Effects of Blood Transfusion in Healthy Volunteers

Blood Transfusion, Autologous Clinical Trial

Official title:

Effects of Duration of Stored Red Blood Cell Transfusion on Physiological Parameters and Inflammatory Mediators in Healthy Adult Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01226498
• Other study ID #: 2010P000961
• Status: Completed
• Phase: N/A
• First received: October 14, 2010
• Last updated: January 29, 2014
• Start date: July 2010
• Est. completion date: February 2011

Study information

• Verified date: January 2014
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: February 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Blood Transfusion, Autologous

Intervention

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.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital (MGH)	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (7)

Bennett-Guerrero E, Veldman TH, Doctor A, Telen MJ, Ortel TL, Reid TS, Mulherin MA, Zhu H, Buck RD, Califf RM, McMahon TJ. Evolution of adverse changes in stored RBCs. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17063-8. Epub 2007 Oct 11. — View Citation

Cardillo C, Kilcoyne CM, Cannon RO 3rd, Panza JA. Interactions between nitric oxide and endothelin in the regulation of vascular tone of human resistance vessels in vivo. Hypertension. 2000 Jun;35(6):1237-41. — View 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. Review. — View Citation

Hendrickson JE, Hillyer CD. Noninfectious serious hazards of transfusion. Anesth Analg. 2009 Mar;108(3):759-69. doi: 10.1213/ane.0b013e3181930a6e. Review. — View Citation

Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, Blackstone EH. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008 Mar 20;358(12):1229-39. doi: 10.1056/NEJMoa070403. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endothelial function		Baseline	No
Primary	Endothelial function		10 min after transfusion	No
Primary	Endothelial function		1h after transfusion	No
Primary	Endothelial function		4h after transfusion	No
Secondary	Hemolysis		Baseline	No
Secondary	NO metabolites		Baseline	No
Secondary	Concentration of cytokines		Baseline	No
Secondary	Activation of platelets		Baseline	No
Secondary	Activation of inflammatory lipid mediators		Baseline	No
Secondary	Changes in gene expression		Baseline	No
Secondary	Hemolysis		10 min after transfusion	No
Secondary	NO metabolites		10 min after transfusion	No
Secondary	Concentration of cytokines		10 min after transfusion	No
Secondary	Activation of platelets		10 min after transfusion	No
Secondary	Activation of inflammatory lipid mediators		10 min after transfusion	No
Secondary	Changes in gene expression		10 min after transfusion	No
Secondary	Hemolysis		1h after transfusion	No
Secondary	NO metabolites		1h after transfusion	No
Secondary	Concentration of cytokines		1h after transfusion	No
Secondary	Activation of platelets		1h after transfusion	No
Secondary	Activation of inflammatory lipid mediators		1h after transfusion	No
Secondary	Changes in gene expression		1h after transfusion	No
Secondary	Hemolysis		2h after transfusion	No
Secondary	NO metabolites		2h after transfusion	No
Secondary	Concentration of cytokines		2h after transfusion	No
Secondary	Activation of platelets		2h after transfusion	No
Secondary	Activation of inflammatory lipid mediators		2h after transfusion	No
Secondary	Changes in gene expression		2h after transfusion	No
Secondary	Hemolysis		4h after transfusion	No
Secondary	NO metabolites		4h after transfusion	No
Secondary	Concentration of cytokines		4h after transfusion	No
Secondary	Activation of platelets		4h after transfusion	No
Secondary	Activation of inflammatory lipid mediators		4h after transfusion	No
Secondary	Changes in gene expression		4h after transfusion	No