Healthy Volunteers
Conditions
Keywords
BioRBCs, Biotin labeled red blood cells
Brief summary
The purpose of this research is to evaluate the impact of genetic and biologic factors in blood donors on red blood cell storage stability after autologous transfusion over the different range of storage period of 5-7 days and 35-42 days in healthy volunteers.
Interventions
BIOLOGICALBiotin-Labeled Red Blood Cells
We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage).
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Gladwin, Mark, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Ages 18 years and older * Weight ≥110 lbs * Hemoglobin ≥ 12.5 g/dL or hematocrit ≥ 38% for women and hemoglobin ≥ 13.0 g/dL or hematocrit ≥ 39% for men. * Meet criteria for autologous blood donation
Exclusion criteria
* Subjects with a past medical history or symptoms of blood dyscrasia, diabetes mellitus, hyperlipidemia, obstructive sleep apnea, renal disease, congestive heart failure, significant cardiac disease and / or known peripheral arterial disease. * Moderate to severe systemic hypertension (systolic blood pressure \>140 mmHg and/or diastolic blood pressure \> 95 mmHg * Systolic blood pressure \<100 mmHg and/or diastolic blood pressure \< 60 mmHg on the study day. * Positive Direct Antiglobulin Test * Consumption of biotin supplements or raw eggs within 30 days * Treatment with antibiotics in the week before initiating study participation to avoid suppression of erythropoiesis, which may accompany infection. * Blood loss in the previous 8 weeks due to epistaxis, trauma, hemoptysis, gastrointestinal bleeding, diagnostic phlebotomy (\> 30 ml) * Subjects who report tobacco or marijuana smoking within 6 months of study. * Cognitively impaired subjects, or institutionalized persons and subjects unable or unwilling to complete written informed consent * Subjects with a history of blood donation within the last 56 days. * Use of other investigational drugs/devices within 30 days of screening. * Subjects taking any medication for the treatment of diabetes including insulin * Females of childbearing potential who are pregnant or unwilling to undergo pregnancy testing; females with positive pregnancy testing on screening day will be excluded. * History of prior transfusion reaction to blood products. * Allergic reaction to biotin * Donors with naturally occurring antibodies against BioRBCs will be excluded from the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Biotin Labeled Red Blood Cells | 24 hours, 30 days and 60 days after transfusion | This will be determined using enumeration of biotinylated red blood cells obtained by flow cytometry from blood samples obtained at various time points from subjects with specified genetic mutations, compared with control subjects without the specified mutation. Percentage of Biotin Labeled Red Blood Cells is determined by Biotin Labeled Red Blood Cells in circulation at each time point/baseline Biotin Labeled Red Blood Cells in circulation x 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Storage Hemolysis | 5-7 days and 35-42 days following blood donation | This will be quantified as percent hemolysis, which accounts for the levels of RBC-derived free hemoglobin in response to cold storage. We will define the associations between the primary endpoints and the quantification of storage hemolysis. Quantification of storage hemolysis is based on this equation: (sample hematocrit x levels of free hemoglobin obtained after centrifugation measured in the supernatant / the total amount of sample hemoglobin before centrifugation) x 100. |
| The Percentage of Red Blood Cell Osmotic Hemolysis | 5-7 days and 35-42 days following blood donation | This will be quantified by the evaluation of osmotic stress assays. We will define the associations between the primary endpoints and the quantification of osmotic hemolysis. The percent osmotic hemolysis is determined by this equation: (supernatant cell-free hemoglobin of pink test-treated RBCs / total amount of hemoglobin) x 100. |
| The Percentage of Red Blood Cell Oxidative Hemolysis | 5-7 days and 35-42 days following blood donation | This will be quantified by the evaluation of oxidative stress assays. We will define the associations between the primary endpoints and the quantification of oxidative hemolysis. The percent osmotic hemolysis is determined by this equation: (supernatant cell-free hemoglobin of 2,2'-azobis-2-methyl-propanimidamide, dihydrochloride treated RBCs - supernatant cell-free hemoglobin of untreated red blood cells / total amount of hemoglobin) x 100. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Biotin-Labeled Red Blood Cells Infusion Each participant will receive 2 transfusions of biotin labeled red blood cells.
Biotin-Labeled Red Blood Cells: We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage). | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
Baseline characteristics
| Characteristic | Biotin-Labeled Red Blood Cells Infusion |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Percentage of Biotin Labeled Red Blood Cells
This will be determined using enumeration of biotinylated red blood cells obtained by flow cytometry from blood samples obtained at various time points from subjects with specified genetic mutations, compared with control subjects without the specified mutation. Percentage of Biotin Labeled Red Blood Cells is determined by Biotin Labeled Red Blood Cells in circulation at each time point/baseline Biotin Labeled Red Blood Cells in circulation x 100.
