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Red Blood Cell Survival in 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: NCT04426591
Recruitment Status : Recruiting
First Posted : June 11, 2020
Last Update Posted : November 3, 2021
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
John D Roback, Emory University

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Biotin Labeled Red Blood Cells Phase 1

Detailed 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 (1) supplying normal, non-sickle RBC to circulation, thereby reducing the percentage of endogenous sickle RBC in circulation, and (2) 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Kinetics of Donor Red Blood Cell Survival in Sickle Cell Disease
Actual Study Start Date : October 29, 2021
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : May 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Biotin

Arms and Interventions
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Arm Intervention/treatment
Experimental: Biotin labeled Red Blood Cells
Participants receiving a transfusion with biotin labeled RBCs. Samples will be taken for 12 weeks after the biotinylated transfusion. During this time participants will continue to receive regular monthly transfusions (non-biotinylated) as part of CTT.
 Drug: Biotin Labeled Red Blood Cells
On the day of transfusion, a 20 mL aliquot will be sterilely withdrawn from each RBC unit, washed and labeled with sulfo-NHS-biotin for 30 minutes, washed to stop the labeling reaction, then resuspended in plasma to a hematocrit of ~60%. The biotin-labeled RBC (BioRBC) will be transfused along with the remainder of the RBC unit (unlabeled volume). Standard blood bank and CTT protocols and minor antigen matching for SCD patients will be followed. Exact transfusion volume will be determined based on pre-transfusion Hb, HbS, and body weight, per clinical protocol.


Outcome Measures
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Primary Outcome Measures :
  1. Change in Number of Biotin Labeled RBCs [ Time Frame: Day 1, Weeks 1-12 ]
    Survival of the transfused biotin labeled RBCs will be assessed as the count of biotinylated RBCs per sample.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HbSS or HbSβ0 thalassemia SCD
  • receiving CTT for ≥3 months prior to enrollment

Exclusion Criteria:

  • anticipated cessation of CTT in the next ≤2 months
  • concurrent hydroxyurea therapy
  • automated RBC exchange therapy within 3 months prior to enrollment or anticipated within the next 3 months
  • delayed hemolytic transfusion reaction in the past 3 months
  • consuming high-dose biotin or raw egg supplements
  • current pregnancy
Contacts and Locations
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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): NCT04426591


Contacts
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Contact: Marianne Yee, MD 404-785-6190 Marianne.Yee@choa.org

Locations
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United States, Georgia
Hughes Spalding Children's Hospital Recruiting
Atlanta, Georgia, United States, 30303
Childrens Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30322
Grady Health System Recruiting
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Marianne Yee, MD Emory University
More Information
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Responsible Party: John D Roback, Professor, Emory University
ClinicalTrials.gov Identifier: NCT04426591    
Other Study ID Numbers: IRB00117580
1K23HL146904 ( U.S. NIH Grant/Contract )
First Posted: June 11, 2020    Key Record Dates
Last Update Posted: November 3, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All of the individual participant data collected during the trial will be made available for sharing with other researchers, after deidentification.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Individual participant data will be made available for sharing immediately following publication, with no end date.
Access Criteria: Data will be available for sharing with researchers who provide a methodologically sound proposal, for the purpose of achieving the aims in the approved proposal. Proposals should be directed to Marianne.Yee@choa.org. To gain access, data requestors will need to sign a data access agreement.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
 Genetic Diseases, Inborn
Biotin
Vitamin B Complex
Vitamins
Micronutrients
Physiological Effects of Drugs