Donor Iron Deficiency Study - Red Blood Cells From Iron-deficient Donors: Recovery and Storage Quality

Study Overview
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Brief Summary
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Primary Hypothesis The 24-hour post-transfusion RBC recovery of units obtained from donors exhibiting iron-deficient erythropoiesis will not meet FDA standards for clinical use. The 24-hour post-transfusion RBC recovery of units obtained after intravenous iron repletion will improve significantly and will meet FDA standards for clinical use.

Detailed Description
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Iron deficiency is common among regular blood donors, but the recovery and quality of red blood cell (RBC) units from iron-deficient donors has not been rigorously examined. Evidence from both animal and human studies indicate that when the iron supply for erythropoiesis is inadequate, the RBCs produced have multiple metabolic defects that impair their ability to tolerate refrigerated storage. Studies in a mouse model demonstrated decreased post-transfusion recovery of refrigerator-stored RBCs obtained from iron-deficient donors. The planned studies will identify human donors at greatest risk of providing RBCs with poor post-transfusion recovery by using a combination of a decreased serum ferritin concentration and increased RBC zinc protoporphyrin, as described below. To evaluate unequivocally the role of iron deficiency in poor posttransfusion RBC recovery, intravenous iron will be used for iron repletion.

Official Title
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A Randomized Trial to Determine if RBCs From Donors With Iron Deficient Erythropoiesis Have Decreased Post-transfusion RBC Recovery and Whether Iron Repletion Improves Recovery

