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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Warren M. Zapol, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01529502
First received: February 6, 2012
Last updated: February 8, 2017
Last verified: February 2017

February 6, 2012
February 8, 2017
March 2012
December 2013   (Final data collection date for primary outcome measure)
Systolic Pulmonary Artery Pressure [ Time Frame: Post-transfusion ]
Pulmonary vasoconstriction was measured by estimation of Systolic Pulmonary Artery Pressure in millimeter of mercury (mmHg) by trans-thoracic echocardiography
  • Endothelial Function [ Time Frame: Baseline ]
  • Endothelial Function [ Time Frame: 10 min after transfusion ]
  • Endothelial function [ Time Frame: 1h after transfusion ]
  • Endothelial Function [ Time Frame: 4h after transfusion ]
Complete list of historical versions of study NCT01529502 on ClinicalTrials.gov Archive Site
Reactive Hyperemia Index [ Time Frame: Post-transfusion ]
Reactive Hyperemia Index (RHI) 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.
  • Hemolysis [ Time Frame: Baseline ]
  • Nitric Oxide metabolites [ Time Frame: Baseline ]
  • Concentration of cytokines [ Time Frame: Baseline ]
  • Activation of platelets [ Time Frame: Baseline ]
  • Activation of inflammatory lipid mediators [ Time Frame: Baseline ]
  • Changes in gene expression [ Time Frame: Baseline ]
  • Hemolysis [ Time Frame: 10 min after transfusion ]
  • Nitric Oxide Metabolites [ Time Frame: 10 min after transfusion ]
  • Concentration of cytokines [ Time Frame: 10 min after transfusion ]
  • Activation of platelets [ Time Frame: 10 min after transfusion ]
  • Activation of inflammatory lipid mediators [ Time Frame: 10 min after transfusion ]
  • Changes in gene expression [ Time Frame: 10 min after transfusion ]
  • Hemolysis [ Time Frame: 1h after transfusion ]
  • Nitric Oxide metabolites [ Time Frame: 1h after transfusion ]
  • Concentration of cytokines [ Time Frame: 1h after transfusion ]
  • Activation of platelets [ Time Frame: 1h after transfusion ]
  • Activation of inflammatory lipid mediators [ Time Frame: 1h after transfusion ]
  • Changes in gene expression [ Time Frame: 1h after transfusion ]
  • Hemolysis [ Time Frame: 2h after transfusion ]
  • Nitric Oxide metabolites [ Time Frame: 2h after transfusion ]
  • Concentration of cytokines [ Time Frame: 2h after transfusion ]
  • Activation of platelets [ Time Frame: 2h after transfusion ]
  • Activation of inflammatory lipid mediators [ Time Frame: 2h after transfusion ]
  • Changes in gene expression [ Time Frame: 2h after transfusion ]
  • Hemolysis [ Time Frame: 4h after transfusion ]
  • Nitric Oxide metabolites [ Time Frame: 4h after transfusion ]
  • Concentration of cytokines [ Time Frame: 4h after transfusion ]
  • Activation of platelets [ Time Frame: 4h after transfusion ]
  • Activation of inflammatory lipid mediators [ Time Frame: 4h after transfusion ]
  • Changes in gene expression [ Time Frame: 4h after transfusion ]
Not Provided
Not Provided
 
Pilot Study About the Harmful Effects of Blood Storage on Overweight People and the Role of iNO in This Setting
Effects of Stored Red Blood Cell Transfusion in Overweight Subjects With Endothelial Dysfunction: Influence of Inhaled Nitric Oxide (iNO)
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.

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:

  1. Pulmonary vasoconstriction by trans-thoracic echocardiography
  2. Endothelium-mediated changes in vascular (arterial) tone, measured as reactive hyperemia index.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Outcomes Assessor
Primary Purpose: Basic Science
  • Blood Transfusion
  • Endothelial Physiopathology
  • Nitric Oxide
  • Pulmonary Hypertension
  • Procedure: Red blood Cells auto-transfusion
    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.
  • Procedure: Red blood Cells auto-transfusion
    Withdrawal from the same 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 40 days storage time.
  • Drug: Inhaled Nitric Oxide (iNO) administration
    Subjects will breath iNO (80ppm) for 10 minutes before, during and for one hour after the autologous old-blood transfusion.
  • Experimental: Fresh blood
    Intervention: Procedure: Red blood Cells auto-transfusion
  • Experimental: Old blood
    Intervention: Procedure: Red blood Cells auto-transfusion
  • Experimental: Old blood + inhaled Nitric Oxide
    Interventions:
    • Procedure: Red blood Cells auto-transfusion
    • Drug: Inhaled Nitric Oxide (iNO) administration

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
14
December 2013
December 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Have a photo ID
  2. Age>18 years old (required to provide informed consent)
  3. Age <60 years old
  4. Mild impairment of endothelial function, assessed by post ischemic vasodilation (L_RHI,<0.7) (38)
  5. Body mass index (BMI) >27 kg/m^2 and <40 kg/m^2
  6. Fasting during the days of transfusion.
  7. Avoiding intake of high nitrate food (i.e. green leafy vegetables: lettuce, spinach) on the day prior to the study
  8. Feel well on the day of blood donation
  9. KG within normal limits
  10. Normotensive (systolic blood pressure <140 mmHg and diastolic <90 mmHg)
  11. Normal physical exam and blood test results as indicated by:

    1. WBC 4.5-11.0 n x103/μL
    2. HGB 12.0-17.5 gm/dl
    3. PLT 150-400 n x103/μL
    4. Plasma Sodium 135-145 mmol/L
    5. Plasma Potassium 3.4-4.8 mmol/L
    6. Plasma Chloride 98-108 mmol/L
    7. Plasma Carbon Dioxide 23.0-31.9 mmol/L
    8. Plasma Urea Nitrogen 8-25 mg/dl
    9. Plasma Creatinine 0.60-1.50 mg/dl
    10. Plasma Glucose 70-110 mg/dl
    11. Transaminase-SGPT 10-55 U/L
    12. Transaminase-SGOT 10-40 U/L
    13. Total Bilirubin < 2 mg/dl
    14. Fasting plasma glucose < 110 mg/dl
    15. Methemoglobin < 3%

Exclusion Criteria:

  1. Psychiatric disturbances such as anxiety, depression, schizophrenia requiring pharmacological treatment or hospitalization in the last year
  2. Systemic disease with or without any functional limitation
  3. Pregnancy determined by urine pregnancy test, detecting presence of human chorionic gonadotropin (hCG), or less than six weeks postpartum
  4. Active smoking. Volunteers may be enrolled if they quit smoking for more than 1 year.
  5. Excess alcohol use: more than ½ L/day of wine consumption or equivalent
  6. Any current use of a medication other than: over-the-counter oral medications, herbal remedies, nutritional supplements, and oral contraceptives.
  7. Antibiotic use within 48 hours of blood donation
  8. Use of NSAIDS, corticosteroids, aspirin during the past 7 days
  9. Dental work within 24 hours prior to the donation
  10. Received or donated blood in the last 4 months
  11. Have had any forms of cancer with the exceptions of basal cell skin cancer or treatment for in situ uterine cervical cancer
  12. Currently enrolled in another research study
Sexes Eligible for Study: All
18 Years to 60 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01529502
Blood Study Overweight
Yes
Not Provided
No
Not Provided
Warren M. Zapol, Massachusetts General Hospital
Massachusetts General Hospital
Not Provided
Principal Investigator: Warren Zapol, MD Masachusetts General Hospital
Massachusetts General Hospital
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP