Measuring Red Blood Cell Survival After TransfusionEarly Phase 1NCT06788080
Optimization of Biotinylation Protocol for Studies of Red Blood Cell Survival and Function After Transfusion
A Early Phase 1 study testing BioRBC in people with Measuring Red Blood Cell Survival After Transfusion, run by Vitalant Research Institute at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Measuring Red Blood Cell Survival After Transfusion
- What is being tested?
- BioRBC
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 7 Mar 2024to 4 Nov 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 23Show fewer
- 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;
- Diastolic blood pressure > 90 mm Hg;
- Temperature > 100°F;
- Known hemoglobin <13 for male donors and <12.5 for female donors;
- Positive direct antiglobulin test (DAT);
- Treatment with any investigational agent within 1 month before treatment infusion for this trial;
- Unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's return for follow-up visits on schedule;
- Other unspecified reasons that, in the opinion of the investigator, make the subject unsuitable for enrollment;
- Institutionalized because of legal or regulatory order
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Anschutz Medical Center
Aurora, Colorado, 80045
Vitalant Research Institute
Denver, Colorado, 80230
About this study
Official title: Optimization of Biotinylation Protocol for Next Generation Studies of Red Blood Cell Survival and Function After Transfusion
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:
- Screening visit, collect 35 ml blood, about 3 tablespoons
- Donate 500 ml blood
- Receive 20 ml of biotin labeled blood transfusion, collect 40 ml blood, about 3 tablespoons
- Return 1 day after transfusion for blood draw (25 ml, about 2 tablespoons)
- Return 30 days after transfusion for blood draw (25 ml, about 2 tablespoons)
- Return 90 days after transfusion for blood draw (25 ml, about 2 tablespoons)
Read the detailed description
The objective of this open label, pilot, single center, trial of biotinylated red blood cells (BioRBCs) is to determine the impact of RBC biotinylation timing (48h vs 6h prior to transfusion) on autologous BioRBCs posttransfusion recovery in 12 healthy subjects. The rationale is to determine the feasibility of manufacturing BioRBC at a central site that is remote from the site of the clinical study, where transfusion occurs. Manufacturing and transportation will result in a delayed (up to 48 hrs.) transfusion of the BioRBCs. In this trial each subject will donate one unit of autologous whole blood which will be manufactured into leukoreduced packed RBCs (pRBCs) in additive solution-1 (AS-1) and stored for 42 days. Biotin labelling of the pRBCs will occur at 2 different time points, after 35-40 days of storage or after 37-42 days of storage with 2 different doses of biotin (3 µg/mL vs 15 µg/mL). Subjects will be stratified at the time of enrollment (first 6 subjects enrolled vs last 6 subjects enrolled) to a labelling sequence related to both the dose of biotin label and the time of labelling. The stratification sequence is defined by subjects with an earlier enrollment (first 6 subjects enrolled) who will have low dose biotin label (3µg/mL) after storage of autologous pRBCs at the earlier time point (35-40 days), and the high dose biotin label (15µg/mL) after storage of autologous pRBCs at the later time point (37-42 days). The alternative labelling procedure, for subjects enrolled later on study (last 6 subjects enrolled), will utilize the high dose biotin label (15 µg/mL) after storage of autologous pRBCs at the earlier time point (35-40 days) and the low dose biotin label (3µg/mL) after storage of autologous pRBCs at the later time point (37-42 days).
This stratification is designed to result in the second biotin labelling to occur on the day of transfusion (which is also approximately 2 days after the first biotinylation process). Thus, each subject will receive a total of two sequential 10 mL doses of BioRBCs during one infusion visit.
- Being tested
- BioRBC
- Keywords
- Biotin, Red blood cell, Transfusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BioRBCDrug
Autologous biotin-labeled RBCs will be transfused to study participants
| Study group | Role | What they receive |
|---|---|---|
| BioRBC arm | Experimental | Each subject will receive biotin labeled red blood cells stored for 6 hours and 24 hours (two separate aliquots infused sequentially). Receives: Drug: BioRBC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours after transfusion
Secondary outcomes (4)
Percent BioRBC recovery
The percentage 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.
Measured: 10 min, 30 min, 1 hour, 30 days, and 90 days after transfusion
Number of participants who form BioRBC antibodies
Test for the presence of antibodies directed against BioRBCs using a gel card assay. Results will be positive or negative, and we will track the number of participants with positive results.
Measured: Pre-transfusion and 1, 30, and 90 days after transfusion
Percent of cells with BioRBC oxidative stress
Measure BioRBC oxidative stress by staining cells with BODIPY. Results will be expressed as the percentage of BODIPY+ BioRBCs in each participant. BODIYP+ BioRBCs will be compared between BioRBCs labeled at 6 vs. 48 hours.
Measured: 10 min, 30 min, 1 hour, 1 day, 30 days, and 90 days after transfusion
Percent of BioRBCs expressing phosphatidyl serine
Measure BioRBC phosphatidyl serine expression, which will be measured as the percentage of BioRBCs that bindannexin V, assessed by flow cytometry. Annexin V+ BioRBCs will be compared between BioRBCs labeled at 6 vs. 48 hours.
