Erythropoietin and Platelet Activation Markers

Hypertension Clinical Trial

Official title:

The Effect of Erythropoietin on Platelet Activation Markers: a Prospective Study in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01392612
• Other study ID #: EPO1
• Status: Completed
• Phase: Phase 4
• First received: July 8, 2011
• Last updated: July 13, 2011
• Start date: November 2006
• Est. completion date: July 2007

Study information

• Verified date: July 2011
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial Summary

We hypothesized that the effect of erythropoietin may be reflected by changes in thromboxane B2 (TXB2) and endothelial cell function.

Six male and six female subjects received recombinant human epoetin alpha (Erypo®) intravenously (300 Units per kg). Biomarker levels were assessed at baseline and 4, 24, 48 and 72 hours after administration.

Description:

Introduction: Erythropoietin (EPO) enhances formation of red blood cells and also affects thrombopoiesis and platelet function. We hypothesized that the effect of erythropoietin may be reflected by changes in thromboxane B2 (TXB2) and endothelial cell function.

Methods: Six male and six female subjects received recombinant human epoetin alpha (Erypo®) intravenously (300 Units per kg). Biomarker levels were assessed at baseline and 4, 24, 48 and 72 hours after administration.

Results: Epoetin alpha increased TXB2 levels, which reached significance at 48h (2.5- fold increase: 6.6±5ng/mL vs. 15±9ng/mL; p=0.044) and remained at that level at 72h. In line, epoetin alpha increased E-selectin levels by 25% already at 24h (39±21ng/ml vs. 49±26ng/ml; p<0.001) and stayed at this level until 72h (p<0.001). The raise in platelet activation markers corresponded with a 2-fold increase in reticulocyte count (81±17G/L vs. 43±10G/L; p<0.001) and a 9% increase in platelet count at 72h (224±45G/L vs. 244±52G/L; p=0.005). Thrombomodulin and von Willebrand factor concentrations were not significantly altered by epoetin alpha. Interestingly, gender differences in the baseline levels of E-selectin and thrombomodulin were observed. E-selectin and thrombomodulin levels were doubled in men compared to women (51±24ng/mL and 28±10ng/mL; p=0.025 and 30±5ng/mL vs. 16±5ng/mL; p=0.002, respectively).

Conclusion: Epoetin alpha increases levels of platelet activation markers. Further studies are needed to investigate whether measurement of TXB2 or E-selectin levels might be useful for estimation of thromboembolic risk during EPO-therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy male and female volunteers.

• Age between 18-40 years.

• Body mass index 17-27.

• Normal haemoglobin levels (Hb males 13.5-18g/dL, females 12-16g/dL).

• Reticulocyte count within reference values (32-110G/L).

• S-Iron within reference values (males 60-150µg/dl, females 40-150µg/dL).

• Serum ferritin within reference values (females 10-140µg/L, males 20-280µg/L).

• CRP within reference values (<1,0mg/dL).

• Signed informed consent.

• Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant for this study.

• Woman of child bearing potential must agree to practice effective barrier methods for birth control.

Exclusion Criteria:

• Smoking.

• Regular use of medication and food supplements containing iron.

• Abuse of alcoholic beverages and drugs.

• Participation in a clinical trial in the 3 weeks preceding the study.

• Foreseen inability to attend to scheduled study visits.

• Deficiency in folate (<3.4nmol/L) or vitamin B12 (<118pmol/L) (reevaluation after supplementation is allowed).

• Evidence of hypertension, pathologic hyperglycemia, hyperlipidemia. AST and/or ALAT > 3xULN (AST males > 105U/L, females >93U/; ALAT males > 135U/L, females >102U/L).

• Symptoms of a clinically relevant illness during 3 weeks prior the first study day.

• History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of erythropoietin.

• Blood donation during the previous 3 weeks prior to the first study day.

• History of hypersensitivity erythropoietin.

• Pregnancy or lactation period.

• Any medical condition that, in the opinion of the investigator, would interfere with safety of the subject or interference of the objectives of the study.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hypertension
• Thrombosis

Intervention

Drug:
• erythropoietin
Subjects received one single intravenous injection of epoetin alpha (Erypo®, rhEPO, Ortho Biotech/Division of Janssen-Cilag Ag, Bridgewater, New Jersey, US) at a dose of 300 Units per kg bodyweight. Blood was sampled at baseline and 4, 24, 48 and 72 hours after administration of rhEPO during a biosimilarity trial.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in platelet activation markers	We wanted to examine whether levels of platelet activation markers change after administration of EPO and if they do, in which time frame it happens.	platelet activation markers were measured 4, 24, 48 and 72 hours after administration of iv EPO	No
Secondary	change in erythropoietin levels	We wanted to examine erythropoietin-levels after administration of EPO at mentioned time points.	erythropoietin levels were measured 4, 24, 48 and 72 hours after administration	No