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

Sponsor

Columbia University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02889133

Collaborator

New York Blood Center (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

65.9

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Iron Deficiency	Drug: Iron-dextran Drug: Saline Procedure: Blood Donation Procedure: 24-hour PTR	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

85 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

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

Actual Study Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Iron repletion 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 Approved for clinical use: 1-gram dose IV - diluted in 500 mL, one pint normal saline. Other Names: INFeD Low molecular weight iron-dextran Drug: Saline Salt water IV - 500 mL, one pint normal saline. Other Names: Placebo 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. Other Names: Red blood cell donation Procedure: 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. Other Names: 24-hour post-transfusion red cell recovery
Placebo Comparator: Placebo 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 Approved for clinical use: 1-gram dose IV - diluted in 500 mL, one pint normal saline. Other Names: INFeD Low molecular weight iron-dextran Drug: Saline Salt water IV - 500 mL, one pint normal saline. Other Names: Placebo 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. Other Names: Red blood cell donation Procedure: 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. Other Names: 24-hour post-transfusion red cell recovery

Arm

Intervention/Treatment

Active Comparator: Iron repletion

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

Approved for clinical use: 1-gram dose IV - diluted in 500 mL, one pint normal saline.

Other Names:

INFeD

Low molecular weight iron-dextran

Drug: Saline

Salt water IV - 500 mL, one pint normal saline.

Other Names:

Placebo

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.

Other Names:

Red blood cell donation

Procedure: 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.

Other Names:

24-hour post-transfusion red cell recovery

Placebo Comparator: Placebo

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

Approved for clinical use: 1-gram dose IV - diluted in 500 mL, one pint normal saline.

Other Names:

INFeD

Low molecular weight iron-dextran

Drug: Saline

Salt water IV - 500 mL, one pint normal saline.

Other Names:

Placebo

Normal Saline

Procedure: Blood Donation

Other Names:

Red blood cell donation

Procedure: 24-hour PTR

Other Names:

24-hour post-transfusion red cell recovery

Outcome Measures

Primary Outcome Measures

51-Chromium 24-hour post-transfusion RBC recovery of units [Performed 42 days after blood donation]

Secondary Outcome Measures

RBC zinc protoporphyrin levels [Day 0-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 [Day 0-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.
Hemoglobin [Day 0-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.
Reticulocyte Hemoglobin [Day 0-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.
Soluble transferrin receptor [Day 0-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 [Day 0-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 [Day 0-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 [Day 0-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 [Day 0-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 [Day 0-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 [Day 0-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 [Day 0-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 [Day 0-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 [Day 0-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 [Day 0-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 [Day 0-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 [Day 0-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.
Beck Anxiety Inventory (BAI) score [Day 0-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 [Day 0-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.
Restless Legs Syndrome Rating Scale score [Day 0-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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.