Adverse Effects of RBC Transfusions: A Unifying Hypothesis

NCT00838331 | Completed Phase 2 Results DMC

• 1 other identifier: IRB00015316
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Transfusion of red blood cells is often used in critically ill patients with low red blood cell counts to prevent disease progression and death. Recent studies suggest that the use of "aged" versus "fresh" red blood cells are associated with worse clinical outcomes. There is evidence that red blood cells work with the cells lining our blood vessels to produce a variety of substances that normally cause arteries to relax and increase blood supply. Two of these substances are called nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The investigators are trying to determine the nature of these substances in human beings when they are transfused "aged" versus "fresh" red blood cells. It is their thought that "aged" red blood cells have less of the substances (NO and EDHF) that naturally relax our arteries and further changes the blood supply. One way to determine this is to transfuse a subject's own "aged" and "fresh" red blood cells and inject substances such as L-NMMA (L-NG monomethyl arginine) and TEA (tetraethylammonium chloride), which block the production of NO and EDHF respectively, and then, study what happens to the blood flow. There is evidence that red blood cells produce NO, which normally causes arteries to relax and increase blood supply. The investigators will try to determine the nature of NO in red blood cells and whether the amount of this substance is altered because of different blood processing and storage techniques. It is their thought that "aged" red blood cells have less NO that naturally relaxes our arteries and further changes the blood supply. This study is designed to determine the most ideal way of storing and processing blood.

Conditions

Healthy Volunteers

Keywords

Blood Transfusions

Outcome Measures

Primary Outcomes (1)

• The Effects of Storage-related RBC Changes on Acetylcholine-stimulated (NO-mediated) Forearm Blood Flow.

  The primary outcome measures are changes in forearm blood flow (FBF) in recipients of fresh or stored RBC transfusions in response to acetylcholine. Secondary measures include changes in FBF with acetylcholine with or without L-NMMA, and changes in FBF with forearm exercise. In addition, flow mediated dilation (FMD) measurements will also be used to assess changes in brachial artery diameter before and after fresh vs aged RBC transfusions.

  5 years

Study Arms (1)

Fresh blood, then aged blood

EXPERIMENTAL

Biological: Fresh blood; Biological: Aged blood

Interventions

Fresh blood BIOLOGICAL

For fresh transfusions, a whole blood unit will be drawn from volunteers, processed, and then reinfused on the same day during the study. For impaired and repaired transfusions, the volunteers will be brought to the blood bank to donate; then, after processing and the appropriate length of storage (eg, 28 days), they will return for the FBF studies. Since recipients of fresh transfusions are relatively anemic after donation and before reinfusion, recipients of impaired/repaired transfusions should also be mildly anemic for the study. Thus, they will donate another whole blood unit prior to beginning the study course, they will be transfused with their stored unit during the study, and then the autologous unit collected at the beginning of the day will be reinfused at the end of the day after the study is complete.

Fresh blood, then aged blood

Aged blood BIOLOGICAL

In a separate aim, the FMD assay will be used to investigate NO-mediated vasodilation in patients with CVD who are receiving transfusions. Over 60% of blood orders for cardiology patients at Emory are for 2 units or more. Therefore, when a 2-unit order is placed on a consented patient, they will be issued both fresh (\< 7 days) and impaired (\> 28 days) compatible units from inventory. Prior to starting transfusions, the patient will be randomized to either receive the fresh or the older unit first. All RBC units will be ACD/AS1. Units will also be leukoreduced and/or irradiated, if either of those modifications were found to impair NO bioavailability in prior studies. If washing or rejuvenation were found to be successful in significantly "repairing" NO bioavailability in previous aims, some patients may also receive impaired and repaired (\> 28 days; washed or rejuvenated) RBC transfusions.

Fresh blood, then aged blood

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or female volunteers (age 21-60 years)
• Must meet guidelines for blood donors including:
• standard blood donor history questionnaire
• body weight of at least 110 lbs
• hemoglobin concentration of at least 12.5 gm/dL
• body temperature of no more than 99.5 oF
• pulse of 50-100 bpm
• blood pressure \< 180/100
• test negative for the standard battery of blood donor screening tests (anti-HIV, HIV RNA, anti-HCV, HCV RNA, HBsAg, anti-HBc, anti-HTLV-I/II, and WNV RNA)
• Aim 1:

You may not qualify if:

• Failure to pass the blood donor history questionnaire
• Positive results on the standard battery of blood donor screening tests
• Failure to meet criteria for donation
• Aim 2:
• Healthy male or female volunteers (age 21-80 years)
• Presence of intercurrent illness or other chronic diseases
• Renal failure (creatinine\>1.4 mg/dl)
• Pregnancy
• Allergies to aspirin
• Bleeding disorders
• Uncontrolled hypertension with BP \> 180 mmHg systolic and \> 120 mmHg diastolic
• Acute infection in previous 4 weeks
• History of substance abuse
• Liver failure (Liver enzymes \>2x normal)
• Inability to give informed consent

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (2)

• Hayek SS, Neuman R, Ashraf K, Sher S, Newman JL, Karatela S, Roback JD, Quyyumi AA. Effect of storage-aged red blood cell transfusions on endothelial function in healthy subjects. Transfusion. 2015 Nov;55(11):2768-70. doi: 10.1111/trf.13276. No abstract available.

  PMID: 26559401 DERIVED

• Neuman R, Hayek S, Rahman A, Poole JC, Menon V, Sher S, Newman JL, Karatela S, Polhemus D, Lefer DJ, De Staercke C, Hooper C, Quyyumi AA, Roback JD. Effects of storage-aged red blood cell transfusions on endothelial function in hospitalized patients. Transfusion. 2015 Apr;55(4):782-90. doi: 10.1111/trf.12919. Epub 2014 Nov 13.

  PMID: 25393772 DERIVED

Limitations and Caveats

Primary limitation is that we are studying transfusion effects of fresh vs stored RBCs in healthy individuals, and not sick, anemic individuals as are often encountered in the hospital.

Results Point of Contact

• Title: John Roback, MD PhD
• Organization: Emory University

jroback@emory.edu

404-712-1774

Study Officials

• Arshed A Quyyumi, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• John Roback, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 5, 2009
• First Posted: February 6, 2009
• Study Start: April 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: October 1, 2013
• Last Updated: March 6, 2015
• Results First Posted: March 6, 2015

Record last verified: 2015-03

Locations

US (1)