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

Iron Deficiency Clinical Trial

— DIDS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02889133
• Other study ID #: AAAQ8875
• Secondary ID: 1R01HL133049-01
• Status: Completed
• Phase: N/A
• Start date: January 2017
• Est. completion date: October 5, 2021

Study information

• Verified date: June 2024
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: October 5, 2021
• Est. primary completion date: October 5, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Iron Deficiency

Intervention

Drug:
• Iron-dextran
Approved for clinical use: 1-gram dose IV - diluted in 500 mL, one pint normal saline.
• Saline
Salt water IV - 500 mL, one pint normal saline.

Procedure:
• Blood Donation
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.
• 24-hour PTR
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.

Locations

Country	Name	City	State
United States	Columbia University Irving Medical Center	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Columbia University	National Heart, Lung, and Blood Institute (NHLBI), New York Blood Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	51-Chromium 24-hour Post-transfusion RBC Recovery of Units	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.	Performed 42 days after blood donation
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)
Secondary	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.	End of participation (e.g., ~6 months)