VO2 Max: In Vivo Model for Functional Red Cell Testing. Can RECESS be Explained?

Study Overview
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Brief Summary
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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
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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).

Official Title
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VO2 Max: In Vivo Model for Functional Red Cell Testing. Can RECESS be Explained?

Conditions
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Healthy

Intervention / Treatment
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* Biological: Transfusion of 7-day stored red blood cells
* Biological: Transfusion of 28-day stored red blood cells
* Biological: Transfusion of 42-day stored red blood cells


Participation Criteria
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Eligibility Criteria
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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: Men: (0.006012 x H3) + (14.6 x W) + 604 = TBV 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 7-day old RBCs<br>Transfusion of 7-day stored red blood cells: Subjects will be transfused with their own 7-day old red blood cells | Biological: Transfusion of 7-day stored red blood cells<br>* 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.<br>|
| Experimental: 28-day old RBCs<br>Transfusion of 28-day stored red blood cells: Subjects will be transfused with their own 28-day old red blood cells | Biological: Transfusion of 28-day stored red blood cells<br>* 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.<br>|
| Experimental: 42-day old RBCs<br>Transfusion of 42-day stored red blood cells: Subjects will be transfused with their own 42-day old red blood cells | Biological: Transfusion of 42-day stored red blood cells<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Baseline (prior to receiving blood) and Day 2 after receiving blood | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Baseline and Day 2 after transfusion |