The Impact of Oxidative Stress on Erythrocyte Biology

NCT ID: NCT04028700

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-02
• Study Completion Date: 2024-08-16

Brief Summary

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.

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.

Conditions

Sickle Cell Disease Without Crisis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

G6PD Deficient Red Blood Cell Transfusion

Intervention Type: BIOLOGICAL

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.

Non-G6PD deficient Red Blood Cell Transfusion

Intervention Type: BIOLOGICAL

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.

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

Group Type: ACTIVE_COMPARATOR

G6PD Deficient Red Blood Cell Transfusion

Intervention Type: BIOLOGICAL

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.

Non-G6PD deficient Red Blood Cell Transfusion

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Karafin, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01HL148151-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21-0587

Identifier Type: -

Identifier Source: org_study_id