Conditions
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Iron Deficiency

Intervention / Treatment
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* Drug: Iron-dextran
* Drug: Saline
* Procedure: Blood Donation
* Procedure: 24-hour PTR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years old; healthy (by self report); body weight >110 lbs; female hematocrit >=38%, male hematocrit >39%; frequent blood donor (men ≥2 and female ≥1 RBC unit donations in past year); ferritin <=15 ng/mL; and zinc protoporphyrin >=60 µmol/mol heme. Exclusion Criteria: ineligible for donation based on the New York Blood Center donor autologous questionnaire; taking iron supplementation; C-reactive protein >10 mg/L; sickle cell trait; systolic blood pressure >180 or <90 mm Hg, diastolic blood pressure >100 or <50 mm Hg; heart rate <50 or >100; temperature >99.5°F prior to donation; temperature >100.4°F or subjective feeling of illness prior to 51-Chromium 24-hour RBC recovery study (to avoid the subject having a concurrent illness that may affect post-transfusion recovery); positive results on standard blood donor infectious disease testing; pregnancy; taking, or planning to take, iron supplements; and history of severe asthma requiring hospitalization, allergic eczema (atopic dermatitis), or other atopic allergy causing anaphylaxis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Iron repletion<br>Subjects will donate blood donation and undergo 24-hour PTR and receive IV iron-dextran. After 5 months, subjects will donate blood again, receive IV saline and undergo 24-hour PTR. | Drug: Iron-dextran<br>* Approved for clinical use: 1-gram dose IV - diluted in 500 mL, one pint normal saline.<br>* Other names: Low molecular weight iron-dextran;Drug: Saline<br>* Salt water IV - 500 mL, one pint normal saline.<br>* Other names: Normal Saline;Procedure: Blood Donation<br>* Standard process of collecting and storing blood and blood components (approximately 450 mL, or a pint of blood). Following donation, the blood will be leukoreduced, packed, and stored in AS-3 solution.<br>* Other names: Red blood cell donation;Procedure: 24-hour PTR<br>* The way the FDA determines how good blood is for transfusion is called a radioactive 51-Chromium 24-hour post-transfusion red cell recovery study. The purpose is to measure how many of the transfused red cells are still in circulation (being pumped by the heart through blood vessels) 24 hours after transfusion. In order to measure the percent of red cells that are still in circulation, a small amount of the donated blood will be radioactively labeled. This will be infused in one arm and then blood will be collected from the other arm at different time points to measure how much of the transfused red cells are still in circulation.<br>* Other names: 24-hour post-transfusion red cell recovery;|
| Placebo Comparator: Placebo<br>Subjects will donate blood donation and undergo 24-hour PTR and receive IV saline. After 5 months, subjects will donate blood again, receive IV iron-dextran and undergo 24-hour PTR. | Drug: Iron-dextran<br>* Approved for clinical use: 1-gram dose IV - diluted in 500 mL, one pint normal saline.<br>* Other names: Low molecular weight iron-dextran;Drug: Saline<br>* Salt water IV - 500 mL, one pint normal saline.<br>* Other names: Normal Saline;Procedure: Blood Donation<br>* Standard process of collecting and storing blood and blood components (approximately 450 mL, or a pint of blood). Following donation, the blood will be leukoreduced, packed, and stored in AS-3 solution.<br>* Other names: Red blood cell donation;Procedure: 24-hour PTR<br>* The way the FDA determines how good blood is for transfusion is called a radioactive 51-Chromium 24-hour post-transfusion red cell recovery study. The purpose is to measure how many of the transfused red cells are still in circulation (being pumped by the heart through blood vessels) 24 hours after transfusion. In order to measure the percent of red cells that are still in circulation, a small amount of the donated blood will be radioactively labeled. This will be infused in one arm and then blood will be collected from the other arm at different time points to measure how much of the transfused red cells are still in circulation.<br>* Other names: 24-hour post-transfusion red cell recovery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 51-Chromium 24-hour post-transfusion RBC recovery of units |  | Performed 42 days after blood donation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RBC zinc protoporphyrin levels | Measured in a clinical laboratory. Will be used to determine the association between pre-donation zinc protoporphyrin levels and post-transfusion recovery along with the effect of treatment on zinc protoporphyrin levels. | Day 0-end of participation (e.g.,  6 months) | 
| Serum ferritin | Measured in a clinical laboratory. Will be used to determine the association between pre-donation ferritin levels and post-transfusion recovery along with the effect of treatment on ferritin levels. | Day 0-end of participation (e.g.,  6 months) | 
| Hemoglobin | Measured in a clinical laboratory. Will be used to determine the association between pre-donation hemoglobin levels and post-transfusion recovery along with the effect of treatment on hemoglobin levels. | Day 0-end of participation (e.g.,  6 months) | 
| Reticulocyte Hemoglobin | Measured in a clinical laboratory. Will be used to determine the association between pre-donation reticulocyte hemoglobin levels and post-transfusion recovery along with the effect of treatment on reticulocyte hemoglobin levels. | Day 0-end of participation (e.g.,  6 months) | 
| Soluble transferrin receptor | Measured in a clinical laboratory. Will be used to determine the association between pre-donation soluble transferrin receptor levels and post-transfusion recovery along with the effect of treatment on soluble transferrin receptor levels. | Day 0-end of participation (e.g.,  6 months) | 
| Hepcidin | Measured as a research use only test in a research laboratory using an ELISA from Intrinsic LifeSciences. Will be used to determine the association between pre-donation hepcidin levels and post-transfusion recovery along with the effect of treatment on hepcidin levels. | Day 0-end of participation (e.g.,  6 months) | 
| Transferrin saturation | Measured in a clinical laboratory. Will be used to determine the association between pre-donation transferrin saturation levels and post-transfusion recovery along with the effect of treatment on transferrin saturation levels. | Day 0-end of participation (e.g.,  6 months) | 
| SF-36 Physical functioning score | Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health. | Day 0-end of participation (e.g.,  6 months) | 
| SF-36 Role functioning/physical score | Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health. | Day 0-end of participation (e.g.,  6 months) | 
| SF-36 Role functioning/emotional score | Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health. | Day 0-end of participation (e.g.,  6 months) | 
| SF-36 Energy/fatigue score | Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health. | Day 0-end of participation (e.g.,  6 months) | 
| SF-36 Emotional well-being score | Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health. | Day 0-end of participation (e.g.,  6 months) | 
| SF-36 Social functioning score | Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health. | Day 0-end of participation (e.g.,  6 months) | 
| SF-36 Pain score | Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health. | Day 0-end of participation (e.g.,  6 months) | 
| SF-36 General health score | Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health. | Day 0-end of participation (e.g.,  6 months) | 
| SF-36 Health change score | Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health. | Day 0-end of participation (e.g.,  6 months) | 
| Beck Depression Inventory (BDI) II score | Evaluating subjects' depression using the Beck Depression Inventory-II survey. Scores range from 0-63 with higher scores indicating more severe depression. | Day 0-end of participation (e.g.,  6 months) | 
| Beck Anxiety Inventory (BAI) score | Evaluating subjects' anxiety using the Beck Anxiety Inventory survey. Scores range from 0-63 with higher scores indicating more severe anxiety. | Day 0-end of participation (e.g.,  6 months) | 
| Global Fatigue Index (GFI) score | Evaluating subjects' fatigue using the Multidimensional Assessment of Fatigue (MAF) survey. Scores range from 1-50 with higher scores indicating more severe fatigue. | Day 0-end of participation (e.g.,  6 months) | 
| Restless Legs Syndrome Rating Scale score | Evaluating subjects' symptoms of restless leg syndrome using the Restless Legs Syndrome Rating Scale survey. Scores range from 0-40 with higher scores indicating more severe symptoms. | Day 0-end of participation (e.g.,  6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron deficiency, Transfusion, Blood donation