Adverse Effects of RBC Transfusions: A Unifying Hypothesis (INOBA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John D Roback, Emory University
ClinicalTrials.gov Identifier:
NCT00838331
First received: February 5, 2009
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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). We are trying to determine the nature of these substances in human beings when they are transfused "aged" versus "fresh" red blood cells. It is our 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. This study is also designed to test the effects of transfusing "aged" versus "fresh" red blood cells in volunteers with traditional cardiovascular risk factors (high blood pressure, diabetes, high cholesterol, and tobacco use) on 1) the degree of relaxation in the arteries and subsequent changes in blood flow, 2) blood levels of oxidant molecules, 3) inflammation, and 4) stem cells.

There is evidence that red blood cells produce NO, which normally causes arteries to relax and increase blood supply. We 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 our 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.


Condition Intervention Phase
Cardiovascular Diseases
Blood Transfusion
Biological: Fresh blood
Biological: Aged blood
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adverse Effects of RBC Transfusions: A Unifying Hypothesis

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • To investigate the effects of blood processing and storage (using standard FDA-approved conditions) on NO production and scavenging by human RBCs/Hb in vitro. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To transfuse healthy volunteers and investigate the effects of storage-related RBC changes on blood flow, tissue oxygenation, and biomarkers of cardiovascular function. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • To determine the effects of transfused RBCs in patients with endothelial dysfunction due to cardiovascular disease. [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: April 2009
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fresh blood Biological: Fresh blood
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.
Experimental: Aged blood Biological: Aged blood
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.

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  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male or female volunteers (age 21-60 years) and subjects with greater than two cardiovascular risk factors (hypercholesterolemia, diabetes, hypertension, and tobacco smoking) or known cardiovascular disease will be invited to participate in the study.
  • Healthy subjects: Healthy male or female volunteers (aged 21-60 years).
  • Hypercholesterolemia: Defined as serum low density lipoprotein cholesterol > 140 mg/dL if not currently on lipid-lowering therapy or > 100 mg/dL if on lipid-lowering therapy.
  • Diabetes: Defined as having fasting blood glucose sample of > 126 mg/dL or a hemoglobin A1c of > 7% or being treated with diabetes medications such as oral hypoglycemic agents, insulin sensitizing agents, or subcutaneous insulin.

Patients with diabetes will be asked to hold their oral diabetes medications starting the evening before the study and withhold insulin injections starting the morning of the study.

  • Smoking: active tobacco use, 20 cigarettes per day for the past year.
  • Hypertension: Blood pressure of > 140/90 or currently on anti-hypertensive medications
  • Cardiovascular disease: known coronary artery disease by angiogram or documented myocardial infarction.

Exclusion Criteria:

  • Presence of intercurrent illness or other chronic diseases
  • Age <21 or > 80 years
  • Pregnancy or menopause
  • Renal failure (creatinine>1.4 mg/dl)
  • 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 Inability to return to Emory for follow-up
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00838331

Locations
United States, Georgia
Emory University
Atlanta, Georgia, United States
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Arshed A Quyyumi, MD Emory University
Principal Investigator: John Roback, MD, PhD Emory University
  More Information

No publications provided

Responsible Party: John D Roback, Professor, Emory University
ClinicalTrials.gov Identifier: NCT00838331     History of Changes
Other Study ID Numbers: IRB00015316
Study First Received: February 5, 2009
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 20, 2014