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: January 29, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Blood Transfusion
Endothelial Physiopathology
Inflammation
Hemoglobins
Nitric Oxide
Procedure: Red blood Cells auto-transfusion
Drug: Inhaled Nitric Oxide (iNO) administration
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Stored Red Blood Cell Transfusion in Overweight Subjects With Endothelial Dysfunction: Influence of Inhaled Nitric Oxide (iNO)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Endothelial Function [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Endothelial Function [ Time Frame: 10 min after transfusion ] [ Designated as safety issue: No ]
  • Endothelial function [ Time Frame: 1h after transfusion ] [ Designated as safety issue: No ]
  • Endothelial Function [ Time Frame: 4h after transfusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hemolysis [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Nitric Oxide metabolites [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Concentration of cytokines [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Activation of platelets [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Activation of inflammatory lipid mediators [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Changes in gene expression [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Hemolysis [ Time Frame: 10 min after transfusion ] [ Designated as safety issue: No ]
  • Nitric Oxide Metabolites [ Time Frame: 10 min after transfusion ] [ Designated as safety issue: No ]
  • Concentration of cytokines [ Time Frame: 10 min after transfusion ] [ Designated as safety issue: No ]
  • Activation of platelets [ Time Frame: 10 min after transfusion ] [ Designated as safety issue: No ]
  • Activation of inflammatory lipid mediators [ Time Frame: 10 min after transfusion ] [ Designated as safety issue: No ]
  • Changes in gene expression [ Time Frame: 10 min after transfusion ] [ Designated as safety issue: No ]
  • Hemolysis [ Time Frame: 1h after transfusion ] [ Designated as safety issue: No ]
  • Nitric Oxide metabolites [ Time Frame: 1h after transfusion ] [ Designated as safety issue: No ]
  • Concentration of cytokines [ Time Frame: 1h after transfusion ] [ Designated as safety issue: No ]
  • Activation of platelets [ Time Frame: 1h after transfusion ] [ Designated as safety issue: No ]
  • Activation of inflammatory lipid mediators [ Time Frame: 1h after transfusion ] [ Designated as safety issue: No ]
  • Changes in gene expression [ Time Frame: 1h after transfusion ] [ Designated as safety issue: No ]
  • Hemolysis [ Time Frame: 2h after transfusion ] [ Designated as safety issue: No ]
  • Nitric Oxide metabolites [ Time Frame: 2h after transfusion ] [ Designated as safety issue: No ]
  • Concentration of cytokines [ Time Frame: 2h after transfusion ] [ Designated as safety issue: No ]
  • Activation of platelets [ Time Frame: 2h after transfusion ] [ Designated as safety issue: No ]
  • Activation of inflammatory lipid mediators [ Time Frame: 2h after transfusion ] [ Designated as safety issue: No ]
  • Changes in gene expression [ Time Frame: 2h after transfusion ] [ Designated as safety issue: No ]
  • Hemolysis [ Time Frame: 4h after transfusion ] [ Designated as safety issue: No ]
  • Nitric Oxide metabolites [ Time Frame: 4h after transfusion ] [ Designated as safety issue: No ]
  • Concentration of cytokines [ Time Frame: 4h after transfusion ] [ Designated as safety issue: No ]
  • Activation of platelets [ Time Frame: 4h after transfusion ] [ Designated as safety issue: No ]
  • Activation of inflammatory lipid mediators [ Time Frame: 4h after transfusion ] [ Designated as safety issue: No ]
  • Changes in gene expression [ Time Frame: 4h after transfusion ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: March 2012
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fresh blood 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.
Experimental: Old blood 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.
Experimental: Old blood + inhaled Nitric Oxide 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.

Detailed 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
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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/m2 and <35 kg/m2
  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01529502

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Warren Zapol, MD Masachusetts General Hospital
  More Information

Publications:
Responsible Party: Warren M. Zapol, Emeritus Anesthetist-in-Chief and Director of the MGH Anesthesia Center for Critical Care Research, Massachusetts General Hospital; Reginald Jenney Professor of Anesthesia, Harvard Medical School, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01529502     History of Changes
Other Study ID Numbers: Blood Study Overweight
Study First Received: February 6, 2012
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Blood Transfusion, Autologous
Blood Preservation/adverse effects
Blood Transfusion/adverse effects
Endothelium, Vascular/physiopathology
Inflammation Mediators
Hemoglobins
Nitric Oxide

Additional relevant MeSH terms:
Inflammation
Overweight
Pathologic Processes
Body Weight
Signs and Symptoms
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Gasotransmitters
Protective Agents

ClinicalTrials.gov processed this record on September 18, 2014