Transfusion of Biotin-Labeled Red Blood Cells

Transfusion of Biotin-Labeled Red Blood Cells for the Evaluation of Genetic Factors That Contribute to Donor Differences in Red Blood Cell Storage and Post-Transfusion Red Blood Cell Recovery

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.

Study Overview

• Status: Terminated
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: Biotin-Labeled Red Blood Cells

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Biotin-Labeled Red Blood Cells Infusion; Each participant will receive 2 transfusions of biotin labeled red blood cells.	Biological: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 hours, 30 days and 60 days after transfusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5-7 days and 35-42 days following blood donation
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.	5-7 days and 35-42 days following blood donation
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.	5-7 days and 35-42 days following blood donation

Collaborators and Investigators

• Sponsor: Gladwin, Mark, MD
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 16, 2019
• Primary Completion (ACTUAL): March 2, 2021
• Study Completion (ACTUAL): June 29, 2021

Study Registration Dates

• First Submitted: November 22, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (ACTUAL): December 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 21, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Biotin labeled red blood cells; BioRBCs
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Biotin
• Other Study ID Numbers: STUDY19020356; 5R01HL098032-09 (NIH)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No