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

Study Overview
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Brief Summary
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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.

Detailed Description
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The objective of this study is to assess effects of the storage of PRBC on pulmonary vasoconstriction measured as increase in pulmonary artery pressure and endothelial function measured as a change in reactive hyperemia index 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 parameters: Pulmonary vasoconstriction by trans-thoracic echocardiography Endothelium-mediated changes in vascular (arterial) tone, measured as reactive hyperemia index.

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

Conditions
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Blood Transfusion, Endothelial Physiopathology, Nitric Oxide, Pulmonary Hypertension

Intervention / Treatment
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* Procedure: Red blood Cells auto-transfusion
* Procedure: Red blood Cells auto-transfusion
* Drug: Inhaled Nitric Oxide (iNO) administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a photo ID Age>18 years old (required to provide informed consent) Age <60 years old Mild impairment of endothelial function, assessed by post ischemic vasodilation (L_RHI,<0.7) (38) Body mass index (BMI) >27 kg/m^2 and <40 kg/m^2 Fasting during the days of transfusion. Avoiding intake of high nitrate food (i.e. green leafy vegetables: lettuce, spinach) on the day prior to the study Feel well on the day of blood donation KG within normal limits Normotensive (systolic blood pressure <140 mmHg and diastolic <90 mmHg) Normal physical exam and blood test results as indicated by: WBC 4.5-11.0 n x103/μL HGB 12.0-17.5 gm/dl PLT 150-400 n x103/μL Plasma Sodium 135-145 mmol/L Plasma Potassium 3.4-4.8 mmol/L Plasma Chloride 98-108 mmol/L Plasma Carbon Dioxide 23.0-31.9 mmol/L Plasma Urea Nitrogen 8-25 mg/dl Plasma Creatinine 0.60-1.50 mg/dl Plasma Glucose 70-110 mg/dl Transaminase-SGPT 10-55 U/L Transaminase-SGOT 10-40 U/L Total Bilirubin < 2 mg/dl Fasting plasma glucose < 110 mg/dl Methemoglobin < 3% Exclusion Criteria: Psychiatric disturbances such as anxiety, depression, schizophrenia requiring pharmacological treatment or hospitalization in the last year Systemic disease with or without any functional limitation Pregnancy determined by urine pregnancy test, detecting presence of human chorionic gonadotropin (hCG), or less than six weeks postpartum Active smoking. Volunteers may be enrolled if they quit smoking for more than 1 year. Excess alcohol use: more than ½ L/day of wine consumption or equivalent Any current use of a medication other than: over-the-counter oral medications, herbal remedies, nutritional supplements, and oral contraceptives. Antibiotic use within 48 hours of blood donation Use of NSAIDS, corticosteroids, aspirin during the past 7 days Dental work within 24 hours prior to the donation Received or donated blood in the last 4 months Have had any forms of cancer with the exceptions of basal cell skin cancer or treatment for in situ uterine cervical cancer Currently enrolled in another research study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fresh blood<br> | Procedure: Red blood Cells auto-transfusion<br>* Withdrawal from 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 3 days storage time. The same 14 subjects will be included in every arm of the study.<br>|
| Experimental: Old blood<br> | Procedure: Red blood Cells auto-transfusion<br>* Withdrawal from the same 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 40 days storage time.<br>|
| Experimental: Old blood + inhaled Nitric Oxide<br> | Procedure: Red blood Cells auto-transfusion<br>* Withdrawal from the same 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 40 days storage time.<br>Drug: Inhaled Nitric Oxide (iNO) administration<br>* Subjects will breath iNO (80ppm) for 10 minutes before, during and for one hour after the autologous old-blood transfusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Pulmonary Artery Pressure | Pulmonary vasoconstriction was measured by estimation of Systolic Pulmonary Artery Pressure in millimeter of mercury (mmHg) by trans-thoracic echocardiography | Post-transfusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Function: Reactive Hyperemia Index | Reactive Hyperemia Index (RHI) measures Endothelial function and is assessed by digital pulse amplitude tonometry and it is a sensitive indicator of endothelial function. RHI is a calculated as a ratio between tested versus contralateral finger dilatation, thus there is no unit measure. | Post-transfusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemoglobins, Blood Transfusion, Autologous, Blood Preservation/adverse effects, Blood Transfusion/adverse effects, Endothelium, Vascular/physiopathology, Nitric Oxide, Pulmonary Hypertension