Healthy
Conditions
Brief summary
This is a single-center, randomized, partially blinded study to determine whether 42-day old red blood cells (RBCs) deliver oxygen as effectively as 7-day old RBCs and also to determine whether transfusion with 28-day old RBCs is non-inferior to 7-day old RBCs with respect to oxygen delivery. In this study, subjects will be randomized to be transfused with 2 units of autologous (one's own) RBCs that are either 7-, 28-, or 42-days old. Endpoints include changes in exercise duration and VO2 max (test of oxygen consumption/delivery) between groups.
Detailed description
The US Food and Drug Administration (FDA) regulations permit additive-containing RBCs to be stored for up to 42 days prior to transfusion. However, RBCs progressively develop abnormalities during storage. The efficacy of older stored blood, i.e., effective oxygen delivery, has not been established in rigorous controlled studies. Due to pragmatic reasons, a large clinical trial that randomizes patients to old blood may not be feasible. Every subject will have 2 phlebotomy visits at Stony Brook University Hospital. Subjects randomized to the 7- and 42-day old groups will have 2 units of blood removed at Week 0 and another 2 units removed at Week 5. However, the remaining 28-day group will have 2 units of blood removed at Week 2 and only 1 unit of blood removed at Week 5. During week 6, each subjects will have 3 study visits: 1) On Monday, a VO2 max test; 2) On Wednesday, a transfusion with 2 units of autologous RBCs (each over 1 hour), followed by a VO2 max test 2 hours later; 3) On Friday, a VO2 max test will be done in order to calculate a delta VO2 max (Friday minus Monday results).
Interventions
BIOLOGICALTransfusion of 7-day stored red blood cells
Subjects will donate blood at Week 0 and Week 5 of their participation and receive, at Week 6, back a transfusion of their Week 5 (7-day old) red blood cells.
BIOLOGICALTransfusion of 28-day stored red blood cells
Subjects will donate blood at Week 2 and Week 5 of their participation and receive, at Week 6, back a transfusion of their Week 2 (28-day old) red blood cells.
BIOLOGICALTransfusion of 42-day stored red blood cells
Subjects will donate blood at Week 0 and Week 5 of their participation and receive, at Week 6, back a transfusion of their Week0 (42-day old) red blood cells.
Sponsors
Stony Brook University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Habitual exerciser defined as ≥ 30 minutes of at least moderate or high intensity exercise ≥ 3 times per week. After consent, and at the subsequent screening visit, a VO2 max test will be performed, and subjects with a low value (\< 35 mL/kg/min) will be excluded (screen failure). Based on our previous experience, we anticipate that \<10% of the subjects will fall into this category * Calculated total blood volume (TBV) ≥4,500 mL using an established formula: 1. Men: (0.006012 x H3) + (14.6 x W) + 604 = TBV 2. Women: (0.005835 x H3) + (15 x W) + 183 = TBV \[H=height in inches; W=weight in pounds\] * Has access to transportation to visit the blood collection facility and to return to Stony Brook for all study visits.
Exclusion criteria
* Any significant acute or chronic medical illness or problem, including, but not limited to, diabetes, hypertension, cardiac disease, asthma, chronic obstructive lung disease * Current or recent (last 60 days) tobacco or nicotine use * History of sickle cell trait or disease or any other acquired or hereditary hematological abnormality * History of fainting or other significant adverse reaction during phlebotomy or donation of blood * Known prolonged corrected QT interval (or evidence of such at screening) on electrocardiogram defined as \>470 ms * Known or suspected illicit drug or alcohol abuse * Known or suspected HIV, Hepatitis B, or Hepatitis C infection * History of thrombophilia or anticoagulant therapy * Pregnancy * Obesity defined as BMI\>30 * Recent history of blood donation: a) Single whole blood unit donation within the past 8 weeks; b) Double RBC donation by apheresis within the past 16 weeks; or c) Plasma donation by apheresis within the past 4 weeks * Inadequate RBC mass based on TBV \<4500 ml (above) or screening Hb \<14 g/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Maximal Oxygen Uptake (VO2 Max) After Blood Cell Transfusion | Baseline (prior to receiving blood) and Day 2 after receiving blood | Percent Change From Baseline in Maximal Oxygen Uptake (VO2 Max) on Day 2 After Blood Cell Transfusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Duration of Exercise From Baseline to Day 2 After RBC Transfusion | Baseline and Day 2 after transfusion | Percent change in duration of exercise from baseline to day 2 after red blood cell transfusion |
Countries
United States
Participant flow
Recruitment details
42 randomized
Participants by arm
| Arm | Count |
|---|---|
| 7-day Old RBCs Transfusion of 7-day stored red blood cells: Subjects will be transfused with their own 7-day old red blood cells
Transfusion of 7-day stored red blood cells: Subjects will donate blood at Week 0 and Week 5 of their participation and receive, at Week 6, back a transfusion of their Week 5 (7-day old) red blood cells. | 10 |
| 28-day Old RBCs Transfusion of 28-day stored red blood cells: Subjects will be transfused with their own 28-day old red blood cells
Transfusion of 28-day stored red blood cells: Subjects will donate blood at Week 2 and Week 5 of their participation and receive, at Week 6, back a transfusion of their Week 2 (28-day old) red blood cells. | 10 |
| 42-day Old RBCs Transfusion of 42-day stored red blood cells: Subjects will be transfused with their own 42-day old red blood cells
Transfusion of 42-day stored red blood cells: Subjects will donate blood at Week 0 and Week 5 of their participation and receive, at Week 6, back a transfusion of their Week0 (42-day old) red blood cells. | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | 7-day Old RBCs | 28-day Old RBCs | 42-day Old RBCs | Total |
|---|---|---|---|---|
| Age, Continuous | 22.5 years | 23.5 years | 23 years | 23 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 8 Participants | 10 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Percent Change From Baseline in Maximal Oxygen Uptake (VO2 Max) After Blood Cell Transfusion
Percent Change From Baseline in Maximal Oxygen Uptake (VO2 Max) on Day 2 After Blood Cell Transfusion
Time frame: Baseline (prior to receiving blood) and Day 2 after receiving blood
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 7-day Old RBCs | Percent Change From Baseline in Maximal Oxygen Uptake (VO2 Max) After Blood Cell Transfusion | 10.5 percent change |
| 28-day Old RBCs | Percent Change From Baseline in Maximal Oxygen Uptake (VO2 Max) After Blood Cell Transfusion | 8.5 percent change |
| 42-day Old RBCs | Percent Change From Baseline in Maximal Oxygen Uptake (VO2 Max) After Blood Cell Transfusion | 10.9 percent change |
Secondary
Percent Change in Duration of Exercise From Baseline to Day 2 After RBC Transfusion
Percent change in duration of exercise from baseline to day 2 after red blood cell transfusion
Time frame: Baseline and Day 2 after transfusion
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 7-day Old RBCs | Percent Change in Duration of Exercise From Baseline to Day 2 After RBC Transfusion | 5.4 percent change |
| 28-day Old RBCs | Percent Change in Duration of Exercise From Baseline to Day 2 After RBC Transfusion | 5.4 percent change |
| 42-day Old RBCs | Percent Change in Duration of Exercise From Baseline to Day 2 After RBC Transfusion | 4.9 percent change |