The Impact of Oxidative Stress on Erythrocyte Biology

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Sickle Cell Disease Without Crisis

Intervention / Treatment
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* Biological: G6PD Deficient Red Blood Cell Transfusion
* Biological: Non-G6PD deficient Red Blood Cell Transfusion


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G6PD Deficient Red Blood Cell Transfusion, then Non-G6PD deficient Red Blood Cell Transfusion<br>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<br>* 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.<br>Biological: Non-G6PD deficient Red Blood Cell Transfusion<br>* 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.<br>|
| Active Comparator: Non-G6PD deficient Red Blood Cell Transfusion, then G6PD Deficient Red Blood Cell Transfusion,<br>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<br>* 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.<br>Biological: Non-G6PD deficient Red Blood Cell Transfusion<br>* 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.<br>|

What is the study measuring?
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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 |