Clinical trial NCT01226498: Effects of Blood Transfusion in Healthy Volunteers
Official title: Effects of Duration of Stored Red Blood Cell Transfusion on Physiological Parameters and Inflammatory Mediators in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Blood Transfusion, Autologous
Keywords: Blood Transfusion, Autologous
Blood Preservation/adverse effects
Blood Transfusion/adverse effects
Endothelium, Vascular/physiopathology
Inflammation Mediators
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2010-10-22
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

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 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

Primary outcomes:
measure: Endothelial function
timeFrame: Baseline
measure: Endothelial function
timeFrame: 10 min after transfusion
measure: Endothelial function
timeFrame: 1h after transfusion
measure: Endothelial function
timeFrame: 4h after transfusion
Secondary outcomes:
measure: Hemolysis
timeFrame: Baseline
measure: NO metabolites
timeFrame: Baseline
measure: Concentration of cytokines
timeFrame: Baseline
measure: Activation of platelets
timeFrame: Baseline
measure: Activation of inflammatory lipid mediators
timeFrame: Baseline
measure: Changes in gene expression
timeFrame: Baseline
measure: Hemolysis
timeFrame: 10 min after transfusion
measure: NO metabolites
timeFrame: 10 min after transfusion
measure: Concentration of cytokines
timeFrame: 10 min after transfusion
measure: Activation of platelets
timeFrame: 10 min after transfusion
measure: Activation of inflammatory lipid mediators
timeFrame: 10 min after transfusion
measure: Changes in gene expression
timeFrame: 10 min after transfusion
measure: Hemolysis
timeFrame: 1h after transfusion
measure: NO metabolites
timeFrame: 1h after transfusion
measure: Concentration of cytokines
timeFrame: 1h after transfusion
measure: Activation of platelets
timeFrame: 1h after transfusion
measure: Activation of inflammatory lipid mediators
timeFrame: 1h after transfusion
measure: Changes in gene expression
timeFrame: 1h after transfusion
measure: Hemolysis
timeFrame: 2h after transfusion
measure: NO metabolites
timeFrame: 2h after transfusion
measure: Concentration of cytokines
timeFrame: 2h after transfusion
measure: Activation of platelets
timeFrame: 2h after transfusion
measure: Activation of inflammatory lipid mediators
timeFrame: 2h after transfusion
measure: Changes in gene expression
timeFrame: 2h after transfusion
measure: Hemolysis
timeFrame: 4h after transfusion
measure: NO metabolites
timeFrame: 4h after transfusion
measure: Concentration of cytokines
timeFrame: 4h after transfusion
measure: Activation of platelets
timeFrame: 4h after transfusion
measure: Activation of inflammatory lipid mediators
timeFrame: 4h after transfusion
measure: Changes in gene expression
timeFrame: 4h after transfusion
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH)
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital, DACCPM
name: Warren M Zapol, MD
role: PRINCIPAL_INVESTIGATOR
References:
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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.
citation: Gladwin MT, Lancaster JR Jr, Freeman BA, Schechter AN. Nitric oxide's reactions with hemoglobin: a view through the SNO-storm. Nat Med. 2003 May;9(5):496-500. doi: 10.1038/nm0503-496. No abstract available.
citation: Nagasaka Y, Fernandez BO, Garcia-Saura MF, Petersen B, Ichinose F, Bloch KD, Feelisch M, Zapol WM. Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury. Anesthesiology. 2008 Oct;109(4):675-82. doi: 10.1097/ALN.0b013e318186316e.