Clinical trial NCT02889133: Donor Iron Deficiency Study - Red Blood Cells From Iron-deficient Donors: Recovery and Storage Quality
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Iron Deficiency
Keywords: Iron deficiency
Transfusion
Blood donation
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: New York Blood Center
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2016-09-05
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 18-75 years old;
2. healthy (by self report);
3. body weight \>110 lbs;
4. female hematocrit \>=38%, male hematocrit \>39%;
5. frequent blood donor (men ≥2 and female ≥1 RBC unit donations in past year);
6. ferritin \<=15 ng/mL; and
7. zinc protoporphyrin \>=60 µmol/mol heme.

Exclusion Criteria:

1. ineligible for donation based on the New York Blood Center donor autologous questionnaire;
2. taking iron supplementation;
3. C-reactive protein \>10 mg/L;
4. sickle cell trait;
5. systolic blood pressure \>180 or \<90 mm Hg, diastolic blood pressure \>100 or \<50 mm Hg;
6. heart rate \<50 or \>100;
7. temperature \>99.5°F prior to donation;
8. 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);
9. positive results on standard blood donor infectious disease testing;
10. pregnancy;
11. taking, or planning to take, iron supplements; and
12. history of severe asthma requiring hospitalization, allergic eczema (atopic dermatitis), or other atopic allergy causing anaphylaxis.

Primary outcomes:
measure: 51-Chromium 24-hour Post-transfusion RBC Recovery of Units
timeFrame: Performed 42 days after blood donation
Secondary outcomes:
measure: RBC Zinc Protoporphyrin Levels
timeFrame: End of participation (e.g., ~6 months)
measure: Serum Ferritin
timeFrame: End of participation (e.g., ~6 months)
measure: Hemoglobin
timeFrame: End of participation (e.g., ~6 months)
measure: Reticulocyte Hemoglobin
timeFrame: End of participation (e.g., ~6 months)
measure: Soluble Transferrin Receptor
timeFrame: End of participation (e.g., ~6 months)
measure: Hepcidin
timeFrame: End of participation (e.g., ~6 months)
measure: Transferrin Saturation
timeFrame: End of participation (e.g., ~6 months)
measure: SF-36 Physical Functioning Score
timeFrame: End of participation (e.g., ~6 months)
measure: SF-36 Role Functioning/Physical Score
timeFrame: End of participation (e.g., ~6 months)
measure: SF-36 Role Functioning/Emotional Score
timeFrame: End of participation (e.g., ~6 months)
measure: SF-36 Energy/Fatigue Score
timeFrame: End of participation (e.g., ~6 months)
measure: SF-36 Emotional Well-being Score
timeFrame: End of participation (e.g., ~6 months)
measure: SF-36 Social Functioning Score
timeFrame: End of participation (e.g., ~6 months)
measure: SF-36 Pain Score
timeFrame: End of participation (e.g., ~6 months)
measure: SF-36 General Health Score
timeFrame: End of participation (e.g., ~6 months)
measure: SF-36 Health Change Score
timeFrame: End of participation (e.g., ~6 months)
measure: Beck Depression Inventory (BDI) II Score
timeFrame: End of participation (e.g., ~6 months)
measure: Beck Anxiety Inventory (BAI) Score
timeFrame: End of participation (e.g., ~6 months)
measure: Global Fatigue Index (GFI) Score
timeFrame: End of participation (e.g., ~6 months)
measure: Restless Legs Syndrome Rating Scale Score
timeFrame: End of participation (e.g., ~6 months)
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Eldad A. Hod, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moroff G, Sohmer PR, Button LN. Proposed standardization of methods for determining the 24-hour survival of stored red cells. Transfusion. 1984 Mar-Apr;24(2):109-14. doi: 10.1046/j.1537-2995.1984.24284173339.x.
citation: Hod EA, Brittenham GM, Bitan ZC, Feit Y, Gaelen JI, La Carpia F, Sandoval LA, Zhou AT, Soffing M, Mintz A, Schwartz J, Eng C, Scotto M, Caccappolo E, Habeck C, Stern Y, McMahon DJ, Kessler DA, Shaz BH, Francis RO, Spitalnik SL. A randomized trial of blood donor iron repletion on red cell quality for transfusion and donor cognition and well-being. Blood. 2022 Dec 22;140(25):2730-2739. doi: 10.1182/blood.2022017288.
citation: Roussel C, Morel A, Dussiot M, Marin M, Colard M, Fricot-Monsinjon A, Martinez A, Chambrion C, Henry B, Casimir M, Volle G, Depond M, Dokmak S, Paye F, Sauvanet A, Le Van Kim C, Colin Y, Georgeault S, Roingeard P, Spitalnik SL, Ndour PA, Hermine O, Hod EA, Buffet PA, Amireault P. Rapid clearance of storage-induced microerythrocytes alters transfusion recovery. Blood. 2021 Apr 29;137(17):2285-2298. doi: 10.1182/blood.2020008563.