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

Not Applicable

Completed

• Conditions: Iron Deficiency
• Interventions: Drug: Iron-dextran; Drug: Saline; Procedure: Blood Donation; Procedure: 24-hour PTR

• Registration Number: NCT02889133
• Lead Sponsor: Columbia University

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.

Study Timeline

• Study First Submitted: 2016-08-25
• Study First Submitted QC: 2016-08-30
• Study First Posted: 2016-09-05
• Study Start: 2017-01
• Primary Completion: 2021-10-05
• Study Completion: 2021-10-05
• Results First Submitted: 2023-12-14
• Status Verified: 2024-06
• Results First Submitted QC: 2024-06-10
• Last Update Submitted: 2024-06-10
• Results First Posted: 2024-06-12
• Last Update Posted: 2024-06-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Saline	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.
Iron repletion	Blood Donation	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.
Placebo	Blood Donation	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.
Placebo	24-hour PTR	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.
Iron repletion	24-hour PTR	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.
Placebo	Iron-dextran	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.
Iron repletion	Iron-dextran	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.
Iron repletion	Saline	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.

Primary Outcome Measures

Name	Time	Method
51-Chromium 24-hour Post-transfusion RBC Recovery of Units	Performed 42 days after blood donation	Comparison of the percentage change in 51-Chromium-labeled RBCs remaining from pre- and 24 hour post-transfusion measurement between the Iron Repletion and the Placebo group. The post-transfusion recovery represents the percent of 51-Chromium-labeled RBCs remaining in circulation 24 hours after infusion as compared to an extrapolated time zero measurement.

Secondary Outcome Measures

Name	Time	Method
Reticulocyte Hemoglobin	End of participation (e.g., ~6 months)	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.
Hemoglobin	End of participation (e.g., ~6 months)	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.
RBC Zinc Protoporphyrin Levels	End of participation (e.g., ~6 months)	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.
Serum Ferritin	End of participation (e.g., ~6 months)	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.
Soluble Transferrin Receptor	End of participation (e.g., ~6 months)	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.
Hepcidin	End of participation (e.g., ~6 months)	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.
Transferrin Saturation	End of participation (e.g., ~6 months)	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.
SF-36 Physical Functioning Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Role Functioning/Physical Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Role Functioning/Emotional Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Energy/Fatigue Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Emotional Well-being Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Social Functioning Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Pain Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 General Health Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Health Change Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
Beck Depression Inventory (BDI) II Score	End of participation (e.g., ~6 months)	Evaluating subjects' depression using the Beck Depression Inventory-II survey. Scores range from 0-63 with higher scores indicating more severe depression.
Restless Legs Syndrome Rating Scale Score	End of participation (e.g., ~6 months)	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.
Beck Anxiety Inventory (BAI) Score	End of participation (e.g., ~6 months)	Evaluating subjects' anxiety using the Beck Anxiety Inventory survey. Scores range from 0-63 with higher scores indicating more severe anxiety.
Global Fatigue Index (GFI) Score	End of participation (e.g., ~6 months)	Evaluating subjects' fatigue using the Multidimensional Assessment of Fatigue (MAF) survey. Scores range from 1-50 with higher scores indicating more severe fatigue.

Trial Locations

Locations (1)

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States