Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide (NO) Homeostasis

April 10, 2015 updated by: Mark Gladwin

The purpose of this study is to explore the impact of aged blood on endothelial function by measuring forearm blood flow during intra-arterial acetylcholine infusion in normal healthy human volunteers after infusion of autologous blood stored for 5-10 days or 35-42 days.

Our hypothesis is that 1) the vasodilatory response to the infusion of acetylcholine will be reduced in the 35-42 day group compared with the 5-10 day group, because of scavenging of the NO released from the endothelium by the hemolytic process in the aged blood, 2) that the infusion of aged stored blood will produce vasoconstriction, measured by reduced forearm blood flow during infusion of the 35-42 day compared with the 5-10 day old blood, and that 3) there will be increases in venous levels of cell free plasma hemoglobin, red cell microparticles, red cell membrane damage, arginase levels and activity, decreased arginine levels, markers of oxidative stress (carbamylated proteins and nitrated tyrosine residues), and increases in plasma in vitro NO consumption during the infusion of 35-42 day old compared to 5-10 day old blood.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The increased storage time of transfused blood is associated with an increased risk of cardiovascular events and organ failure. The underlying biological mechanism as to why this happens is not understood. A major abnormality in aged blood is the reduced life span of red blood cells after they are infused. This is associated with rupture of the red blood cells and release of their contents. However, the degree of red blood cell rupture and release of the cell's contents in humans after transfusion has not been well studied. It has been seen that even low levels of red blood cell rupture severely decrease the amount of nitric oxide and other factors that effect how blood vessels function. The purpose of this study is to perform human forearm blood flow studies to evaluate wether there are a sufficient amount these factors released during red blood transfusion to significantly affect how blood vessel function in humans.

This study will enroll normal healthy volunteers between 18 to 50 years of age. 500 ml (1.0 unit) of blood will be collected from subjects who will then return in 5-10 days and be re-infused with the blood 5-10 days after storage.The subjects will return after 25-37 days and be infused with blood 35-42 days after storage. The study will use a tool called strain gauge plethysmography and the drug acetylcholine to measure the effect of fresh (i.e., 5-10 days) versus aged (35-42 days) autologous blood transfusions on forearm blood flow in healthy volunteers.

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female and 18 to 50 years of age.
  • Able to read and comprehend the English language

Exclusion Criteria:

  • Less than 18 or greater than 50 years of age.
  • Female < 110 lbs or 50 kg
  • Male < 110 lbs or 50 kg
  • Hemoglobin <12.5g/dl
  • Past medical history or symptoms of blood dyscrasia, diabetes mellitus, hyperlipidemia, obstructive sleep apnea, hypertension, significant cardiac disease and / or known peripheral arterial disease.
  • History of cigarette smoking within the last month
  • Serum creatinine >1.0 mg/dL
  • Cognitively impaired subjects, or institutionalized persons and subjects unable or unwilling to complete written informed consent (no proxy consent will be obtained)
  • Subjects with a history of blood donation within the last 60 days.
  • Subjects who have performed other medical studies involving drug delivery in the last 30 days.
  • Subjects with an oxygen saturation value < 92%.
  • Any STATIN drug (Fluvastatin, Lovastatin, Pravastatin, Simvastatin, Rosuvastatin) currently or in the 4 weeks prior to the screening day
  • Any medication for the treatment of diabetes including oral hypoglycemics or insulin
  • lab tests indicating blood dyscrasia, diabetes, hypertension or hypercholesterolemia.Females of childbearing potential who are pregnant or unwilling to undergo pregnancy testing; females with positive pregnancy testing on screening day will be excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Acetylcholine and Blood
This is single arm study. Acetylcholine and blood is infused in brachial artery of non-dominant arm. Blood flow
Drug: Acetylcholine and Blood
The Acetylcholine solution will be infused intra-arterially at the dosage of 7.5 ug/min for 3 minutes, then 15ug/min for 3 minutes, then 30 ug/min for 3 minutes, after the infusion of normal saline. It will then be infused at 7.5ug/min for 3 minutes, followed by 15ug/min for 3 minutes, followed by 30 ug/min for 3 minutes after the infusion of autologous blood. This will be performed at 5-10 days and 35-42 days of blood storage time.
Other Names:
  • Miochol
  • Miochol-e

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood flow response to Acetylcholine.
Time Frame: 5-10 days vs 35-42 days
The primary endpoint will be a comparison of the blood flow responses to the acetylcholine after infusion of 5-10 day old blood compared with the responses after infusion of 35-42 day old blood, each controlled for the opposite arm.
5-10 days vs 35-42 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in blood flow response to fresh blood (5-10 days) in comparison to aged blood.
Time Frame: 5-10 days vs 35-42 days
A comparison of the change in blood flow responses at baseline and after infusion of 5-10 day old blood compared with the responses during infusion of 35-42 day old blood, each controlled for the opposite arm.
5-10 days vs 35-42 days
Comparison in the levels of various biomarkers of aged blood will be examined in venous blood collected from the antecubital vein during the infusion of 5-10 days versus35-42 days old autologous blood.
Time Frame: 5-10 days versus 35-42 days
5-10 days versus 35-42 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mark Gladwin

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Mark T Gladwin, M.D, University of Pittsburgh and University of Pittsburgh Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

June 3, 2010

First Submitted That Met QC Criteria

June 3, 2010

First Posted (Estimate)

June 4, 2010

Study Record Updates

Last Update Posted (Estimate)

April 14, 2015

Last Update Submitted That Met QC Criteria

April 10, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 686
  • R01HL098032-01 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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