Pilot Study About the Harmful Effects of Blood Storage on Overweight People and the Role of iNO in This Setting

Inflammation Clinical Trial

Official title: Effects of Stored Red Blood Cell Transfusion in Overweight Subjects With Endothelial Dysfunction: Influence of Inhaled Nitric Oxide (iNO)

Status Completed

Clinical Trial Summary

The purpose of this study is to determine whether storage time affects how human body responds to autologous blood transfusion. An autologous blood transfusion is when a person donates blood and then receives that same blood back in the transfusion. We also want to find out if in this situation inhaled nitric oxide can help to prevent the potential reduction of vasodilation capacity. Vasodilation capacity is the ability of the blood vessel to widen when needed.

Clinical Trial Description

The objective of this study is to assess effects of the storage of PRBC on endothelial function, inflammation and platelet activation in overweight people with existing endothelial dysfunction at baseline.

The present study consists of three different parts, which will be scheduled in a randomized order on the same subject (crossover study).

During one phase of the study, 14 healthy human volunteers will donate a unit of Packed Red Blood Cells (PRBC), which will be leukoreduced and stored in Additive Solutions-1 (AS-1), and then transfused back to the subjects after 3 days of storage at 4º C in the MGH Blood Bank (Fresh Blood arm). The second part of the study consists in the collection of another unit of PRBC from the same volunteers which will be transfused back to them after 40 days of storage (Old Blood arm). Finally in the third part, like in the second one, one unit of PRBC will be withdraw and stored for 40 days, but 80 ppm (parts per million by volume) Nitric Oxide in air will be administered together with the transfusion. There will be a 2 weeks interval after each PRBC transfusion.

We hypothesize that old red blood cells stored under conventional conditions may trigger a complex, pro-inflammatory, pro-thrombotic and vasoconstriction response. We will compare the response to PRBC stored for 3 days with the response to PRBC stored for 40 days in the same healthy volunteers. We also want to test the hypothesis that inhaled nitric oxide may reverse these adverse effects.

We will monitor/measure the following markers/parameters:

1. Endothelium-mediated changes in vascular (arterial) tone

2. Tissue oxygen saturation will be continuously assessed during and after blood transfusion

3. Hemolysis as quantified by changes in plasma haptoglobin level, plasma free hemoglobin, LDH level, bilirubin level, iron level, ferritin, and transferrin

4. Changes of plasma and red blood cell levels of circulating nitrate, nitrite, RXNO, RNNO, NO-heme

5. Concentration of cytokines, such as IL-6, IL-8, IL-10, IL-12, TNF, IFN-γ

6. Activation of platelets through circulating P-selectin expression on platelets

7. Activation of inflammatory lipid mediators

8. Changes in gene expression profiling analyzing RNA microarray of circulating leukocytes ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Blood Transfusion
• Endothelial Physiopathology
• Hemoglobins
• Inflammation
• Nitric Oxide

• NCT number: NCT01529502
• Study type: Interventional
• Source: Massachusetts General Hospital
• Status: Completed
• Phase: Phase 2
• Start date: March 2012
• Completion date: December 2013