Erythropoietin and Platelet Activation Markers

This study has been completed.
Sponsor:
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01392612
First received: July 8, 2011
Last updated: July 13, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Thrombosis
Hypertension
Drug: erythropoietin
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Effect of Erythropoietin on Platelet Activation Markers: a Prospective Study in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • change in platelet activation markers [ Time Frame: platelet activation markers were measured 4, 24, 48 and 72 hours after administration of iv EPO ] [ Designated as safety issue: No ]
    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 [ Time Frame: erythropoietin levels were measured 4, 24, 48 and 72 hours after administration ] [ Designated as safety issue: No ]
    We wanted to examine erythropoietin-levels after administration of EPO at mentioned time points.


Enrollment: 12
Study Start Date: November 2006
Study Completion Date: July 2007
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Erythropoietin
all subjects received epo iv.
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.
Other Name: epo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01392612

Locations
Austria
Medical University of Vienna
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Michael Wolzt, Prof. Medical University of Vienna
  More Information

No publications provided by Medical University of Vienna

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Department of Clinical Pharmacology, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01392612     History of Changes
Other Study ID Numbers: EPO1
Study First Received: July 8, 2011
Last Updated: July 13, 2011
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
thrombosis
hypertension
gender
endothelium

Additional relevant MeSH terms:
Hypertension
Thrombosis
Cardiovascular Diseases
Embolism and Thrombosis
Vascular Diseases
Epoetin alfa
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014