Sickle Cell Disease Without Crisis
Conditions
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.
Interventions
BIOLOGICALG6PD 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.
BIOLOGICALNon-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.
Sponsors
Columbia University
National Heart, Lung, and Blood Institute (NHLBI)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Masking description
Patients will not be told which type of blood they are receiving first. There is no way to tell if blood has enzyme deficiencies by looking at it.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Red Blood Cells Surviving | 24 hours post-transfusion | Post-Transfusion Recovery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in Hemoglobin A | 1 hour post-transfusion, 4 weeks post-transfusion | Hemoglobin A |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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.
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. | 3 |
| 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
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.
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. | 5 |
| Total | 8 |
Baseline characteristics
| Characteristic | G6PD Deficient Red Blood Cell Transfusion, Then Non-G6PD Deficient Red Blood Cell Transfusion | Non-G6PD Deficient Red Blood Cell Transfusion, Then G6PD Deficient Red Blood Cell Transfusion, | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 2 / 3 | 1 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 5 |
Outcome results
Primary
Percentage of Red Blood Cells Surviving
Post-Transfusion Recovery
Time frame: 24 hours post-transfusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| G6PD Deficient Red Blood Cell Transfusion | Percentage of Red Blood Cells Surviving | 82.91 percentage of surviving red cells | Standard Deviation 5.57 |
| Non-G6PD Deficient Red Blood Cell Transfusion | Percentage of Red Blood Cells Surviving | 91.03 percentage of surviving red cells | Standard Deviation 3.9 |
Secondary
Mean Percent Change in Hemoglobin A
Hemoglobin A
Time frame: 1 hour post-transfusion, 4 weeks post-transfusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| G6PD Deficient Red Blood Cell Transfusion | Mean Percent Change in Hemoglobin A | 25.87 Percentage of Hemoglobin A | Standard Deviation 8.14 |
| Non-G6PD Deficient Red Blood Cell Transfusion | Mean Percent Change in Hemoglobin A | 21.02 Percentage of Hemoglobin A | Standard Deviation 3.55 |