Rejuvenated RBC and VO2 Max in Healthy Subjects

NCT03089047 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: Pro00078468
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

To compare the physiologic benefits of rejuvenated RBCs (rejRBCs) to standards RBCs (PRBCs), we will emulate critical conditions by safely maximizing stress on the cardiovascular system, in an elective, feasible volunteer study. Maximal oxygen uptake (VO2max) will be measured in an anemic, post-donation, pre-transfusion state, and also after transfusing 14-day-old, autologous blood randomized to standard storage or standard storage with rejuvenation. We hypothesize that transfusion of standard PRBCs is less effective at increasing oxygen delivery (measured by VO2max) compared with transfusion of rejRBCs.

Conditions

Erythrocyte Transfusion

Outcome Measures

Primary Outcomes (2)

• Change in VO2max

  Change in VO2max from "anemic" (pre-transfusion) VO2max and after transfusion of 2 units of either standard PRBCs or rej-PRBCs "post-Tx" VO2max.

  Day 16 to Day 18 post transfusion

• Change in Lactate

  Change in lactate from "anemic" (pre-transfusion) VO2max and after transfusion of 2 units of either standard PRBCs or rej-PRBCs "post-Tx" VO2max

  Day 16 to Day 18 post transfusion

Secondary Outcomes (1)

• Change in "Post-Tx" VO2max From Baseline

  Baseline to Day 18 post transfusion

Study Arms (2)

Rejuvenated RBC Transfusion

EXPERIMENTAL

Washed and Rejuvenated autologous blood

Biological: Transfusion of rejuvenated and washed autolgous RBCs

Standard RBC Transfusion

SHAM COMPARATOR

Washed autologous blood (so as to maintain equivalent unit volume and Hct)

Biological: Transfusion of washed autolgous RBCs

Interventions

Transfusion of rejuvenated and washed autolgous RBCs BIOLOGICAL

Rejuvenation refers to the process of adding a mix of solutes (Rejuvesol®, Citra Labs, Braintree, MA; consists of sodium pyruvate, inosine, adenine, mono- and dibasic sodium phosphate) to older, stored (i.e., 2-3 DPG-depleted) blood to immediately restore 2,3-DPG and ATP levels in the stored red blood cells15. Rejuvenation was originally developed to prolong the storage life of rare-phenotype RBC units. It is FDA-approved for use in RBC units stored in CPD, CPDA-1, and AS-1. The major contraindication for the use of Rejuvesol® is in RBC units stored for fewer than 6 days due to high baseline 2,3-DPG and ATP levels. Rejuvenated units must be washed prior to administration to remove residual Rejuvesol that is not approved for iv administration in such concentrations.

Rejuvenated RBC Transfusion

Transfusion of washed autolgous RBCs BIOLOGICAL

Autologous RBCs will be washed prior to transfusion to maintain blinding and equalize volume and Hct with the rejuvenated and washed intervention arm

Standard RBC Transfusion

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female
• Age 18-40 (the American College of Sports Medicine Guidelines for Exercise Testing defines this age group with no or no more than one coronary heart disease risk factor as low-risk for VO2 max testing)
• Habitual exerciser defined as ≥ 30 minutes of at least moderate or high intensity exercise ≥ 3 times per week. After consent, and at the subsequent screening visit, a VO2 max test will be performed, and subjects with a low value (\< 35 mL/kg/min) will be excluded (screen failure). Based on our previous experience, we anticipate that up to 25% of the subjects will fall into this category; therefore, 10 subjects will be screened to obtain 6-8 participants who go on to donate their blood.
• Calculated total blood volume of at least 4,500 mL using an established formula:
• Men: (0.006012 x H3) + (14.6 x W) + 604 = TBV
• Women: (0.005835 x H3) + (15 x W) + 183 = TBV \[H= Height in inches; W=Weight in pounds\]
• Has access to transportation to visit the blood collection facility and to return to Duke for all study visits
• Weighs at least 130 pounds

You may not qualify if:

• Any significant acute or chronic medical illness or problem, including, but not limited to, diabetes, hypertension, cardiac disease, asthma, COPD
• Current or recent (last 60 days) tobacco or nicotine use
• History of sickle cell trait or disease or any other acquired or hereditary hematological abnormality
• History of fainting or other significant adverse reaction during phlebotomy or donation of blood
• Known prolonged QTc (or evidence of such at screening) defined as QTc \>470 ms
• Known or suspected illicit drug or alcohol abuse
• Known or suspected HIV, Hepatitis B, or Hepatitis C infection
• History of thrombophilia or anticoagulant therapy
• Pregnancy
• Obesity defined as BMI\>30
• Recent history of blood donation:
• Single whole blood unit donation within the past 8 weeks
• Double RBC donation by apheresis within the past 16 weeks
• Plasma donation by apheresis within the past 4 weeks
• Inadequate red blood cell mass evidenced by total blood volume \<4500 mL (above) or screening hemoglobin \<13.3 g/dL

Sponsors & Collaborators

• Duke University: lead
• Zimmer Biomet: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27514, United States

Location

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Ian Welsby, M.D.
• Organization: Duke University

ian.welsby@duke.edu

919-681-6752

Study Officials

• Ian J Welsby, BSc MBBS

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Addition of rejuvesol will be performed by the blood bank and only they will know of group assignment
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective randomized "healthy volunteer" study

Study Record Dates

• First Submitted: March 20, 2017
• First Posted: March 24, 2017
• Study Start: September 29, 2017
• Primary Completion: April 18, 2018
• Study Completion: April 18, 2018
• Last Updated: January 11, 2021
• Results First Posted: January 11, 2021

Record last verified: 2020-12

Locations

US (1)