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Erythropoietin and Platelet Activation Markers

Primary Purpose

Thrombosis, Hypertension

Status

Completed

Phase

Phase 4

Locations

Austria

Study Type

Interventional

Intervention

erythropoietin

About this trial

This is an interventional basic science trial for Thrombosis focused on measuring thrombosis, hypertension, gender, endothelium

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Medical University of Vienna

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Erythropoietin

Arm Description

all subjects received epo iv.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

change in erythropoietin levels

We wanted to examine erythropoietin-levels after administration of EPO at mentioned time points.

Full Information

NCT ID

NCT01392612

First Posted

July 8, 2011

Last Updated

July 13, 2011

Sponsor

Medical University of Vienna

1. Study Identification

Unique Protocol Identification Number

NCT01392612

Brief Title

Erythropoietin and Platelet Activation Markers

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2011

Overall Recruitment Status

Completed

Study Start Date

November 2006 (undefined)

Primary Completion Date

February 2007 (Actual)

Study Completion Date

July 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Medical University of Vienna

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thrombosis, Hypertension

Keywords

thrombosis, hypertension, gender, endothelium

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Erythropoietin

Arm Type

Other

Arm Description

all subjects received epo iv.

Intervention Type

Drug

Intervention Name(s)

erythropoietin

Other Intervention Name(s)

epo

Intervention Description

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.

Primary Outcome Measure Information:

Title

change in platelet activation markers

Description

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.

Time Frame

platelet activation markers were measured 4, 24, 48 and 72 hours after administration of iv EPO

Secondary Outcome Measure Information:

Title

change in erythropoietin levels

Description

We wanted to examine erythropoietin-levels after administration of EPO at mentioned time points.

Time Frame

erythropoietin levels were measured 4, 24, 48 and 72 hours after administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Wolzt, Prof.

Organizational Affiliation

Medical University of Vienna

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University of Vienna

City

Vienna

ZIP/Postal Code

1090

Country

Austria

12. IPD Sharing Statement

Citations:

PubMed Identifier

22098110

Citation

Heinisch BB, Vcelar B, Kapiotis S, Blann A, Wolzt M, Siller-Matula JM, Jilma B. The effect of erythropoietin on platelet and endothelial activation markers: a prospective trial in healthy volunteers. Platelets. 2012;23(5):352-8. doi: 10.3109/09537104.2011.631621. Epub 2011 Nov 18.

Results Reference

derived

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