Optimization of Biotinylation Protocol for Studies of Red Blood Cell Survival and Function After Transfusion

NCT06788080 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 11735-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to compare two methods of labeling red blood cells with biotin. The main question to answer is whether red blood cells labeled 48 hours before transfusion survive as long as red blood cells labeled 6 hours before transfusion. Secondary questions are to measure the quality of the red blood cells and whether or not the biotin-labeled red blood cells induce antibodies in transfusion recipients. This study participant will have six study visits:

1. 1.Screening visit, collect 35 ml blood, about 3 tablespoons
2. 2.Donate 500 ml blood
3. 3.Receive 20 ml of biotin labeled blood transfusion, collect 40 ml blood, about 3 tablespoons
4. 4.Return 1 day after transfusion for blood draw (25 ml, about 2 tablespoons)
5. 5.Return 30 days after transfusion for blood draw (25 ml, about 2 tablespoons)
6. 6.Return 90 days after transfusion for blood draw (25 ml, about 2 tablespoons)

Conditions

Measuring Red Blood Cell Survival After Transfusion

Keywords

Biotin; Red blood cell; Transfusion

Outcome Measures

Primary Outcomes (1)

• Percent BioRBC recovery

  The percent recovery of BioRBCs (the percentage of infused BioRBCs remaining in circulation) labeled 48 hours vs. 6 hours prior to transfusion will be tested in each participant. Recovery will be compared between BioRBCs labeled at 6 vs. 48 hours.

  24 hours after transfusion

Secondary Outcomes (4)

• Percent BioRBC recovery

  10 min, 30 min, 1 hour, 30 days, and 90 days after transfusion

• Number of participants who form BioRBC antibodies

  Pre-transfusion and 1, 30, and 90 days after transfusion

• Percent of cells with BioRBC oxidative stress

  10 min, 30 min, 1 hour, 1 day, 30 days, and 90 days after transfusion

• Percent of BioRBCs expressing phosphatidyl serine

  10 min, 30 min, 1 hour, 1 day, 30 days, and 90 days after transfusion

Study Arms (1)

BioRBC arm

EXPERIMENTAL

Each subject will receive biotin labeled red blood cells stored for 6 hours and 24 hours (two separate aliquots infused sequentially).

Drug: BioRBC

Interventions

BioRBC DRUG

Autologous biotin-labeled RBCs will be transfused to study participants

BioRBC arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older;
• Self-report that he or she feels well and healthy;
• Be able and willing to provide written informed consent;
• Be available for the duration of the trial (up to 28 weeks) and able to come to the treatment clinic for scheduled trial visits. This includes screening up to a month before blood donation, a blood donation, BioRBC transfusion (37-42 days after blood donation), and follow up visits 24h, 30 and 90 days after transfusion.
• Females should either be surgically sterile (hysterectomy or tubal ligation) or should use a highly effective, medically accepted contraceptive regimen. Highly effective methods of birth control are defined as those that result in a lower failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, condoms with spermicide, or vasectomized partner.
• All females must have a negative pregnancy test prior to enrollment. Post-menopausal females (women over 50 years of age who, in the absence of pregnancy, have a minimum of 2 months without menses) and females who have had a hysterectomy or oophorectomy will not be tested; and
• Understand the English language.

You may not qualify if:

• Other previously diagnosed RBC disorders (sickle cell disease, thalassemia, spherocytosis, hemoglobin variants);
• Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational process administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the individual inappropriate for entry into this study or would prevent completion of the study;
• Participation in another research study with an investigational drug within four weeks prior to or during the planned study duration;
• Positive screen for anti-BioRBC antibodies detectable using ID-MTS Gel Cards (Ortho Clinical Diagnostics);
• Known liver, kidney, cardiovascular, neurologic, gastrointestinal, blood, endocrine/metabolic, autoimmune or pulmonary disease, or untreated hypertension;
• Cancer of any kind (except basal cell) under treatment;
• Known or past coagulopathy conditions;
• Any medical conditions or medications on the AABB medical deferral list;
• Known HIV or acquired immunodeficiency syndrome-related illness or received a positive test result for HIV infection;
• Positive test for hepatitis B virus, hepatitis C virus, human T-cell lymphotropic virus (HTLV), West Nile virus, or syphilis;
• History of significant treated or untreated mental health issues;
• Female subject who is pregnant, lactating, or with a positive pregnancy test;
• Currently taking an antibiotic or another medication for an infection;
• Known intolerance to any components (biotin) in the investigational drug formulation;
• Systolic blood pressure \> 140 mm Hg;

Sponsors & Collaborators

• Vitalant Research Institute: lead
• University of Colorado, Denver: collaborator

Study Sites (2)

Anschutz Medical Center

Aurora, Colorado, 80045, United States

Location

Vitalant Research Institute

Denver, Colorado, 80230, United States

Location

Related Publications (2)

• Donnenberg AD, Kim-Shapiro DB, Kanias T, Moore LR, Kiss JE, Lee JS, Xiong Z, Wang L, Triulzi DJ, Gladwin MT. Optimizing interpretation of survival studies of fresh and aged transfused biotin-labeled RBCs. Transfusion. 2023 Jan;63(1):35-46. doi: 10.1111/trf.17192. Epub 2022 Dec 9.

  PMID: 36494878 BACKGROUND

• Mock DM, Stowell SR, Franco RS, Kyosseva SV, Nalbant D, Schmidt RL, Cress GA, Strauss RG, Cancelas JA, von Goetz M, North AK, Widness JA. Antibodies against biotin-labeled red blood cells can shorten posttransfusion survival. Transfusion. 2022 Apr;62(4):770-782. doi: 10.1111/trf.16849. Epub 2022 Mar 11.

  PMID: 35274303 BACKGROUND

Study Officials

• Philip Norris, MD

  Vitalant Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each participant will receive BioRBCs labeled with two different doses of biotin and stored for 6h and 24h.

Study Record Dates

• First Submitted: June 16, 2023
• First Posted: January 22, 2025
• Study Start: March 7, 2024
• Primary Completion: November 4, 2024
• Study Completion: November 4, 2024
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: At the end of the REDS-IV-P program, estimated in March 2026, the public use data sets will be available and will be available. The DCC will maintain a data archive for three years following the end of the REDS-IV-P contract (through March 21, 2029). At that point, data not on the NIH website will be destroyed.
• Access Criteria: Investigators can email the principal investigator to obtain access to the data and study protocol.

Locations

US (2)