The Impact of Oxidative Stress on Erythrocyte Biology (RBC Survival)

Red Blood Cell Survival Study: The Impact of Oxidative Stress on Erythrocyte Biology

This study will address if red blood cells transfused to a sickle cell patient from a donor with a glucose-6-phosphate-dehydrogenase (G6PD) enzyme deficiency have a different lifespan as measured by the percentage of red blood cells that survive post-transfusion compared to red blood cells transfused to a sickle cell patient from a donor without a G6PD enzyme deficiency.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease Without Crisis
• Intervention / Treatment: Biological: G6PD Deficient Red Blood Cell Transfusion; Biological: Non-G6PD deficient Red Blood Cell Transfusion

Detailed Description

This prospective, phase II, crossover, single-blind, randomized transfusion order study will address if red blood cells from donors with a G6PD enzyme deficiency have a different lifespan once transfused into a patient with sickle cell disease than red blood cells from an otherwise normal donor. Results of this critical study will guide future research and donor testing policies to ensure that patients receive the most appropriate units of blood for their condition. Each patient randomized to the study will receive 2 blood transfusions, one from a G6PD deficient donor and one from an otherwise normal donor. Half the patients (8) will receive G6PD deficient blood first while the other half (8) will receive non-G6PD deficient blood first. Patients will have a wash-out period of at least 4 months before receiving the opposite type of blood transfusion. The blood transfusion order will be randomized. There is currently no standard of testing in place to screen blood donations for G6PD enzyme deficiency. It is believed that up to 10% of the antigen-matched donors for patients with sickle cell disease are G6PD deficient, and the lifespan is unknown in the sickle cell population.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Wichlan; Phone Number: 919-966-6876; Email: david_wichlan@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Contact: David Wichlan; Phone Number: 919-966-6876; Email: david_wichlan@med.unc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-60 years
• Has diagnosis of sickle cell disease
• Steady state (no pain or baseline pain and ≥1 month from any hospital admission)
• Receiving chronic transfusions (i.e., regular transfusion every 4-8 weeks).

Exclusion Criteria:

• History of transfusion reactions not adequately managed by antihistamines
• Does not have crossmatch compatible red cells
• Known G6PD deficiency
• Hepato- or splenomegaly
• Participation in another therapeutic trial
• Pregnant or nursing
• HIV positive
• At investigator discretion for uncontrolled inter-current illness or social situation limiting compliance with study requirements.
• Inability to speak and/or read English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: G6PD Deficient Red Blood Cell Transfusion, then Non-G6PD deficient Red Blood Cell Transfusion; Transfusion of a red blood cell unit that has been identified by local laboratory procedures to be deficient in G6PD enzyme activity followed after 4 months by transfusion of a red blood cell unit that has been identified by local laboratory procedures to not be deficient in G6PD enzyme activity.	Biological: G6PD Deficient Red Blood Cell Transfusion; Patients will receive a red blood cell transfusion. The last 50 mL of the transfusion will be labeled with chromium to allow investigators to study the lifespan of the red blood cells transfused into each patient.; Biological: Non-G6PD deficient Red Blood Cell Transfusion; Patients will receive a red blood cell transfusion. The last 50 mL of the transfusion will be labeled with chromium to allow investigators to study the lifespan of the red blood cells transfused into each patient.
Active Comparator: Non-G6PD deficient Red Blood Cell Transfusion, then G6PD Deficient Red Blood Cell Transfusion,; Transfusion of a red blood cell unit that has been identified by local laboratory procedures to not be deficient in G6PD enzyme activity followed after 4 months by transfusion of a red blood cell unit that has been identified by local laboratory procedures to be deficient in G6PD enzyme activity	Biological: G6PD Deficient Red Blood Cell Transfusion; Patients will receive a red blood cell transfusion. The last 50 mL of the transfusion will be labeled with chromium to allow investigators to study the lifespan of the red blood cells transfused into each patient.; Biological: Non-G6PD deficient Red Blood Cell Transfusion; Patients will receive a red blood cell transfusion. The last 50 mL of the transfusion will be labeled with chromium to allow investigators to study the lifespan of the red blood cells transfused into each patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Red Blood Cells Surviving	Post-Transfusion Recovery	24 hours post-transfusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Hemoglobin A	Hemoglobin A	1 hour post-transfusion, 4 weeks post-transfusion

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Columbia University
• Investigators: Principal Investigator: Matthew Karafin, MD, MS, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2022
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: July 19, 2019
• First Posted (Actual): July 23, 2019

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: 21-0587; R01HL148151-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: 9 to 36 months following publication
• IPD Sharing Access Criteria: Investigator proposing to use the data has approval from an IRB, IEC, or REB and an executed data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No