Time frame: 24 hours, 30 days and 60 days after transfusion
Population: The blood sample at 24 hours from one of the 4 completed subjects was not collected.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Biotin-Labeled Red Blood Cells Infusion | Percentage of Biotin Labeled Red Blood Cells | Percentage of Fresh Biotin Labeled Red Blood Cells at 24 Hours | 99.2 percentage of biotin labeled RBC |
| Biotin-Labeled Red Blood Cells Infusion | Percentage of Biotin Labeled Red Blood Cells | Percentage of Fresh Biotin Labeled Red Blood Cells at Day 30 | 77.2 percentage of biotin labeled RBC |
| Biotin-Labeled Red Blood Cells Infusion | Percentage of Biotin Labeled Red Blood Cells | Percentage of Fresh Biotin Labeled Red Blood Cells at Day 60 | 54.3 percentage of biotin labeled RBC |
| Biotin-Labeled Red Blood Cells Infusion | Percentage of Biotin Labeled Red Blood Cells | Percentage of Aged Biotin Labeled Red Blood Cells at 24 Hours | 99.2 percentage of biotin labeled RBC |
| Biotin-Labeled Red Blood Cells Infusion | Percentage of Biotin Labeled Red Blood Cells | Percentage of Aged Biotin Labeled Red Blood Cells at Day 30 | 75.9 percentage of biotin labeled RBC |
| Biotin-Labeled Red Blood Cells Infusion | Percentage of Biotin Labeled Red Blood Cells | Percentage of Aged Biotin Labeled Red Blood Cells at Day 60 | 51.9 percentage of biotin labeled RBC |
Secondary
The Percentage of Red Blood Cell Osmotic Hemolysis
This will be quantified by the evaluation of osmotic stress assays. We will define the associations between the primary endpoints and the quantification of osmotic hemolysis. The percent osmotic hemolysis is determined by this equation: (supernatant cell-free hemoglobin of pink test-treated RBCs / total amount of hemoglobin) x 100.
Time frame: 5-7 days and 35-42 days following blood donation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biotin-Labeled Red Blood Cells Infusion | The Percentage of Red Blood Cell Osmotic Hemolysis | 5-7 days | 7.4 percentage of osmotic hemolysis | Standard Deviation 4.66 |
| Biotin-Labeled Red Blood Cells Infusion | The Percentage of Red Blood Cell Osmotic Hemolysis | 35-42 days | 7.9 percentage of osmotic hemolysis | Standard Deviation 6.86 |
Secondary
The Percentage of Red Blood Cell Oxidative Hemolysis
This will be quantified by the evaluation of oxidative stress assays. We will define the associations between the primary endpoints and the quantification of oxidative hemolysis. The percent osmotic hemolysis is determined by this equation: (supernatant cell-free hemoglobin of 2,2'-azobis-2-methyl-propanimidamide, dihydrochloride treated RBCs - supernatant cell-free hemoglobin of untreated red blood cells / total amount of hemoglobin) x 100.
Time frame: 5-7 days and 35-42 days following blood donation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biotin-Labeled Red Blood Cells Infusion | The Percentage of Red Blood Cell Oxidative Hemolysis | 5-7 days | 39.93 percentage of oxidative hemolysis | Standard Deviation 12.45 |
| Biotin-Labeled Red Blood Cells Infusion | The Percentage of Red Blood Cell Oxidative Hemolysis | 35-42 days | 46.90 percentage of oxidative hemolysis | Standard Deviation 21.92 |
Secondary
The Percentage of Storage Hemolysis
This will be quantified as percent hemolysis, which accounts for the levels of RBC-derived free hemoglobin in response to cold storage. We will define the associations between the primary endpoints and the quantification of storage hemolysis. Quantification of storage hemolysis is based on this equation: (sample hematocrit x levels of free hemoglobin obtained after centrifugation measured in the supernatant / the total amount of sample hemoglobin before centrifugation) x 100.
Time frame: 5-7 days and 35-42 days following blood donation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biotin-Labeled Red Blood Cells Infusion | The Percentage of Storage Hemolysis | 5-7 days | 0.27 percentage of storage hemolysis | Standard Deviation 0.09 |
| Biotin-Labeled Red Blood Cells Infusion | The Percentage of Storage Hemolysis | 35-42 days | 0.21 percentage of storage hemolysis | Standard Deviation 0.14 |
Post Hoc
Length of Time Biotin-labeled Red Blood Cells Can be Detected Following Infusion
This will be determined using enumeration of biotinylated red blood cells obtained by flow cytometry from blood samples obtained at various time points from subjects.
Time frame: up to 165 days
Population: The fresh stored blood sample from one participant was not collected and analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biotin-Labeled Red Blood Cells Infusion | Length of Time Biotin-labeled Red Blood Cells Can be Detected Following Infusion | Fresh Stored Cells | 135 days | Standard Deviation 12 |
| Biotin-Labeled Red Blood Cells Infusion | Length of Time Biotin-labeled Red Blood Cells Can be Detected Following Infusion | Stored Cells | 104 days | Standard Deviation 12 |