis of new sickle RBC. While the efficacy of CTT in stroke prophylaxis is well-established, nearly 45% of children continue to have silent or overt strokes despite CTT. The failure of CTT to prevent stroke events may be related to inadequate reduction of circulating sickle RBC and erythropoiesis. The amount of circulating sickle-RBC is related to the survival kinetics of both transfused RBC and endogenous sickle RBC.

In a large, longitudinal analysis of CTT in SCD, the researchers found wide variation in the survival of donor RBC following transfusion, with faster clearance associated with patient immune features (historical RBC alloimmunization and spleen presence) and with donor RBC glucose-6-phosphate-dehydrogenase (G6PD) deficiency. To better understand the roles of patient and donor factors in the survival and clearance of transfused RBC, the researchers propose a mechanistic, clinical trial during chronic transfusion episodes in patients with SCD, in which a small aliquot of each transfused unit is labeled with biotin conjugated to RBC surface proteins, to safely identify and measure the in vivo survival of donor RBC.

Aim 1 will examine the relationships of the recipient's immune system (past alloimmunization, splenic volume, and markers of reticuloendothelial system function) on the post-transfusion survival of biotin-labeled donor RBC.

Aim 2 will examine the relationships of donor RBC G6PD levels and donor RBC metabolomics with the in vivo survival and changes in donor RBC senescence markers. Completion of these aims will increase the understanding of mechanisms for the variability in RBC survival during CTT, identifying donor and recipient risk factors for decreased RBC survival. Ultimately this knowledge will inform the management of CTT to improve the prevention of strokes in SCD.

Aim 3 will compare the in vivo survival and clearance rate of phenotype-matched RBCs prepared with an investigational pathogen-reduction system (INTERCEPT Blood System) vs. the in vivo survival and clearance rate of conventional, phenotype-matched RBCs (not treated with INTERCEPT). Biotin labeling of donor RBC will be used to measure RBC survival. This is an optional study activity for study participants.

Connect with a study center

  • Childrens Healthcare of Atlanta

    Atlanta, Georgia 30322
    United States

    Active - Recruiting

  • Grady Health System

    Atlanta, Georgia 30322
    United States

    Active - Recruiting

  • Hughes Spalding Children's Hospital

    Atlanta, Georgia 30303
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.