Effects of Blood Transfusion in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Warren M. Zapol, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01226498
First received: October 14, 2010
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

The objective of this study is to assess effects of the storage of PRBC on endothelial function, inflammation and platelet activation in healthy volunteers


Condition Intervention
Blood Transfusion, Autologous
Procedure: Red blood Cells auto-transfusion

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Duration of Stored Red Blood Cell Transfusion on Physiological Parameters and Inflammatory Mediators in Healthy Adult Volunteers

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 ]
  • NO 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 ]
  • NO 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 ]
  • NO 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 ]
  • NO 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 ]
  • NO 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: 10
Study Start Date: July 2010
Study Completion Date: February 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fresh blood auto-transfusion Procedure: Red blood Cells auto-transfusion
Withdrawal from 10 Healthy volunteers of one unit of red blood cells and auto-transfusion after 3 days for one arm of the study, after 40 days for the other. Participants are enrolled in both arms of the study.
Experimental: Old blood auto-transfusion Procedure: Red blood Cells auto-transfusion
Withdrawal from 10 Healthy volunteers of one unit of red blood cells and auto-transfusion after 3 days for one arm of the study, after 40 days for the other. Participants are enrolled in both arms of the study.

Detailed Description:

The objective of this study is to assess effects of the storage of PRBC on endothelial function, inflammation and platelet activation in healthy volunteers.

The present study consists of two parts. During one phase of the study, 10 healthy human volunteers will donate a unit of blood, which will be leukoreduced and stored in Additive Solutions-1 (AS-1), and then transfused back to the subjects after 2 days of storage at 4º C in the MGH Blood Bank. The other part of the study consists in the collection of a unit of blood from the same volunteers, but which will be transfused back to the same subject after 40 days of storage. There will be a break of 2 week period in between these 2 study phases. The order of these 2 study parts will be randomized.

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 2 days with the response to PRBC stored for 40 days in the same healthy volunteers. 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 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Have a photo ID
  • Body mass index (BMI) <25 kg/m2 and >18 kg/m2
  • Fasting for 8 hours prior to enrollment in the study (a sip of water or brushing teeth in the morning are allowed)
  • Feel well the day of blood donation
  • Normal physical exam and normal blood test as indicated:
  • WBC 4.5-11.0 th/cmm
  • HGB 12.5-17.5 gm/dl
  • PLT 150-400 th/cumm
  • 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

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
  • controlled hypertension
  • controlled diabetes without systemic effects
  • 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 cervical cancer
  • 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: NCT01226498

Locations
United States, Massachusetts
Massachusetts General Hospital (MGH)
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Warren M Zapol, MD Massachusetts General Hospital, DACCPM
  More Information

Publications:
Responsible Party: Warren M. Zapol, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01226498     History of Changes
Other Study ID Numbers: 2010P000961
Study First Received: October 14, 2010
Last Updated: January 29, 2014
Health Authority: 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

ClinicalTrials.gov processed this record on August 21, 2014