Erythropoietin and Platelet Activation Markers
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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 |
- 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.
- 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 |
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 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 Vascular Diseases Cardiovascular Diseases Embolism and Thrombosis |
Epoetin Alfa Hematinics Hematologic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 16, 2013