Measured: 10 min, 30 min, 1 hour, 1 day, 30 days, and 90 days after transfusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2025
- Study start7 Mar 2024
- Primary completion4 Nov 2024
- Study completion4 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Measuring Red Blood Cell Survival After TransfusionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Each participant will receive BioRBCs labeled with two different doses of biotin and stored for 6h and 24h.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vitalant Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of Colorado, Denver
- Responsible party
- Sponsor
- Investigators
- Philip Norris, MD, Principal investigator, Vitalant Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06788080
- Sponsor's protocol ID
- 11735-01
- Status last verified
- Jan 2025
- First submitted
- 16 Jun 2023
- Last updated
- 22 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: A de-identified study dataset will be submitted to Westat, the Data Coordinating Center (DCC) for the REDS-IV-P program. Study outcomes (post-transfusion RBC recovery, BioRBC antibody status, and annexin V and RBC redox state will be outcomes reported). The DCC will create public use datasets and deliver them to NHLBI at the end of the study (and end of the REDS-IV-P program).
Publications
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.
PubMed 36494878Mock 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.
PubMed 35274303
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of Biotinylation Protocol for Next Generation Studies of Red Blood Cell Survival and Function After Transfusion
- ClinicalTrials.gov ID
- NCT06788080
- Acronym / sponsor ID
- 11735-01
- Keywords
- Biotin, Red blood cell, Transfusion
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Vitalant Research InstituteUniversity, hospital or other
- Collaborators
- University of Colorado, Denver
- Study start
- 7 Mar 2024 (actual)
- Primary completion
- 4 Nov 2024 (actual)
- Study completion
- 4 Nov 2024 (actual)
- First posted
- 22 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Screening visit, collect 35 ml blood, about 3 tablespoons
- Donate 500 ml blood
- Receive 20 ml of biotin labeled blood transfusion, collect 40 ml blood, about 3 tablespoons
- Return 1 day after transfusion for blood draw (25 ml, about 2 tablespoons)
- Return 30 days after transfusion for blood draw (25 ml, about 2 tablespoons)
- Return 90 days after transfusion for blood draw (25 ml, about 2 tablespoons)
Detailed description
The objective of this open label, pilot, single center, trial of biotinylated red blood cells (BioRBCs) is to determine the impact of RBC biotinylation timing (48h vs 6h prior to transfusion) on autologous BioRBCs posttransfusion recovery in 12 healthy subjects. The rationale is to determine the feasibility of manufacturing BioRBC at a central site that is remote from the site of the clinical study, where transfusion occurs. Manufacturing and transportation will result in a delayed (up to 48 hrs.) transfusion of the BioRBCs. In this trial each subject will donate one unit of autologous whole blood which will be manufactured into leukoreduced packed RBCs (pRBCs) in additive solution-1 (AS-1) and stored for 42 days. Biotin labelling of the pRBCs will occur at 2 different time points, after 35-40 days of storage or after 37-42 days of storage with 2 different doses of biotin (3 µg/mL vs 15 µg/mL). Subjects will be stratified at the time of enrollment (first 6 subjects enrolled vs last 6 subjects enrolled) to a labelling sequence related to both the dose of biotin label and the time of labelling. The stratification sequence is defined by subjects with an earlier enrollment (first 6 subjects enrolled) who will have low dose biotin label (3µg/mL) after storage of autologous pRBCs at the earlier time point (35-40 days), and the high dose biotin label (15µg/mL) after storage of autologous pRBCs at the later time point (37-42 days). The alternative labelling procedure, for subjects enrolled later on study (last 6 subjects enrolled), will utilize the high dose biotin label (15 µg/mL) after storage of autologous pRBCs at the earlier time point (35-40 days) and the low dose biotin label (3µg/mL) after storage of autologous pRBCs at the later time point (37-42 days).
This stratification is designed to result in the second biotin labelling to occur on the day of transfusion (which is also approximately 2 days after the first biotinylation process). Thus, each subject will receive a total of two sequential 10 mL doses of BioRBCs during one infusion visit.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Each participant will receive BioRBCs labeled with two different doses of biotin and stored for 6h and 24h.
| Arm | Type | Receives |
|---|---|---|
| BioRBC arm | Experimental | Drug: BioRBCEach subject will receive biotin labeled red blood cells stored for 6 hours and 24 hours (two separate aliquots infused sequentially). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (23 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BioRBCAutologous biotin-labeled RBCs will be transfused to study participants | Drug | BioRBC arm |
Primary outcome
Percent BioRBC recovery
Time frame: 24 hours after transfusion
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.
4 secondary outcomes
Percent BioRBC recovery
Time frame: 10 min, 30 min, 1 hour, 30 days, and 90 days after transfusion
Number of participants who form BioRBC antibodies
Time frame: Pre-transfusion and 1, 30, and 90 days after transfusion
Percent of cells with BioRBC oxidative stress
Time frame: 10 min, 30 min, 1 hour, 1 day, 30 days, and 90 days after transfusion
Percent of BioRBCs expressing phosphatidyl serine
Time frame: 10 min, 30 min, 1 hour, 1 day, 30 days, and 90 days after transfusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2025.
- Background: PubMed 36494878Donnenberg 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.
- Background: PubMed 35274303Mock 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.
- Individual participant dataSharing planned: Yes. A de-identified study dataset will be submitted to Westat, the Data Coordinating Center (DCC) for the REDS-IV-P program. Study outcomes (post-transfusion RBC recovery, BioRBC antibody status, and annexin V and RBC redox state will be outcomes reported). The DCC will create public use datasets and deliver them to NHLBI at the end of the study (and end of the REDS-IV-P program).
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip Norris, MD principal investigator
Vitalant Research Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing BioRBC in people with Measuring Red Blood Cell Survival After Transfusion, run by Vitalant Research Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent BioRBC recovery (time frame: 24 hours after transfusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06788080, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2025.