Back to resultsPilot Study About the Harmful Effects of Blood Storage on Overweight People and the Role of iNO in This Setting
Primary Purpose
Blood Transfusion, Endothelial Physiopathology, Nitric Oxide
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Red blood Cells auto-transfusion
Red blood Cells auto-transfusion
Inhaled Nitric Oxide (iNO) administration
Sponsored by
About this trial
This is an interventional basic science trial for Blood Transfusion focused on measuring Blood Transfusion, Autologous, Blood Preservation/adverse effects, Blood Transfusion/adverse effects, Endothelium, Vascular/physiopathology, Hemoglobins, Nitric Oxide, Pulmonary Hypertension
Eligibility Criteria
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
Sites / Locations
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Fresh blood
Old blood
Old blood + inhaled Nitric Oxide
Arm Description
Outcomes
Primary Outcome Measures
Systolic Pulmonary Artery Pressure
Pulmonary vasoconstriction was measured by estimation of Systolic Pulmonary Artery Pressure in millimeter of mercury (mmHg) by trans-thoracic echocardiography
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT01529502
First Posted
February 6, 2012
Last Updated
April 17, 2017
Sponsor
Massachusetts General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01529502
Brief Title
Pilot Study About the Harmful Effects of Blood Storage on Overweight People and the Role of iNO in This Setting
Official Title
Effects of Stored Red Blood Cell Transfusion in Overweight Subjects With Endothelial Dysfunction: Influence of Inhaled Nitric Oxide (iNO)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blood Transfusion, Endothelial Physiopathology, Nitric Oxide, Pulmonary Hypertension
Keywords
Blood Transfusion, Autologous, Blood Preservation/adverse effects, Blood Transfusion/adverse effects, Endothelium, Vascular/physiopathology, Hemoglobins, Nitric Oxide, Pulmonary Hypertension
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fresh blood
Arm Type
Experimental
Arm Title
Old blood
Arm Type
Experimental
Arm Title
Old blood + inhaled Nitric Oxide
Arm Type
Experimental
Intervention Type
Procedure
Intervention Name(s)
Red blood Cells auto-transfusion
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Red blood Cells auto-transfusion
Intervention Description
Withdrawal from the same 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 40 days storage time.
Intervention Type
Drug
Intervention Name(s)
Inhaled Nitric Oxide (iNO) administration
Intervention Description
Subjects will breath iNO (80ppm) for 10 minutes before, during and for one hour after the autologous old-blood transfusion.
Primary Outcome Measure Information:
Title
Systolic Pulmonary Artery Pressure
Description
Pulmonary vasoconstriction was measured by estimation of Systolic Pulmonary Artery Pressure in millimeter of mercury (mmHg) by trans-thoracic echocardiography
Time Frame
Post-transfusion
Secondary Outcome Measure Information:
Title
Endothelial Function: Reactive Hyperemia Index
Description
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.
Time Frame
Post-transfusion
Other Pre-specified Outcome Measures:
Title
Hemolysis
Description
To assess concentration of plasma Hemoglobin at baseline, 10 minutes after blood transfusion, 1 hour after blood transfusion, 2 hours after blood transfusion and 4 hours after blood transfusion.
Time Frame
before and after blood transfusion
Title
Nitric Oxide Metabolites
Description
To assess concentration of plasma Nitric oxide metabolites at baseline, 10 minutes after blood transfusion, 1 hour after blood transfusion, 2 hours after blood transfusion and 4 hours after blood transfusion.
Time Frame
Before and after blood transfusion
Title
Concentration of Cytokines
Description
To assess concentration of plasma cytokines at baseline, 10 minutes after blood transfusion, 1 hour after blood transfusion, 2 hours after blood transfusion and 4 hours after blood transfusion.
Time Frame
Before and after blood transfusion
Title
Activation of Platelets
Description
To assess concentration of plasma activation of platelets at baseline, 10 minutes after blood transfusion, 1 hour after blood transfusion, 2 hours after blood transfusion and 4 hours after blood transfusion.
Time Frame
Before and after blood transfusion
Title
Activation of Inflammatory Lipid Mediators
Description
To assess concentration of plasma activation of inflammatory lipid mediators at baseline, 10 minutes after blood transfusion, 1 hour after blood transfusion, 2 hours after blood transfusion and 4 hours after blood transfusion.
Time Frame
Before and after blood transfusion
Title
Changes in Gene Expression
Description
To assess concentration of changes in gene expression at baseline, 10 minutes after blood transfusion, 1 hour after blood transfusion, 2 hours after blood transfusion and 4 hours after blood transfusion.
Time Frame
Before and after blood transfusion
Title
Endothelial Function
Description
To assess Endothelial function by RHI at baseline, 10 minutes after blood transfusion, 1 hour after blood transfusion, 2 hours after blood transfusion and 4 hours after blood transfusion.
Time Frame
Before and after blood transfusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Warren Zapol, MD
Organizational Affiliation
Masachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
19224780
Citation
Hendrickson JE, Hillyer CD. Noninfectious serious hazards of transfusion. Anesth Analg. 2009 Mar;108(3):759-69. doi: 10.1213/ane.0b013e3181930a6e.
Results Reference
background
PubMed Identifier
18354101
Citation
Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, Blackstone EH. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008 Mar 20;358(12):1229-39. doi: 10.1056/NEJMoa070403.
Results Reference
background
PubMed Identifier
17940021
Citation
Bennett-Guerrero E, Veldman TH, Doctor A, Telen MJ, Ortel TL, Reid TS, Mulherin MA, Zhu H, Buck RD, Califf RM, McMahon TJ. Evolution of adverse changes in stored RBCs. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17063-8. doi: 10.1073/pnas.0708160104. Epub 2007 Oct 11.
Results Reference
background
PubMed Identifier
10856270
Citation
Cardillo C, Kilcoyne CM, Cannon RO 3rd, Panza JA. Interactions between nitric oxide and endothelin in the regulation of vascular tone of human resistance vessels in vivo. Hypertension. 2000 Jun;35(6):1237-41. doi: 10.1161/01.hyp.35.6.1237.
Results Reference
background
PubMed Identifier
8491001
Citation
Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA. Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation. 1993 May;87(5):1468-74. doi: 10.1161/01.cir.87.5.1468.
Results Reference
background
PubMed Identifier
22021369
Citation
Hod EA, Brittenham GM, Billote GB, Francis RO, Ginzburg YZ, Hendrickson JE, Jhang J, Schwartz J, Sharma S, Sheth S, Sireci AN, Stephens HL, Stotler BA, Wojczyk BS, Zimring JC, Spitalnik SL. Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron. Blood. 2011 Dec 15;118(25):6675-82. doi: 10.1182/blood-2011-08-371849. Epub 2011 Oct 20.
Results Reference
background
PubMed Identifier
25162920
Citation
Berra L, Pinciroli R, Stowell CP, Wang L, Yu B, Fernandez BO, Feelisch M, Mietto C, Hod EA, Chipman D, Scherrer-Crosbie M, Bloch KD, Zapol WM. Autologous transfusion of stored red blood cells increases pulmonary artery pressure. Am J Respir Crit Care Med. 2014 Oct 1;190(7):800-7. doi: 10.1164/rccm.201405-0850OC.
Results Reference
derived
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Pilot Study About the Harmful Effects of Blood Storage on Overweight People and the Role of iNO in This Setting
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