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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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ClinicalTrials.gov Identifier: NCT01529502
Recruitment Status : Completed
First Posted : February 8, 2012
Results First Posted : March 29, 2017
Last Update Posted : May 22, 2017
Sponsor:
Information provided by (Responsible Party):
Warren M. Zapol, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE February 6, 2012
First Posted Date  ICMJE February 8, 2012
Results First Submitted Date  ICMJE October 26, 2016
Results First Posted Date  ICMJE March 29, 2017
Last Update Posted Date May 22, 2017
Study Start Date  ICMJE March 2012
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2017)
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
Original Primary Outcome Measures  ICMJE
 (submitted: February 7, 2012)
  • 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 ]
Change History Complete list of historical versions of study NCT01529502 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2017)
Endothelial Function: Reactive Hyperemia Index [ Time Frame: Post-transfusion ]
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2012)
  • 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 ]
Current Other Pre-specified Outcome Measures
 (submitted: April 17, 2017)
  • Hemolysis [ Time Frame: before and after blood transfusion ]
    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.
  • Nitric Oxide Metabolites [ Time Frame: Before and after blood transfusion ]
    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.
  • Concentration of Cytokines [ Time Frame: Before and after blood transfusion ]
    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.
  • Activation of Platelets [ Time Frame: Before and after blood transfusion ]
    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.
  • Activation of Inflammatory Lipid Mediators [ Time Frame: Before and after blood transfusion ]
    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.
  • Changes in Gene Expression [ Time Frame: Before and after blood transfusion ]
    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.
  • Endothelial Function [ Time Frame: Before and after blood transfusion ]
    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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study About the Harmful Effects of Blood Storage on Overweight People and the Role of iNO in This Setting
Official Title  ICMJE Effects of Stored Red Blood Cell Transfusion in Overweight Subjects With Endothelial Dysfunction: Influence of Inhaled Nitric Oxide (iNO)
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:

  1. Pulmonary vasoconstriction by trans-thoracic echocardiography
  2. Endothelium-mediated changes in vascular (arterial) tone, measured as reactive hyperemia index.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE
  • Blood Transfusion
  • Endothelial Physiopathology
  • Nitric Oxide
  • Pulmonary Hypertension
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 7, 2012)
14
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01529502
Other Study ID Numbers  ICMJE Blood Study Overweight
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Warren M. Zapol, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Warren Zapol, MD Masachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date April 2017

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